Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication

Abstract

Significance
We present highlights of the first complete domestic cat reference genome, to our knowledge. We provide evolutionary assessments of the feline protein-coding genome, population genetic discoveries surrounding domestication, and a resource of domestic cat genetic variants. These analyses span broadly, from carnivore adaptations for hunting behavior to comparative odorant and chemical detection abilities between cats and dogs. We describe how segregating genetic variation in pigmentation phenotypes has reached fixation within a single breed, and also highlight the genomic differences between domestic cats and wildcats. Specifically, the signatures of selection in the domestic cat genome are linked to genes associated with gene knockout models affecting memory, fear-conditioning behavior, and stimulus-reward learning, and potentially point to the processes by which cats became domesticated.

Full text

Comparative analysis of the domestic cat genome
reveals genetic signatures underlying feline
biology and domestication
Michael J. Montague
a,1
, Gang Li
b,1
, Barbara Gandolfi
c
, Razib Khan
d
, Bronwen L. Aken
e
, Steven M. J. Searle
e
,
Patrick Minx
a
, LaDeana W. Hillier
a
, Daniel C. Koboldt
a
, Brian W. Davis
b
, Carlos A. Driscoll
f
, Christina S. Barr
f
,
Kevin Blackistone
f
, Javier Quilez
g
, Belen Lorente-Galdos
g
, Tomas Marques-Bonet
g,h
, Can Alkan
i
, Gregg W. C. Thomas
j
,
Matthew W. Hahn
j
, Marilyn Menotti-Raymond
k
, Stephen J. O’Brien
l,m
, Richard K. Wilson
a
, Leslie A. Lyons
c,2
,
William J. Murphy
b,2
, and Wesley C. Warren
a,2
a
The Genome Institute, Washington University School of Medicine, St. Louis, MO 63108;
b
Department of Veterinary Integrative Biosciences, College of
Veterinary Medicine, Texas A&M University, College Station, TX 77843;
c
Department of Veterinary Medicine & Surgery, College of Veterinary Medicine,
University of Missouri, Columbia, MO 65201;
d
Population Health & Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616;
e
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
f
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health,
Bethesda, MD 20886;
g
Catalan Institution for Research and Advanced Studies, Institute of Evolutionary Biology, Pompeu Fabra University, 08003
Barcelona, Spain;
h
Centro de Analisis Genomico 08028, Barcelona, Spain;
i
Department of Computer Engineering, Bilkent University, Ankara 06800, Turkey;
j
Department of Biology, Indiana University, Bloomington, IN 47405;
k
Laboratory of Genomic Diversity, Center for Cancer Research, Frederick, MD 21702;
l
Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199178, Russia; and
m
Oceanographic Center, Nova
Southeastern University, Fort Lauderdale, FL 33314
Edited by James E. Womack, Texas A&M University, College Station, TX, and approved October 3, 2014 (received for review June 2, 2014)
Little is known about the genetic changes that distinguish
domestic cat populations from their wild progenitors. Here we
describe a high-quality domestic cat reference genome assembly
and comparative inferences made with other cat breeds, wildcats,
and other mammals. Based upon these comparisons, we identified
positively selected genes enriched for genes involved in lipid
metabolism that underpin adaptations to a hypercarnivorous diet.
We also found positive selection signals within genes underlying
sensory processes, especially those affecting vision and hearing in the
carnivore lineage. We observed an evolutionary tradeoff between
functional olfactory and vomeronasal receptor gene repertoires in the
cat and dog genomes, with an expansion of the feline chemosensory
system for detecting pheromones at the expense of odorant de-
tection. Genomic regions harboring signatures of natural selection
that distinguish domestic cats from their wild congeners are enriched
in neural crest-related genes associated with behavior and reward in
mouse models, as predicted by the domestication syndrome hypoth-
esis. Our description of a previously unidentified allele for the gloving
pigmentation pattern found in the Birman breed supports the hy-
pothesis that cat breeds experienced strong selection on specific
mutations drawn from random bred populations. Collectively, these
findings provide insight into how the process of domestication altered
the ancestral wildcat genome and build a resource for future disease
mapping and phylogenomic studies across all members of the Felidae.
Felis catus
|
domestication
|
genome
The domestic cat (Felis silvestris catus) is a popular pet species,
with as many as 600 million individuals worldwide (1). Cats
and other members of Carnivora last shared a common ancestor
with humans ∼92 million years ago (2, 3). The cat family Felidae
includes ∼38 species that are widely distributed across the world,
inhabiting diverse ecological niches that have resulted in di-
vergent morphological and behavioral adaptations (4). The
earliest archaeological evidence for human coexistence with cats
dates to ∼9.5 kya in Cyprus and ∼5 kya in central China (5, 6),
during periods when human populations adopted more agricul-
tural lifestyles. Given their sustained beneficial role surrounding
vermin control since the human transition to agriculture, any
selective forces acting on cats may have been minimal sub-
sequent to their domestication. Unlike many other domesticated
mammals bred for food, herding, hunting, or security, most of
the 30–40 cat breeds originated recently, within the past 150 y,
largely due to selection for aesthetic rather than functional traits.
Previous studies have assessed breed differentiation (6, 7),
phylogenetic origins of the domestic cat (8), and the extent of
recent introgression between domestic cats and wildcats (9, 10).
However, little is known regarding the impact of the domesti-
cation process within the genomes of modern cats and how this
compares with genetic changes accompanying selection identified in
other domesticated companion animal species. Here we describe, to
our knowledge, the first high-quality annotation of the complete
Significance
We present highlights of the first complete domestic cat reference
genome, to our knowledge. We provide evolutionary assessments
of the feline protein-coding genome, population genetic discoveries
surrounding domestication, and a resource of domestic cat genetic
variants. These analyses span broadly, from carnivore adaptations
for hunting behavior to comparative odorant and chemical de-
tection abilities between cats and dogs. We describe how segre-
gating genetic variation in pigmentation phenotypes has reached
fixation within a single breed, and also highlight the genomic dif-
ferences between domestic cats and wildcats. Specifically, the sig-
natures of selection in the domestic cat genome are linked to genes
associated with gene knockout models affecting memory, fear-
conditioning behavior, and stimulus-reward learning, and poten-
tially point to the processes by which cats became domesticated.
Author contributions: M.J.M., G.L., B.G., L.A.L., W.J.M., and W.C.W. designed research;
M.J.M., G.L., B.G., P.M., L.W.H., D.C.K., B.W.D., C.A.D., C.S.B., K.B., G.W.C.T., M.W.H., M.M.-R.,
S.J.O., L.A.L., W.J.M., and W.C.W. performed research; M.J.M., G.L., B.G., B.L.A., S.M.J.S.,
D.C.K., B.W.D., C.A.D., J.Q., B.L.-G., T.M.-B., C.A., G.W.C.T., M.W.H., R.K.W., L.A.L., W.J.M.,
and W.C.W. contributed new reagents/analytic tools; M.J.M., G.L., B.G., R.K., B.W.D., J.Q.,
B.L.-G., T.M.-B., C.A., G.W.C.T., M.W.H., L.A.L., W.J.M., and W.C.W. analyzed data; and
M.J.M., G.L., B.G., R.K., P.M., D.C.K., B.W.D., C.A.D., C.S.B., K.B., T.M.-B., M.W.H., L.A.L.,
W.J.M., and W.C.W. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The sequences reported in this paper have been deposited in the Gen-
Bank database (accession nos. GU270865.1,KJ923925–KJ924979,SRX026946,SRX026943,
SRX026929,SRX027004,SRX026944,SRX026941,SRX026909,SRX026901,SRX026955,
SRX026947,SRX026911,SRX026910,SRX026948,SRX026928,SRX026912,SRX026942,
SRX026930,SRX026913,SRX019549,SRX019524,SRX026956,SRX026945,andSRX026960).
1
M.J.M. and G.L. contributed equally to this work.
2
To whom correspondence may be addressed. Email: wwarren@genome.wustl.edu,
wmurphy@cvm.tamu.edu, or lyonsla@missouri.edu.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.
1073/pnas.1410083111/-/DCSupplemental.
www.pnas.org/cgi/doi/10.1073/pnas.1410083111 PNAS Early Edition
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GENETICS

domestic cat genome and a comparative genomic analysis including
whole-genome sequences from other felids and mammals to identify
the molecular footprints of the domestication process within cats.
Results and Discussion
To identify molecular signatures underlying felid phenotypic inno-
vations, we developed a higher-quality reference assembly for the
domestic cat genome using whole-genome shotgun sequences
(Materials and Methods and SI Materials and Methods). The as-
sembly (FelCat5) comprises 2.35 gigabases (Gb) assigned to all 18
autosomes and the X chromosome relying on physical and linkage
maps (11) with a further 11 megabases (Mb) in unplaced scaffolds.
The assembly is represented by an N50 contig length of 20.6 kb and
a scaffold N50 of 4.7 Mb, both of which show substantial im-
provement over previous light-coverage genome survey sequences
that included only 60% of the genome (12, 13). The Felis catus
genome is predicted to contain 19,493 protein-coding genes and
1,855 noncoding RNAs, similar to dog (14). Hundreds of feline
traits and disease pathologies (15) offer novel opportunities to ex-
plore the genetic basis of simple and complex traits, host suscepti-
bility to infectious diseases, as well as the distinctive genetic changes
accompanying the evolution of carnivorans from other mammals.
To identify signatures of natural selection along the lineages
leading to the domestic cat, we identified rates of evolution using
genome-wide analyses of the ratio of divergence at nonsynonymous
and synonymous sites (d
N
/d
S
)(16)(Materials and Methods and
SI Materials and Methods). We used the annotated gene set (19,493
protein-coding genes) to compare unambiguous mammalian gene
orthologs shared between cat, tiger, dog, cow, and human (n=10,317).
Two-branch and branch-site models (17) collectively identified 467,
331, and 281 genes that were putatively shaped by positive selection
in the carnivore, felid, and domestic cat (subfamily Felinae) an-
cestral lineages, respectively (S1.1–S1.3 in Dataset S1). We assessed
the potential impact of amino acid changes using TreeSAAP (18)
and PROVEAN (19). The majority of identified genes possess
substitutions with significant predicted structural or biochemical
effects based on one or both tests (Fig. S1 and S1.4 in Dataset S1).
Although the inferences produced by our methods call for addi-
tional functional analyses, we highlight several positively selected
genes to illustrate their importance to carnivore and feline biology.
Carnivores are endowed with extremely acute sensory adap-
tations, allowing them to effectively locate potential prey before
being discovered (20). Within carnivores, cats have the broadest
hearing range, allowing them to detect both ultrasonic commu-
nication by prey as well as their movement (21). We identified six
positively selected genes (Fig. 1) that conceivably evolved to
increase auditory acuity over a wider range of frequencies in the
carnivore ancestor and within Felidae, as mutations within each
gene have been associated with autosomal, nonsyndromic deaf-
ness or hearing loss (22, 23). Visual acuity is adaptive for hunting
and catching prey, especially for crepuscular predators such as
the cat and other carnivores. Accordingly, we identified elevated
d
N
/d
S
values for 20 carnivoran genes that, when mutated in
humans, have well-described roles in a spectrum of visual pa-
thologies (Fig. 1). For example, truncating mutations in human
CHM cause the progressive disease choroideremia (24), begin-
ning with a loss of night vision and peripheral vision and later
a loss of central vision. Many carnivores have excellent night
vision (20, 25), and we postulate that the acquisition of selec-
tively advantageous amino acid substitutions within several genes
increased visual acuity under low-light conditions. In one in-
teresting dual-role example, MYO7A encodes a protein involved
in the maintenance of both auditory and visual systems that,
when mutated, results in loss of hearing and vision (26).
Cats differ from most other carnivores as a result of being ob-
ligately carnivorous. One outcome of this adaptive process is that
cats are unable to synthesize certain essential fatty acids, spe-
cifically arachidonic acid, due to low Delta-6-desaturase activity
(27). This has led to suggestions that cats use an alternate (yet
unknown) pathway to generate this essential fatty acid for normal
health and reproduction. Furthermore, cats fed a diet rich in
saturated and polyunsaturated fatty acids showed no effects on
plasma lipid concentrations that in humans are risk factors for
coronary heart disease and atherosclerosis (28). These aspects of
feline biology are reflected in our positive selection results, where
the notable classes of genes overrepresented in the Felinae list
Fig. 1. Dynamic evolution of feline sensory repertoires (Upper). The phy-
logenetic tree depicts relationships scaled to time between dog, tiger, and
domestic cat. Positively selected genes are listed (Top Right), with lines in-
dicating genes identified on the ancestral branch of Carnivora (Top), Felidae
(Middle), and Felinae (Bottom). Genes highlighted in red and orange were
identified with significant structural or biochemical effects by two tests or one
test, respectively (S1.4 in Dataset S1). MYO7A (*) expression is associated
with hearing and vision. Numbers at each tree node represent the recon-
structed ancestral functional olfactory receptor gene (Or) repertoire for carni-
vores and felids. Numbers labeling each branch are estimated Or gene gain
(green) and loss (red). The pie charts refer to functional and nonfunctional
(pseudogenic) vomeronasal (V1r;Top)andOr (Bottom) gene repertoires, with
circles drawn in proportion to the size of each gene repertoire. Or genes are
depicted in blue (functional) and red (nonfunctional), and V1r genes are depic-
ted in green (functional) and yellow (nonfunctional). Beneath each pie chart are
numbers of functional/nonfunctional/total genes identified in the current ge-
nome annotations of the three species. Bar graphs depict rates of Or gene gain
and loss. Location of signatures of positive selection (Lower). Several genes en-
code members of the myosin gene family of mechanochemical proteins, with
MYO15A notably under selection in all three branches tested. Curved lines
represent the estimated d
N
/d
S
values (yaxis) calculated in 90-bp sliding windows
(step size of 18 bp) along the length of the gene alignment (xaxis) for dog, cat,
and tiger. Colored boxes indicate known functional domains. Arrowheads in-
dicate the location of positively selected amino acid sites based on the results of
the branch-site test. Stars indicate deleterious mutations in the domestic cat
(Materials and Methods). Motifs and domains include the IQ calmodulin-binding
motif (IQ); the myosin tail homology 4 domain (MyTH4); the FERM domain
(FERM); the SRC homology 3 domain (SH3); and the PDZ domain (PDZ).
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are related to lipid metabolism (S1.5 in Dataset S1). For exam-
ple, one of the positively selected genes, ACOX2, is critical for
metabolism of branch-chain fatty acids and has been suggested to
regulate triglyceride levels (29), whereas mutations in PAFAH2
have been associated with risk for coronary heart disease and is-
chemia (30). The enrichment of genes related to lipid metabolism
is likely a signature of adaptation for accommodating the hyper-
carnivorous diet of felids (31), and mirrors similar signs of selection
on lipid metabolic pathways in the genomes of polar bears (32).
Gene duplication and gene loss events often play substantial
roles in phenotypic differences between species. To identify
protein families that rapidly evolved in the domestic cat, either
by contraction or expansion, we examined gene family expansion
along an established species tree (33) using tree orthology (34).
Two extensive chemosensory gene families, coding for olfactory
(Or) and vomeronasal (V1r) receptors, are responsible for small-
molecule detection of odorants and other chemicals for medi-
ating pheromone perception, respectively. Cats rely less on smell
to hunt and locate prey in comparison with dogs, which are well-
known for their olfactory prowess (35). These observations are
confirmed by our analysis of the complete Or gene repertoires for
cat, tiger, and dog (Fig. 1), illustrating smaller functional reper-
toires in felids relative to dogs (∼700 genes versus >800, respec-
tively). By contrast, the V1r gene repertoire is markedly reduced
in dogs but expanded in the ancestor of the cat family (8 versus
21 functional genes, respectively), with evidence for species-specific
gene loss in different felids (Fig. 1 and Figs. S2 and S3). A growing
body of evidence cataloging Or gene repertoires in diverse mammals
demonstrates common tradeoffs between functional Or reper-
toire size and other sensory systems involved in ecological niche
specialization, such as loss of Or genes coinciding with gains in
trichromatic color vision in primates (36) and chemosensation in
platypus (37). These results add further evidence supporting cats’
extensive reliance on pheromones for sociochemical communi-
cation (38), which is consistent with a genomic tradeoff between
functional Or and V1r repertoires in response to uniquely evolved
ecological strategies in the canid and felid lineages (4).
Cats are considered only a semidomesticated species, because
many populations are not isolated from wildcats and humans do
not control their food supply or breeding (39, 40). We therefore
predicted a relatively modest effect of domestication on the cat
genome based on recent divergence from and ongoing admixture
with wildcats (8–10), a relatively short human cohabitation time
compared with dogs (5, 6), and the lack of clear morphological
and behavioral differences from wildcats, with docility, gracility, and
pigmentation being the exceptions. To identify genomic regions
showing signatures of selection influenced by the domestication
process, we used whole-genome analyses of cats from different
domestic breeds and wildcats (i.e., other F. silvestris subspecies) using
pooling methods that control for genetic drift (41). Detecting the
genomic regions under putative selection during cat domestica-
tion can be complicated by random fixation due to genetic drift
during the formation of breeds. We mitigated this effect by com-
bining sequence data from a collection of 22 cats (∼58×coverage)
from six phylogenetically and geographically dispersed domestic
breeds (42) before variant detection and performed selection
analyses relative to variants detected within a pool of European
(F. silvestris silvestris) and Near Eastern (F. silvestris lybica)
wildcats (∼7×coverage; Figs. S4 and S5 and S2.1 in Dataset S2).
After stringent filtering of resequencing data, we aligned sequen-
ces to the cat reference genome and identified 8,676,486 and
5,190,430 high-quality single-nucleotide variants (SNVs) among
domestic breeds and wildcats, respectively, at a total of 10,975,197
sites (Fig. S3). We next identified 130 regions along cat autosomes
with either pooled heterozygosity (H
p
) 4 SDs below the mean or
divergence (F
ST
) greater than 4 SDs from the mean (Figs. S4 and
S6,SI Materials and Methods, and S2.2 and S2.3 in Dataset S2).
After parsing regions of high confidence displaying both low
domestic H
p
and high F
ST
, we found 13 genes underlying five
chromosomal regions (Fig. 2, Fig. S4, and S2.4 in Dataset S2).
Genes within each of these regions play important roles in neural
processes, notably pathways related to synaptic circuitry that in-
fluence behavior and contextual clues related to reward.
One putative region of selection along chromosome A1
(chrA1) (Fig. 3) is denoted by a pair of protocadherin genes
(PCDHA1 and PCDHB4), which establish and maintain specific
neuronal connections and have implications for synaptic speci-
ficity, serotonergic innervation of the brain, and fear condition-
ing (43). PCDHB4 was also identified in the d
N
/d
S
analyses. A
second region, also on chrA1 (Fig. 3), overlaps with a glutamate
receptor gene, GRIA1. Glutamate receptors are the predominant
excitatory neurotransmitter receptors in the mammalian brain and
play an important role in the expression of long-term potenti-
ation and memory formation (44). GRIA1 knockout mice ex-
hibit defects in stimulus-reward learning, notably those related
to food rewards (45). Two additional glutamate receptor genes,
Fig. 2. Sliding window analyses identify five regions of putative selection in the domestic cat genome. Measurements of Z-transformed pooled heterozy-
gosity in cat [inner plot; Z(H
p
)] and the Z-transformed fixation index between pooled domestic cat and pooled wildcat [outer plot; Z(F
ST
)] for autosomal 100-kb
windows across all 18 autosomes (Left). Red points indicate windows that passed the threshold for elevated divergence [>4Z(F
ST
)] or low diversity [<4Z(H
P
)].
The five regions of putative selection are represented by the straight lines and include contiguous windows that passed both thresholds for elevated
divergence and low diversity (Right). These regions, across cat autosomes A1, B3, and D3, contain 12 known genes.
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GENETICS

GRIA2 and NPFFR2,haveelevatedd
N
/d
S
rates within the domestic
cat branch of the felid tree (Fig. 1). A third region on chromosome
D3 (Fig. 3) encompasses a single gene, DCC, encoding the netrin
receptor. This gene shows abundant expression in dopaminergic
neurons, and behavioral studies of DCC-deficient mice show altered
dopaminergic system organization, culminating in impaired memory,
behavior, and reward responses (46, 47). Two additional regions on
chromosome B3 harbor strong signatures of selection (Fig. S7). The
first contains three genes, including ARID3B (AT rich interactive
domain 3B), which plays a critical role in neural crest cell survival
(48). The second region contains a single gene, PLEKHH1,which
encodes a plekstrin homology domain expressed predominantly in
human brain. Human genome-wide association studies link variants
in PLEKHH1 with sphingolipid concentrations that, when altered,
lead to neurological and psychiatric disease (49).
The genetic signals from this analysis fall in line with the pre-
dictions of the domestication syndrome hypothesis (50), which
posits that the morphological and physiological traits modified by
mammalian domestication are explained by direct and indirect
consequences of mild neural crest cell deficits during embryonic
development. ARID3B,DCC,PLEKHH1, and protocadherins are
all implicated in neural crest cell migration. ARID3B is induced in
developing mouse embryos during the differentiation of neural crest
cells to mature sympathetic ganglia cells (51). DCC directly interacts
with the Myosin Tail Homology 4 (MyTH4) domain of MYO10
(myosin X) (52), a gene critical for the migratory ability of neural
crest cells. In this way, DCC regulates the function of MYO10 to
stimulate the formation and elongation of axons and cranial
neural crest cells in developing mouse (53) and frog embryos (54).
Like MYO10,PLEKHH1 contains a MyTH4 domain and interacts
with the transcription factor MYC, a regulator of neural crest cells,
to activate transcription of growth-related genes (55). Taken to-
gether, we propose that changes in these neural crest-related genes
underlie the evolution of tameness during cat domestication, in
agreement with analyses of other domesticated genomes (56–58).
We also examined regions of high genetic differentiation between
domestic cats and wildcats and observed enrichment in several
Wiki and Kyoto Encyclopedia of Genes and Genomes (KEGG)
pathways (S2.5 in Dataset S2), including homologous recombination
and axon guidance. Divergence in regions harboring homologous
recombination genes (RAD51B,ZFYVE26,BRCA2) may con-
tribute to the high recombination rate reported for domestic cats
relative to other mammals (59). Previous studies have suggested that
domestication may select for an increase in recombination as
a mechanism to generate diversity (60). Specifically, selection for
a recombination driver allele may be favored when it is tightly
linked to two or more genes with alleles under selection (61). We
hypothesize that the close proximity (<350 kb) of two adjacent genes
that regulate homologous recombination (ZFYVE26 and RAD51B,
which directly interact with BRCA2), two visual genes (RDH11
and RDH12) related to retinol metabolism and dark adaptation
(62), and one of our candidate domestication genes, PLEKHH1
(S2.4 in Dataset S2), represents such a case of adaptive linkage.
Aesthetic qualities such as hair color, texture, and pattern
strongly differentiate wildcats from domesticated populations
and breeds; however, unlike other domesticated species, less
than 30–40 genetically distinct breeds exist (63). At the beginning
of the cat fancy ∼200 y ago, only five different cat “breeds”were
recognized, with each being akin to geographical isolates (64).
Long hair and the Siamese coloration of “points”were the only
diagnostic breed characteristics. Although most breeds were
developed recently, following different breeding strategies and
selection pressures, much of the color variation in cats developed
during domestication, before breed development, and thus is
known as “natural”or “ancient”mutations by cat fanciers.
White-spotting phenotypes are a hallmark of domestication, and
in cats can range from a complete lack of pigmentation (white) to
intermediate bicolor spotting phenotypes (spotting) to white at only
the extremities (gloving). For instance, the Birman breed is char-
acterized by point coloration, long hair, and gloving (Fig. 4). A
recent study in several white-spotted cats localized the mutation
responsible for the spotting pigmentation phenotype within KIT
intron 1 (65). The KIT gene, located on cat chromosome B1 (66), is
primarily involved in melanocyte migration, proliferation, and sur-
vival (67). Surprisingly, direct PCR and sequencing excluded the
published dominant allele as being associated with the white col-
oration pattern in Birman (SI Materials and Methods). At the same
time, whole-genome resequencing data from a pooled sample of
Birman cats (n=4; SI Materials and Methods and S2.6 in Dataset
S2) identified the genomic region containing KIT as an outlier
exhibiting unusually low genetic diversity (Fig. 4). We therefore
resequenced KIT exons in a large cohort of domestic cats with
various white-spotting phenotypes to genotype candidate SNVs
(409 from 21 breeds, 5 Birman outcrosses, and 315 random bred
cats). We identified just two adjacent missense mutations that were
concordant with the gloving pattern in Birman cats (Fig. 4 and S2.7
in Dataset S2). Genotyping these SNPs in a larger sample including
150 Birman cats and 729 additional cats confirmed that all Birman
cats were homozygous for both SNPs and that all first-generation
outcrossed Birman cats with no gloving were carriers of the poly-
morphisms (S2.8 in Dataset S2).
Several lines of evidence indicate that the gloving phenotype
in the Birman breed is the result of these two recessive mutations
in KIT. Both mutations affect the fourth Ig domain of KIT,and
mutations in this motif near the dimerization site have been shown to
result in accelerated ligand dissociation and reduced downstream
signal transduction events (68). Interestingly, the frequency of the
Birman gloving haplotype in the Ragdoll breed, which shares an ex-
tremely similar white-spotting phenotype, was only 12.3%. We sug-
gest that other genetic variants, including the endogenous retrovirus
insertion in KIT intron 1 (65), likely contribute to the white-spotting
phenotype in the Ragdoll breed. The frequency of the Birman gloving
haplotype is just 10% in the random nonbreed population, thus il-
lustrating a case where segregating genetic variation in ancestral
nonbred populations has reached fixation within Birman cats through
strong artificial selection in a remarkably short time frame.
In conclusion, our analyses have identified genetic signatures
within feline genomes that match their unique biology and sensory
skills. The number of genomic regions with strong signals of selec-
tion since cat domestication appears modest compared with those in
Fig. 3. Comparison between domestic cats and wildcats identifying genes
within putative regions of selection in the domestic cat genome that are
associated with pathways related to synaptic circuitry and contextual clues
related to reward. We identified 130 regions along cat autosomes with ei-
ther pooled domestic Z(H
p
)<−4orZ(F
ST
)>4, and 5 annotated regions met
both criteria. A total of 12 genes was found within these regions, many of
which are implicated in neural processes; for instance, genes within regions
along chromosomes A1 and D3 are highlighted.
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the domestic dog (41), which is concordant with a more recent
domestication history, the absence of strong selection for specific
physical characteristics, as well as limited isolation from wild pop-
ulations. Our results suggest that selection for docility, as a result of
becoming accustomed to humans for food rewards, was most likely
the major force that altered the first domesticated cat genomes.
Materials and Methods
A female Abyssinian cat, named Cinnamon, served as the DNA source for all
sequencing reads (12). From this source we generated ∼14×whole-genome
shotgun coverage with Sanger and 454 technology. A BAC library was also
constructed and all BACs were end-sequenced. We assembled the combined
sequences using CABOG software (69) (SI Materials and Methods).
We estimated nonsynonymous and synonymous substitution rates using
the software PAML 4.0 (17). The following pipeline was used to perform
genome-wide selection analyses. (i) We identified 10,317 sets of 1:1:1:1:1
orthologs from the whole-genome annotations of human (GRCh37), cow
(UMD3.1), dog (CanFam3.1), tiger (tigergenome.org), and domestic cat using
the Ensembl pipeline (70). We tested for signatures of natural selection as-
suming the species tree topology (((cat, tiger), dog), cow, human). (ii )We
aligned the translated amino acid sequence of the coding region of each
gene using MAFFT (71) with the slow and most accurate parameter settings.
A locally developed Perl script pipeline was applied that removed poorly
aligned or incorrectly annotated amino acid residues caused by obvious
gene annotation errors within the domestic cat and tiger genome assem-
blies. Aligned amino acid sequences were used for guiding nucleotide-
coding sequences by adding insertion gaps and removing poorly aligned
regions. (iii) Model testing and likelihood ratio tests (LRTs) were performed
using PAML 4.0. Paired models representing different hypotheses consisted
of branch tests and branch-site tests (fixed ω=1 vs. variable ω). For the
branch-specific tests, free ratio vs. one-ratio tests were used to identify pu-
tatively positively selected genes. These genes were subsequently tested by
two-ratio and one-ratio models to identify genes with significant positive
selection of one branch versus all other branches (two-branch test). Signifi-
cance of LRT results used a threshold of P<0.05. We also report the mean
synonymous rates along the ancestral felid lineage as well as the tiger, cat,
and dog lineages (Fig. S1). We assessed enrichment of gene functional
clusters under positive natural selection using WebGestalt (72) (S1.5–S1.7 in
Dataset S1). Entrez Gene IDs were input as gene symbols, with the organism
of interest set to Homo sapiens using the genome as the reference set.
Significant Gene Ontology categories (73), Pathway Commons categories
(74), WikiPathways (75), and KEGG Pathways (76) were reported using
a hypergeometric test, and the significance level was set at 0.05. We
implemented the Benjamini and Hochberg multiple test adjustment (77) to
control for false discovery.
Using the whole-genome assembly of domestic cat (FelCat5) as a reference,
we mapped Illumina raw sequences from a pool of four wildcat individuals
[two European wildcats (F. s. silvestris) and two Eastern wildcats (F. s. lybica)]. Six
additional domestic cat breeds from different worldwide regional populations
were sequenced using the Illumina platform (SI Materials and Methods). Before
sequencing, we pooled samples by breed for the following individuals: Maine
Coon (n=5), Norwegian Forest (n=4), Birman (n=4), Japanese Bobtail (n=4),
and Turkish Van (n=4). Whole-genome sequencing was also performed on an
Egyptian Mau cat (n=1) and on the Abyssinian reference individual (n=1).
We combined the raw reads from the following breed sequencing experi-
ments (described above) before alignment and variant calling: Egyptian Mau,
Maine Coon, NorwegianForest, Birman,Japanese Bobtail,and Turkish Van. The
domestic cat pool (n=22) was sequenced to a genome coverage depth of ∼58-
fold, whereas the wildcat pool was sequenced to a depth of ∼7-fold (S2.1 in
Dataset S2). Base position differences were called using the convergent out-
comes of the software SAMtools (78) and VarScan 2 (79). Parameters included
aPvalue of 0.1 , a map quality of 10, and paramete rs for filtering by fal se
positives. A clustered variant filter was implemented to allow for a maximum
of five variant sites in any 500-bp window. Variants were finally filtered using
PoPoolation2 (80) to yield a high-confidence set of SNVs (n=6,534,957; fil-
tering steps included a minimum coverage of 8, a minimum variant count of 6,
a maximum coverage of 500 for the domestic cat pool, and a maximum cov-
erage of 200 for the wildcat pool).
We screened for positively selected candidate genes during cat domesti-
cation by parsing specific 100-kb windows that showed low diversity [low
pooled heterozygosity (H
p
)] in domestic cat breeds and had high divergence [a
high fixation index (F
ST
)] between domestic cats and wildcats (41, 81). F
ST
was
calculated using PoPoolation2, and measurements of H
p
were calculated using
a custom script. A total of 6,534,957 high-quality SNV sites were used to cal-
culate F
ST
and H
p
at each 100-kb window, and a step size of 50 kb was in-
corporated. All windows containing less than 10 variant sites were removed
from the analysis, resulting in n=46,906 100-kb windows along cat auto-
somes, as represented in the FelCat5 assembly. We Z-transformed the auto-
somal H
p
[Z(H
p
)] and F
ST
[Z(F
ST
)] distributions and designated as putatively
selected regions those that fell at least 4 SDs away from the mean [Z(H
p
)<−4
and Z(F
ST
)>4]. We applied a threshold of Z(H
p
)≤−4andZ(F
ST
)≥4forputative
selective sweeps, because windows below or above these thresholds represent
the extreme lower and extreme upper endsof the respective distributions (Fig.
S4). Windows with elevated F
ST
or depressed H
p
were annotated for gene
content using the intersect tool in BEDTools (82). Enrichment analysis of un-
derlying gene content was carried out using WebGestalt (72) using the same
methods as described above, except only significant WikiPathways (75) and
KEGG Pathways (76) were reported (S2.5 and S2.10–S2 .11 in Dataset S2).
Primers to amplify KIT exons (ENSFCAG00000003112) were designed using
Primer3Plus (83) and annealed to intronic regions flanking each exon. A PCR
assay was performed to determine the presence or absence of the dominant,
white-spotting retroviral insertion in KIT (65). An allele-specific PCR assay
was designed for genotyping exon 6 SNPs (S2.9 in Dataset S2). See SI Materials
and Methods for additional details.
ACKNOWLEDGMENTS. We thank The Genome Institute membersKim Kyung,
Dave Larson, Karyn Meltz Steinburg, and Chad Tomlinson for providing
assistance and advice on data analysis, and Tom Nicholas for manuscript
review. We also thank NIH/National Institute on Alcohol Abuse and Alcoholism
members David Goldman and Qiaoping Yuan. The cat genome and tran-
scriptome sequencing was funded by NIH/National Human Genome Research
Institute Grant U54HG003079 (to R.K.W.). Further research support included
grants to M.W.H. (National Science Foundation Grant DBI-0845494), W.J.M.
(Morris Animal Foundation Grants D06FE-063 and D12FE-019), T.M.-B. (European
Research Council Starting Grant 260372 and Spanish Government Grant
BFU2011-28549), and L.A.L. [National Center for Research Resources (R24
RR016094), Office of Research Infrastructure Programs/Office of the Director
(R24 OD010928), and Winn Feline Foundation (W10-014, W09-009)].
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www.pnas.org/cgi/doi/10.1073/pnas.1410083111 Montague et al.

Supporting Information
Montague et al. 10.1073/pnas.1410083111
SI Materials and Methods
Genome Assembly. The current draft assembly is referred to as
FelCat5 or Felis catus 6.2. There are ∼2.35 Gb (including Ns
in gaps) on ordered/oriented chromosomes, ∼15.4 Mb on the
chr*_random, and ∼11.74 Mb on chromosome Un. Initially, we
ran CABOG 6.1 (1) with default parameters (2). To evaluate
changes in contiguity, we altered a small set of the default pa-
rameters to obtain the best assembly possible. CABOG settings,
including parameters used, are available upon request.
To create an initial chromosomal version of the assembly, we
aligned marker sequences associated with a radiation hybrid (RH)
map (3) to the assembled genome sequence. The chromosomal
index file (.agp) contains the ordered/oriented bases for each
chromosome (named after the respective linkage group).
Once scaffolds were ordered and oriented along the cat
chromosomes using the RH map marker content (3), the as-
sembled cat genome was broken into 1-kb segments and aligned
against the dog genome (CanFam2) and human genome (hg19)
using BLASTZ (4) to align and score nonrepetitive cat regions
against repeat-masked dog and human sequences, respectively.
BLASTZ (4) and BLAT (5) alignments with the dog and human
genomes were then used to refine the order and orientation
information as well as to insert additional scaffolds into the
conditional scaffold framework provided by the marker assign-
ments. Alignment chains differentiated all orthologous and
paralogous alignments, and breakpoint identification confirmed
a false join within the genome assembly. Only “reciprocal best”
alignments were retained in the alignment set. Finally, satellite
sequences were identified in the genome, and centromeres were
placed along each chromosome using localization data (3) in
combination with the localization of the satellite sequences. In
the last step, finished cat BACs (n=86; totaling ∼14.92 Mb)
were integrated into the assembly, using the BLAT (5) aligner
for accurate coordinates.
Gene Family Expansions and Contractions. To explore gene family
expansions and contractions, we obtained peptides from cat, dog,
ferret, panda, cow, pig, horse, human, and elephant from Ensembl
(6). We clustered these into protein families by performing an
all-against-all BLAST (7) search using the OrthoMCL clustering
program (8). The clusters were converted to CAFE (9) format,
and families were filtered out based on the following groupings:
(i) at least one protein must be present in (elephant, human,
horse), and (ii) at least one protein must be present in (cat, dog,
ferret, panda, cow, pig), or the family is filtered out. We used
www.timetree.org to obtain divergence times for all species to
construct the following tree: (elephant:101.7, (human:94.2,
(horse:82.4, ((pig:63.1, cow:63.1):14.3, (cat:55.1, (dog:42.6, (ferret:38,
panda:38):4.6):12.5):22.3):5):11.8):7.5).
From phylogenetic inference, we found 50 expanded gene
families in the cat genome, of which 28 have known homologs in
other mammals (Fig. S3 and S1.8 in Dataset S1). Analyses using
CAFE 3.0 (9) confirmed contraction in multiple Or gene families
and expansion in the V1r gene family in the ancestor of modern
felids (S1.8 in Dataset S1), with differential gene gain and loss
within the cat family (Fig. S2).
In addition to the chemosensory Or and V1r gene families
mentioned, we found evidence for expansion of genes related
to processes of mechanotransduction (10) (PIEZO2), T-cell re-
ceptors (TRAV8), melanocyte development (11) (SOX10), and
meiotic processes (SYCP1). Four gene families were complete
losses along the cat lineage; the annotations for these entries for
other species include gene families related to reproduction
(spermatogenesis-associated protein 31D1 and precursor acro-
somal vesicle 1), secretory proteins (precursor lipophilin), and
hair fibers (high sulfur keratin associated).
Segmental Duplication, Copy Number (CNV) Discovery, and Structural
Variation.
Sequencing data. For the domestic cat (Abyssinian), sequenced with
Illumina technology, bam files resulting from mapping 100-bp
reads were used to recover the original fastq reads, which were
clipped into 36-bp reads after trimming the first 10 bp to avoid
lower-quality positions. That is, we used a total of 1,485,609,004
reads for mapping (coverage 21.8×).
Reference assembly. We downloaded the FelCat5 assembly from the
UCSC Genome Browser (12). The 5,480 scaffolds either un-
placed or labeled as random were concatenated into a single
artificial chromosome. In addition to the repeats already masked
in FelCat5 with RepeatMasker (www.repeatmasker.org) and
Tandem repeats finder (13), we sought to identify and mask
potential hidden repeats in the assembly. To do so, chromo-
somes were partitioned into 36-bp K-mers (with adjacent K-mers
overlapping 5 bp), and these were mapped against FelCat5 using
mrsFAST (14). Next, we masked positions in the assembly
mapped by K-mers with more than 20 placements in the genome,
resulting in 5,942,755 bp additionally masked compared with the
original masked assembly (Fig. S3).
Mapping and copy number estimation from read depth. In the domestic
cat, the 36-bp reads resulting from clipping the original fastq reads
(see above) were mapped to the prepared reference assembly
using mrFAST (15). mrCaNaVaR (version 0.41) (15) was used to
estimate the copy number along the genome from the mapping
read depth. Briefly, mean read depth per base pair is calculated
in 1-kbp nonoverlapping windows of nonmasked sequence (that
is, the size of a window will include any repeat or gap, and thus the
real window size may be larger than 1 kbp). Importantly, because
reads will not map to positions covering regions masked in the
reference assembly, read depth will be lower at the edges of these
regions, which could underestimate the copy number in the sub-
sequent step. To avoid this, the 36 bp flanking any masked region
or gap were masked as well and thus are not included within the
defined windows. In addition, gaps >10 kbp were not included
within the defined windows. A read depth distribution was ob-
tained through iteratively excluding windows with extreme read
depth values relative to the normal distribution, and the remaining
windows were defined as control regions (Fig. S3 and S1.9 in
Dataset S1). The mean read depth in these control regions was
considered to correspond to a copy number equal to two and was
used to convert the read depth value in each window into a GC-
corrected absolute copy number. Note that the control/noncontrol
status was determined based on the read depth distribution,
making this step critical for further copy number calls. Of the
993,102 control windows, none aligned to the artificial chromo-
some (see above), and 37,123 (3.7%) were on chromosome X in
the sample.
Calling of duplications and deletions. The copy number distribution in
the control regions was used to define specific gain/loss cutoffs as
the mean copy number plus/minus three units of SD (calculated
not considering those windows exceeding the 1% highest copy
number value). Note that because the mean copy number in the
control regions was equal to two (by definition), the gain/loss
cutoffs were largely influenced by the SD.
Montague et al. www.pnas.org/cgi/content/short/1410083111 1of12

We used two methods to call duplications: M1, the circular
binary segmentation (CBS) method (16), was used to combine
1-kbp windows that represent segments with significantly the same
copy number. Segments with copy number (defined as the me-
dian copy number of the 1-kbp windows comprising the segment)
exceeding the gain/loss cutoffs defined above (but lower than 100
copies in the case of duplications) were merged and called as
duplications or deletions if comprising more than 10 1-kbp
windows (∼10 kbp); finally, only duplications with >85% of their
size not overlapping with repeats were retained for the analyses.
As a second method (M2), we also called duplications avoiding
the segmentation step with the CBS method by merging 1-kbp
windows with copy number larger than sample-specific gain cutoff
(but lower than 100 copies) and then selecting those regions
comprising at least five 1-kbp windows and >10 kbp; similarly,
only duplications with >85% of their size not overlapping with
repeats were retained for the analyses.
In M1, the copy number distribution in the control regions was
used to define sample-specific gain/loss cutoffs as the mean copy
number plus/minus three units of SD (calculated not considering
those windows exceeding the 1% highest copy number value).
Note that because the mean copy number in the control regions is
equal to two by definition, the gain/loss cutoffs will be largely
influenced by the SD. Then, we merged 1-kbp windows with copy
number larger than sample-specific gain cutoff (but lower than
100 copies) and identified as duplications the regions that
comprised at least five 1-kbp windows and >10 kbp. Finally, only
duplications with >85% of their size not overlapping with re-
peats were retained. This method is highly restrictive (conser-
vative), so we used an alternative method (M2) similar to what
had been previously done with Sanger capillary reads (17). We
performed a 5-kbp sliding window approach and required six out
of seven windows with a significantly higher read depth, relative
to the control regions, to consider a region as duplicated.
Several categories were significantly overrepresented in regions
of expanded CNV (Fig. S3 and S1.10–S1.12 in Dataset S1), some
of which overlap those identified in other CNV studies for other
taxa (18–22). In the cat, we note that an expanded CNV region
on chromosome B2 contained a pair of genes that transcribe an
MHC class I antigen and an MHC class I antigen precursor. The
MHC class I molecules present self-antigens to cytotoxic CD8
+
T lymphocytes and regulate natural killer cell activity. Inves-
tigations of MHC genes in other domesticated animals, including
pig (23), sheep (24), and cow (25, 26), have shown that MHCs in
these groups are affected by CNV. These results suggest that
CNV is an additional common source of disease resistance or
susceptibility variability in the MHC of the cat as well.
V1r/Or Identification and Annotation. Published V1r and Or se-
quences from human, mouse, rat, cow, dog, and opossum were
used as the query sequences for BLAST (7) searches against the
domestic cat genome. All query sequences were previously
shown as belonging to V1r (27, 28) and Or (29) subfamilies, thus
ensuring identification of the most complete gene repertoires.
We enforced an E-value threshold of 10
−5
for filtering BLAST
results. All identified sequences were extended 1.5 kb on either
side for open reading identification and assessment of func-
tionality. If multiple start codons were found, the alignment re-
sults of known intact mammalian V1r and Or amino acid
sequences were used as guidance for determining the most ap-
propriate one. Any putative genes containing early stop codons,
frameshift mutations, and/or incomplete gene structure (i.e., not
containing three extracellular regions, seven transmembrane
regions, and three intracellular regions) were designated as
pseudogenes. To confirm orthology, we aligned all members of
the V1r and Or gene families and constructed maximum likeli-
hood trees rooted with appropriate outgroup taxa, such as V2r
and taste receptor gene families. Assembled whole-sequencing
data were obtained from the Ensembl database (6) [domestic cat:
vFelCat5; domestic dog: vCanFam; domestic horse: vEquCab2; hu-
man: vGRCh39; domestic cow: vBosTau7; great panda: vAilMel1;
and tiger (tigergenome.org)]. V1r gene clusters were defined as
all identified functional genes and pseudogenes within a 2-Mb
window. Synteny blocks of different mammals were identified
using the software SyntenyTracker (30).
Felid V1r sequencing. The following felid taxa were used for
V1r PCR and sequencing: Felis catus (domestic cat; FCA), Felis
nigripes (Black-footed cat; FNI), Prionailurus bengalensis (Leo-
pard cat; PBE), Prionailurus viverrinus (Fishing cat; PVI), Puma
concolor (Cougar; PCO), Puma yagouaroundi (Jaguarundi; PYA),
Acinonyx jubatus (Cheetah; AJU), Lynx canadensis (Canadian
Lynx; LCA), Lynx lynx (Eurasian Lynx; LLY), Lynx pardinus
(Iberian Lynx; LPA), Lynx rufus (Bobcat; LRU), Leopardus pardalis
(Ocelot; LPA), Leopardus wiedii (Margay; LWI), Leopardus geof-
froyi (Geoffroy’scat;LGE),Leopardus colocolo (Pampas cat;
LCO), Leopardus tigrinus (Tiger cat; LTI), Profelis serval (Ser-
val; PSE), Profelis caracal (Caracal; PCL), Pardofelis temminckii
(Asian Golden cat; PTE), Pardofelis marmorata (Marbled cat;
PMA), Neofelis nebulosa (Clouded Leopard; NNE), Panthera leo
(Lion; PLE), Panthera onca (Jaguar; PON), Panthera pardus
(Leopard; PPA), Panthera tigris (Tiger; PTI), and Panthera uncia
(Snow Leopard; PUN). Forty-three pairs of primers for V1r
amplification were designed using several versions of the domestic
cat whole-genome assembly (FelCat1–FelCat5). Target amplicons
were designed to be longer than 1.1 kb to ensure amplification of
the complete coding region sequence. PCR was performed using
PlatinumTaq DNA polymerase using a touchdown profile of 60–55
°C, as described (31). All amplicons were sequenced using Sanger
sequencing on an ABI 3700 (Applied Biosystems). A total of 1,055
sequences of intact V1r genes and pseudogenes from 27 cat species
were submitted to GenBank under accession numbers KJ923925–
KJ924979.
Sequence alignment and phylogenetic reconstruction. We aligned our
previously unidentified V1r sequences with known published V1r
sequences using MAFFT (32) with stringent parameter settings.
Coding sequences were aligned under the guidance of the
translated amino acid alignment results. Poorly aligned 5′and 3′
flanking regions were trimmed before tree building. MODELTEST
(33) was used to estimate the best nucleotide substitution models
and parameters for sequence data. Maximum likelihood trees (with
500 bootstrap replicates) were constructed with RAxML7.0.0 (34).
Estimation of gene gain and loss within V1r and Or gene families. We
compared the Or and V1r gene trees generated above with a
mammalian species tree (35) to estimate gene gain and loss using
the software NOTUNG (36). We examined variation in V1r and
Or gene family repertoire size among different domestic cat breeds
by aligning Illumina reads to the cat assembly using BWA (37).
Mapping results were analyzed with CNVnator (38). We reesti-
mated the tiger Or and V1r repertoires by remapping all of the raw
tiger Illumina reads to the Siberian tiger assembly (tigergenome.
org) as well as the current domestic cat version 6.2 assembly.
Natural Selection Tests.
Phylogenetic analyses by maximum likelihood. Four sets of models were
applied for null hypothesis and alternative hypothesis compar-
isons. Set 1 involved a comparison between the free-ratio model
and the one-ratio model, whereas set 2 compared the two-ratio
model with the one-ratio model. These two comparisons are
classified as branch-specific tests, which were used to identify
accelerated rates of genes on specific branches of an evolution-
ary tree. In addition, we performed site-specific tests, which
detected natural selection acting on specific amino acid sites of
the protein. For this step, we performed model tests within sets
3 and 4, which involved model 1a (nearly neutral) versus model
2a (positive selection) and model 7 (gamma) versus model 8
Montague et al. www.pnas.org/cgi/content/short/1410083111 2of12

(gamma and ω) to evaluate and identify specific amino acid sites
that were potentially under positive selection.
To evaluate the structural influence of domestic cat non-
synonymous substitutions from the common ancestor of felids, we
used TreeSAAP (39) to measure 31 structural and biochemical
amino acid properties while applying the tree topology (human,
(cow, (dog, (cat, tiger)))). We used a significance threshold of P<
0.001 to report structural or biochemical properties of amino acid
substitutions likely to affect protein function. We also used
PROVEAN (40) to predict the potential functional impact of
domestic cat-specific amino acid substitutions and indels. We
considered amino acid substitutions as “deleterious”if the
PROVEAN score was ≤−2.5. We considered amino acid substitu-
tions as “neutral replacements”if the PROVEAN score was >−2.5
(Fig. S1).
To explore the heterogeneous selection pressure across posi-
tively selected genes, peaks of high d
N
/d
S
were visualized using
sliding window analyses performed across alignments of the full
coding sequence. Sliding windows of ωvalues were estimated
using the Nei and Gojobori method (41) with a default window
size of 90 bp and a step size of 18 bp.
Many positively selected genes appear to have played a role in
the sensory evolution of felines, as highlighted above. For in-
stance, chemosensory genes with significant signatures of positive
selection in the Felinae include two gustducin-coupled bitter taste
receptors, TAS2R1 and TAS2R3, as well as a cofactor, RTP3
(S1.3 in Dataset S1). We speculate that selection at these loci
increased sensitivity to and avoidance of toxic prey items in the
hypercarnivorous ancestor of cats (42). Other positively selected
genes appear to have played a role in the morphological evolu-
tion of carnivores. For instance, all carnivores have robust claws
(except where they are secondarily lost) that serve as critical
adaptations to capture and disarticulate prey. The RSPO4 gene
(S1.1 in Dataset S1) plays a crucial role in nail morphogenesis
across mammals, and its expression is restricted to the de-
veloping nail mesenchyme (43). Further, the recessive human
disorders anonychia/hyponychia congenita result from mutations
in RPSO4 (44), and are characterized by absence of or severe
reduction in fingernails and toenails. Evidence of positive se-
lection within the RSPO4 gene in the ancestral carnivore lineage
likely reflects molecular adaptations driving enhanced nail
morphology.
Genome mapping and variant analysis. We next performed whole-
genome analyses of cats from different domestic breeds [Maine
Coon (SRX026946, SRX026943, SRX026929), Norwegian Forest
(SRX027004, SRX026944, SRX026941, SRX026909, SRX026901),
Birman (SRX026955, SRX026947, SRX026911, SRX026910),
Japanese Bobtail (SRX026948, SRX026928, SRX026912), Turkish
Van (SRX026942, SRX026930, SRX026913), and Egyptian Mau
(SRX019549, SRX019524, SRX026956, SRX026945)] and wild-
cats [i.e., other F. silvestris subspecies (SRX026960)] using pooling
methods that control for genetic drift (45). All reads were pre-
processed by removing duplicate reads and only properly paired
reads were aligned to the FelCat5 reference using BWA (37) (n=
2,332,398,473 reads from the pooled domestic cats combined; n=
189,543,907 reads from pooled wildcats). A total of 8,676,486 and
5,190,430 high-quality single-nucleotide variants (SNVs) among
domestic breeds and wildcats, respectively, at a total of 10,975,197
sites, passed the thresholds using our initial variant-calling meth-
ods with SAMtools (46) and VarScan (47). Because SNVs for the
domestic and wildcat pools were called separately, variants as-
certained in one may not be present in the other. This can be due
to homozygosity for the reference allele or inadequate data at the
locus. We therefore implemented a consensus-calling analysis for
the combined variant set to categorize each SNV as high-quality
passing, low-quality failure, or no sequence coverage within each
pool for all 10,975,197 passing sites. To do this, we generated
a two-sample mpileup using SAMtools (46) for every site that was
called a variant. We next implemented the mpileup2cns command
in VarScan (47) with the minimum read depth set to three. Be-
cause every site in the mpileup passed the initial false positive
filtering in at least one pool, we were able to determine the per-
centage of variant overlap between the pool of domestic cats and the
pool of wildcats. This revealed 9,010,197 shared variant alleles be-
tween the domestic cats and wildcats, indicating that 1.7% and
10.3% of sites with variant alleles were unique to domestic cats and
wildcats, respectively (Fig. S4). As expected, due to the coverage
differences between the pools, a total of 3,121 and 745,091 sites, in
the pooled domestic cats and pooled wildcats, respectively, contained
lowcoverage(fewerthanthreealignedreads)ormissingcoverage.
We next used VCFtools (48) to explore the extent of overlap
between the different variant callers. For the domestic cat pool,
SAMtools (46) called 11,119,091 variants and VarScan (47) called
10,138,788 variants. A total of 9,683,549 variants overlapped, re-
vealing that 4.5% and 12.9% of the original VarScan (47) and
original SAMtools (46) calls, respectively, were undetected by the
other variant caller. For the wildcat pool, SAMtools (46) called
9,860,972 variants and VarScan (47) called 9,098,242 variants. A
total of 7,848,268 variants overlapped, revealing that 13.7% and
20.4% of the original VarScan (47) and original SAMtools (46)
calls, respectively, were undetected by the other variant caller.
SNV validation. We verified our high-quality set of SNVs by com-
paring the list of markers with those of an SNP array developed
previously (49). To accomplish this, we used BLAST (7) to locate
the best-hit coordinates along the F. catus 6.2 reference assembly
for each of the array variants. We then parsed our pooled domestic
cat variant file for matching coordinates and discovered 184 out of
384 variants (47.9%). The calls made by our pipeline matched the
variant on the chip in 183 out 184 cases (99.5%).
Breed differentiation. We verified the genetic relationships among
the breeds using multidimensional scaling (MDS) and a pop-
ulation stratification analysis. Seven populations of 26 domestic
cats were analyzed, including the breeds described above as well as
a population of Eastern Random Bred cats (n=4; SRX026993).
Genome mapping and variant calling was performed on a per-breed
basis using described variant-calling methods (above). After aligning
the short reads to FelCat5, we identified 77,749 high-quality var-
iants that were shared among all seven breeds. The pedigree ge-
notype file was quality-controlled with PLINK (50) to remove all
individuals with more than 80% missing genotype data, all SNVs
missing in more than 5% of cases, and all SNVs with less than 5%
minor allele frequency (MAF). Following quality control filtering,
a total of 44,377 autosomal SNVs remained. MDS was imple-
mented using PLINK (50) to produce an output file with identity
by state values, and genetic distances of the first four principal co-
ordinates were visualized (Fig. S5). Model-based clustering was
performed with ADMIXTURE (51). A total of 20 replicates of
K=2toK=20 was run in unsupervised mode, each with random
seeds and fivefold cross-validation. The replicates of each Q file for
each K were merged using the LargeKGreedy method (with random
input orders) using the program CLUMPP (52). The merged Q files
were then visualized in DISTRUCT (53) to output plots of esti-
mated membership coefficients for each individual according to
each K, with K =5 offering the highest support (Fig. S5).
Discovering putative regions of selection in the domestic cat genome. As
a quality control assessment, the average H
p
and F
ST
of all au-
tosomal 100-kb windows were plotted against the corresponding
number of segregating sites per window. In line with our ex-
pectations, H
p
was positively correlated with the number of
segregating sites (rho =0.021, P<0.001, Spearman; Fig. S5)
whereas F
ST
was negatively correlated (rho =0.225, P<0.001,
Spearman; Fig. S5), suggesting that the number of variants per
window was lower in our putative regions of selection due to the
loss of linked variation following an adaptive sweep. We also
compared the depth of coverage at variant sites within the
putative regions of selection with the depth of coverage at variants
Montague et al. www.pnas.org/cgi/content/short/1410083111 3of12

found within all other genomic regions. The average read depth
among the 3,265 variant positions for pooled domestic cats within
the five regions of putative selection was relatively equivalent to
the average read depth of all 8,676,486 variants across all auto-
somes for pooled domestic cats (53.82 versus 53.65, respectively).
Although accurate detection of heterozygosity is dependent on
coverage, similar depths among the breed pools and members of
each pool were not obtained for this study. Further, individual
cats were not indexed when pooling by breed. Although equal
numbers of samples among pools and subsets were difficult to
obtain, we tested whether unequal representation between do-
mestic cat and wildcat contributed to variance of the divergence
statistics across the genome by reperforming the F
ST
analysis
based on a random subsample of the domestic cat data where the
average coverage (6.81×) approximated the original coverage for
the wildcat pool (6.84×), with ∼1.1×coverage contributed by
each domestic breed pool. First, the variant-calling pipeline
identified 3,494,488 total variants in the subsampled data. A final
variant set consisting of 1,274,175 autosomal variants was then
used for a sliding window analysis of F
ST
using the same methods
as the original analysis. When analyzing the subsampled data, all
windows that passed the threshold under the original analysis
were found within the 99th percentile of highest F
ST
using the
subsampled domestic cat data (Fig. S5). All of the original
windows were thus identified as windows with high divergence
using the subsampled data. These results suggest that the un-
equal sample sizes of domestic cats and wildcats likely had little
effect on the overall results of our sliding window analyses.
Analysis of the X chromosome. To not confound the results of the
autosomal analyses, we analyzed the X chromosome separately,
using the method as described previously for the autosomes. We
found that the average pooled heterozygosity, H
p
,ishigher(H
p
X:
0.496 vs. H
p
A: 0.385) and the average fixation index, F
ST
,ishigher
(F
ST
X: 0.674 vs. F
ST
A: 0.429) on X compared with on autosomes.
We also note that the SDs of the H
p
(σX: 0.049 vs. σA: 0.029) and
F
ST
(σX: 0.183 vs. σA: 0.074) distributions are larger on the X
chromosome relative to the autosomes. No windows passed the
thresholds of significance [Z(H
p
)<−4orZ(F
ST
)>4] used for the
autosomal analyses. We instead applied a lower threshold of 1.5
SDs from the mean of both the H
p
and F
ST
distributions. A total of
54 windows, representing 36 unique regions, passed this cutoff in
the F
ST
analysis (S2.12 in Dataset S2). A total of 210 windows
representing 72 unique regions passed this threshold for the H
p
analysis (S2.13 in Dataset S2). Known genes underlying regions of
low domestic H
p
and high F
ST
(Fig. S6 and S2.14 in Dataset S2)
include cyclin B3 (CCNB3), Cdc42 guanine nucleotide exchange
factor 9 (ARHGEF9), zinc finger C4H2 domain containing (ZC4H2),
family with sequence similarity 155, member B (FAM155B), proto-
cadherin 19 (PCDH19), annexin A2 (ANXA2), and brain expressed
X-linked 5 (BEX5). Our sliding window analysis along the autosomes
revealed a strong trend associating genomic signatures of selection in
domestic cats with genes influencing memory, fear-conditioning be-
havior, and stimulus-reward learning, particularly those predicted to
underlie the evolution of tameness(54).ThisanalysisoftheX
chromosome reveals similar functional trends, with four of six regions
containing genes associated with neurological diseases and aberrant
synaptic activity, including an additional protocadherin locus.
The Z-transformation technique, outlined above, resulted in
a skewed (i.e., not normal) distribution (Fig. S6), so the con-
clusions must be viewed cautiously. By applying a percentile
approach, we found that no genes underlie windows that met
thresholds for either the 99th percentile or the 95th percentile for
both F
ST
and domestic H
p
. Only a single window met the 99th
percentile for F
ST
and the 99th percentile for domestic H
p
. This
window (X:23800000–23900000), although noncoding, is within
the X-linked MAGE gene family complex. The protocadherin
gene that we highlighted above (PCDH19) was found within the
95th percentile threshold for F
ST
and the 90th percentile for
domestic H
p
. The annexin gene (ANXA2), which is located
within an adjacent window to PCDH19, met the 95th percentile
threshold for F
ST
and the 85th percentile for domestic H
p
. Only
one other gene displayed a higher F
ST
value than PCDH19 and
ANXA2:BEX5, also highlighted by our Z-transformation anal-
ysis, met the 99th percentile threshold for F
ST
and the 90th
percentile for domestic H
p
.
Pigmentation Patterns in Domestic Cat Breeds. Several breeds rep-
resent random bred populations of cats that do not have strong
selection on a specific trait, such as Maine Coon and Norwegian
Forest; however, the vast majority of cat breeds, including Jap-
anese Bobtail, Birman, Egyptian Mau, and Turkish Van, likely
experienced strong selection on novel and specific mutations (i.e.,
morphological traits and pigmentation patterns), as individuals
were selected from random bred populations.
The genomic sequence data from the pooled Birman breed
revealed an ∼10-Mb homozygous block located directly up-
stream of KIT. The average nucleotide diversity for 100-kb
windows adjacent to KIT was lower (ChrB1: 161.5–161.9 Mb;
pi =0.0011) than the average nucleotide diversity for 100-kb win-
dows across all autosomes (pi =0.2185) or the average nucleo-
tide diversity for 100-kb windows across ChrB1 (pi =0.1762)
(Fig. 4). An additional analysis of 63K single-nucleotide variants
in individual Birman cats revealed an ∼5-Mb homozygous block
located directly upstream of KIT. This loss of variation could be
explained by genetic drift (e.g., inbreeding, the small founder
population of the breed) or as a consequence of selection (e.g.,
the white gloving trait is fixed and recessive). We hypothesized that
an extensive homozygous block is a measure of the selection on the
gloving trait because Birman is highly selected for coat color, and
we discovered a unique pair of fixed SNVs within the Birman breed
that are associated with amino acid changes in KIT.
Samples and genotyping. We noninvasively collected DNA samples
from all domestic cats by buccal swabs using a cytological brush or
cotton tip applicator. DNA was isolated using the QIAamp DNA
Mini Kit (Qiagen). The previous linkage analysis pedigree from the
Waltham Centre for Pet Nutrition (55) was extended from 114 to
147 cats to refine the linkage region. Phenotypes were determined
as in the previous study (55). Two previously published short tan-
dem repeats (STRs) (56) (FCA097 and FCA149) and four pre-
viously unidentified feline-derived STRs (UCDC259b,UCDC443,
UCDC487,andUCDC489) (S2.9 in Dataset S2), flanking KIT on
feline chromosome B1, were genotyped. Genotyping for the mark-
ers and two-point linkage between the microsatellite genotypes and
the spotting phenotype was conducted using the LINKAGE (57)
and FASTLINK (58) programs as in previous studies (59).
Genomic analysis of KIT. To identify KIT exons, publicly available (in
GenBank) sequences from various species were aligned, including
Homo sapiens (NM_000222.2), Canis familiaris (NM_001003181.1),
Mus musculus (NM_021099.3), and Equus caballus (NM_001163866.1)
and a partial sequence for the domestic cat, F. catus (NM_001009837.3),
because F. catus KIT was located on the previous version of the
assembly (60) (GeneScaffold_3098:168,162–233,592). Primers (Op-
eron) were tested for efficient product amplification, and the final
magnesium and temperature conditions for each primer pair are
presented in Dataset S2 (S2.9). PCR and thermocycling conditions
were conducted as previously described (61). The PCR products
with the appropriate lengths were purified using the ExoSap (USB)
enzyme per the manufacturer’s recommendations. Purified genomic
products were sequenced using BigDye Terminator Sequencing Kit
version 3.1 (Applied Biosystems), purified with Illustra Sephadex
G-50 (GE Healthcare) according to the manufacturer’srecom-
mendations, and electrophoretically separated on an ABI 3730
DNA Analyzer (Applied Biosystems). Sequences were verified and
aligned using the software Sequencher version 4.8 (Gene Codes).
The complete coding sequence for F. catus KIT was submitted to
GenBank under accession number GU270865.1.
Montague et al. www.pnas.org/cgi/content/short/1410083111 4of12

KIT mRNA analysis. RNA from a nonwhite control cat was isolated
from whole blood using the PAXgene Blood RNA Kit (Qiagen)
following the manufacturer’s directions. The 5′UTR amplifica-
tion and the PCR analysis were conducted as previously de-
scribed (62). The 5′RACE used the cDNA pool generated by
the KIT-specific primers (S2.9 in Dataset S2). The 5′RACE
PCR products were cloned using the TOPO TA Cloning Kit
(Invitrogen) before sequencing. Five 5′RACE cDNA clones
from the control cat were selected and sequenced. Genomic
primers (S2.9 in Dataset S2) were then designed in the 5′UTR
region to sequence the cats used for the genomic analysis of KIT
(S2.7 in Dataset S2).
KIT SNP genotyping. An allele-specific PCR (AS-PCR) assay was
designed for genotyping exon 6 SNPs (S2.9 in Dataset S2). Both
allele-specific primer pairs annealed at the 2-nt primer–template
mismatch (c.1035_1036delinsCA; p.Glu345Asp; His346Asn; S2.9
in Dataset S2). The AS-PCR assay used 1×buffer, 1.5 mM
MgCl
2
, 200 μM each dNTP, and 0.1 U Taq (Denville), per 15 μL
of reaction mixture. The primer concentrations in each PCR
were 0.67 μM KITgloA-FAM, 0.67 μM KITgloB-VIC, and 0.67
μM KITR. PCR conditions were: initial denaturation at 95 °C for
5 min, followed by 35 cycles of 95 °C for 30 s, 60 °C for 30 s, and
72 °C for 45 s, and a final extension step of 72 °C for 7 min. The
amplified products were separated on an ABI 3730 DNA Ana-
lyzer (Applied Biosystems). The genotypes were scored based on
fluorescence intensity using the software STRand (63). The
variants and exons within KIT were schematically presented with
FancyGene (64).
Exploring other potential regulatory variation within KIT. We initially
planned to investigate only the exonic regions of KIT, even
though flanking or intronic regions often regulate gene expres-
sion. Along this line of reasoning, an ∼7-kb retroviral (FERV1)
insertion within KIT intron 1 was recently identified as the
causative factor for white spotting among different cat breeds
(65); however, the Birman breed was not surveyed for the in-
sertion. We therefore searched for the dominant, white-spotting
FERV1 insertion sequence in the pooled Birman genomic se-
quence data (with estimated 4×coverage). To do this, we aligned
all ∼190 million 50-bp reads from the Birman pool to the 7,296-
bp FERV1 insertion sequence and generated a consensus to
compare with the FERV1 reference. A total of 778 reads aligned
using BWA (37), but the result was ambiguous due to the fol-
lowing observations: (i) 1,169 bp (16%) of the FERV1 reference
were missing across 23 regions, with an average of 50.8 bp
missing per region; and (ii) there were regions of 275, 173, and
296 bp within the FERV1 reference with no read coverage. In-
stead, we designed a long-range PCR experiment (for primers
and conditions, see ref. 65) to capture the white-spotting alleles
in mitted and bicolor Ragdoll (n=10), Birman (n=10), and
other white-spotted (n=5) and solid (n=5) cats. Whereas the
FERV1 insertion was confirmed in spotted Ragdolls and other
spotted cats, we found no evidence for the insertion in all Birman
cats and solid cats. These results demonstrate a second mecha-
nism for white spotting in the Birman breed while also confirming
a separate mode of inheritance. Future experiments will inves-
tigate how the fixed mutations in KIT exon 6 interact with KIT
regulatory elements during expression.
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Fig. S1. (A) Predicted structure of the domestic cat STARD5 gene. Positively selected amino acid sites are indicated with red arrowheads. (B) Results of the
d
N
/d
S
test suggest an accelerated evolutionary rate of the STARD5 gene on the domestic cat branch. Numbers on each branchare scores of the estimated d
N
/d
S
,d
N
,
and d
S
.(C) Average synonymous mutation rates along branches used for assessments of positive selection. Dashed lines indicate relationships since rates are not
reported for cow and human.
Montague et al. www.pnas.org/cgi/content/short/1410083111 6of12

Fig. S2. (A) Maximum likelihood phylogenetic tree of functional V1r genes and long pseudogenes from the domestic cat, giant panda, and dog genomes. (B)
Gene tree of the V1r supergene family determined for 35 feline species suggesting the early expansion of V1r genes in the common ancestor of felids. (C)
Distribution of the V1r gene family in the domestic cat genome. Intact genes are denoted in black; pseudogenes are denoted in red. (D) Detected V1r gene loss
among different lineages of the Felidae. Colored boxes in the tree indicate gene loss events based on 48 putatively intact V1r genes present in the common
ancestor of all current felids.
Montague et al. www.pnas.org/cgi/content/short/1410083111 7of12

Fig. S3. (A) Raw counts for the number of gene family expansions, number of genes gained, number of gene family contractions, and number of genes lost
among horse, panda, cow, human, elephant, cat, ferret, dog, and pig. (B) Significant results for the number of rapid gene family expansions and the number of
rapid gene family contractions among horse, panda, cow, human, elephant, cat, ferret, dog, and pig. (C) Cumulative distribution of additional masking
achieved by masking overrepresented K-mers in Fca 6.2 (FelCat5 in UCSC). (D) Distribution of 1-kbp copy number values in control and noncontrol regions. The
number of windows in each distribution is indicated. (E) CNV map of expansions on domestic cat autosomes.
Montague et al. www.pnas.org/cgi/content/short/1410083111 8of12

Fig. S4. (A) Analysis pipeline for determining putative regions of selection using variant data. (B) Summary results of variant calling for pooled domestic cats
(n=22) and pooled wildcats (n=4). (B1) Percentage of overlapping variant alleles at each of the sites where a high-quality variant was detected. (B2)Per-
centage of unique and overlapping variant sites included in the sliding window analysis comparing domestic cats with wildcats based on stringent filtering
parameters. Also included are transition:transversion ratios per pool as well as counts of variant types per pool. (C) Distribution of pooled heterozygosity, H
P
,
and average fixation index, F
ST
, and corresponding Z transformations, Z(H
P
) and Z(F
ST
), estimated in 100-kb windows across all cat autosomes. (D) Circos plot of
(i) pooled domestic cat versus pooled wildcat F
ST
,(ii) pooled domestic cat H
p
, and (iii) pooled wildcat H
p
results for each 100-kb window (with a step size of
50 kb) along each chromosome. Windows with elevated F
ST
or depressed H
p
are depicted as red dots, whereas all other windows are depicted as black dots.
Montague et al. www.pnas.org/cgi/content/short/1410083111 9of12

Fig. S5. (A) MDS plot depicting the relationship between individuals within the seven domestic cat pools used for the analysis of breed differentiation. (B)
Admixture results for K =5 showing genetic differentiation between eastern (Birman) and western (Maine Coon) populations, with moderate admixture
between other breeds, including eastern random bred (ERB) individuals. (C) The average H
P
and F
ST
of all autosomal 100-kb windows plotted against the
corresponding number of segregating sites per window. H
P
is positively correlated with the number of segregating sites, whereas F
ST
is negatively correlated.
(D) The F
ST
results for all autosomal 100-kb windows for the full coverage (∼55×) pooled domestic analysis (xaxis) are plotted against the F
ST
results for all
autosomal 100-kb windows for the subsampled (∼7×) pooled domestic analysis (yaxis).
Montague et al. www.pnas.org/cgi/content/short/1410083111 10 of 12

Fig. S6. (A) Z-transformed average fixation index (only positive values are shown), Z(F
ST
), and pooled heterozygosity (only negative values are shown), Z(H
p
),
in 100-kb windows across chromosome X. Red dots indicate windows with (i) high F
ST
and low H
p
along with (ii) underlying gene content. (B) Distribution of
pooled heterozygosity, H
p
, and average fixation index, F
ST
, and corresponding Z transformations, Z(H
p
) and Z(F
ST
), estimated in 100-kb windows across
chromosome X.
Montague et al. www.pnas.org/cgi/content/short/1410083111 11 of 12

Fig. S7. (A) Plots of (i) pooled domestic cat versus pooled wildcat F
ST
results (red), (ii) pooled domestic cat H
p
results (light blue), and (iii) pooled wildcat H
p
results (dark blue) for each 100-kb window (with a step size of 50 kb) along chromosome B3 with increasing resolution to the genes underlying region 3. (B)
Plots of (i) pooled domestic cat versus pooled wildcat F
ST
results (red), (ii) pooled domestic cat H
p
results (light blue), and (iii ) pooled wildcat H
p
results (dark
blue) for each 100-kb window (with a step size of 50 kb) along chromosome B3 with increasing resolution to the genes underlying region 4.
Other Supporting Information Files
Dataset S1 (PDF)
Dataset S2 (PDF)
Montague et al. www.pnas.org/cgi/content/short/1410083111 12 of 12

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Dataset S1.1(a). List of positively selected genes identified by the two-branch
and branch-site tests in the Carnivore lineage

Dataset S1.1(b). List of positively selected genes identified by the two-branch
and branch-site tests in the Carnivore lineage
MRPS12
NMI
PDE4C
PPP1R3A
RELL2
SHARPIN
SNAPC4
THADA
TP53BP1
VRK2
MSMP
NODAL
PDE6B
PRC1
RGS4
SHC4
SNAPC5
THBS3
TPX2
WFDC11
MSR1
NOL7
PDILT
PRF1
RHBDD1
SIGIRR
SNCAIP
THSD1
TRA2A
YIPF3
MUM1L1
NOV
PEX6
PRICKLE2
RHCG
SKAP2
SNRNP25
TK2
TRAF7
ZC3HAV1
MUTYH
NSD1
PGLYRP1
PSD3
RHEBL1
SLC10A4
SOAT1
TLR2
TRDMT1
ZMYM3
MYD88
NSUN5
PGM2
PSMD6
RHOT2
SLC12A4
SOCS6
TLR4
TREM2
ZNF331
MYH8
NUP153
PHF15
PTCD2
ROS1
SLC13A2
SPATA7
TLR6
TRIM25
ZNF398
MYO15A
OAZ3
PIBF1
PTGR1
RRAGD
SLC15A1
SPTA1
TLR8
TRIM33
ZNF473
MYO3B
OAZ3
PIGQ
PTPRC
RRS1
SLC16A5
SRGN
TMCO6
TSEN2
ZNF687
MYO7A
OBFC1
PIK3CB
PTPRH
RSPO4
SLC22A23
SS18L1
TMEM109
TSHZ2
ZNF777
NANOS3
OIT3
PITPNA
PXN
RTBDN
SLC22A8
ST3GAL1
TMEM116
TSPAN10
ZSWIM5
NBEAL1
OLFM1
PITX1
PYCARD
RTN4
SLC25A23
STK24
TMEM150B
TSPYL4
NDOR1
OR10V1
PKHD1
QSER1
RTP3
SLC25A42
SUCLG1
TMEM156
TTC34
NDST3
OR13H1
PKMYT1
RAB11FIP5
SCGB1C1
SLC29A2
TAL2
TMEM167B
TTF2
NDUFA6
OSGEP
PLA2G2F
RAB18
SCML2
SLC2A10
TAS2R38
TMEM176A
TUBGCP3
NDUFAF4
OSMR
PLBD1
RAB19
SCN3B
SLC44A4
TBC1D21
TMEM182
UBA7
NDUFV2
OTOF
POC1B
RAD52
SCNM1
SLC47A1
TBL3
TMEM215
UBE2L6
NFAM1
OTUB2
PPA2
RAG1
SDR39U1
SLC4A1
TBXAS1
TMIGD1
UGT2A3
NGLY1
OVCA2
PPEF1
RANGAP1
SEC61A2
SLC4A5
TCN2
TMOD1
UMOD
NGRN
OXCT1
PPID
RASAL1
SEL1L2
SLC6A4
TEP1
TMX1
UNC13D
NID1
PADI2
PPL
RASSF5
SELP
SLC7A1
TFAM
TNFRSF13B
UPRT
NIN
PCDH12
PPM1E
RCSD1
SEPT12
SLC7A4
TFB2M
TNKS1BP1
UTP11L
NKTR
PCNXL2
PPM1K
RECQL4
SERPINB9
SLCO1C1
TG
TOM1
VAMP8
NLRP14
PDCL3
PPP1R2
REEP1
SH2D2A
SMPDL3B
TGM6
TOX4
VPS13C

ABCA5
BAK1
C5
CHRD
DNAJB4
GMIP
IPO7
LRRC14B
N4BP2
PRX
ACADL
BBS7
CA4
CLEC5A
DNHD1
GPA33
IQCH
LRRC6
NIF3L1
PSMB8
ACCS
BBS9
CALML5
CLUL1
DUSP2
GPAA1
IRF8
LRRTM2
NOLC1
PSME3
ACSF3
BCAT2
CAPN13
CMTM2
DYSF
GPRIN3
IRS4
LTA4 H
NPNT
PSMG3
ADAM22
BCL2L14
CATSPER3
CMYA5
E2F7
GRIA2
ISG15
LY9
NPY
PTPRC
ADC
BCL2L15
CCDC107
CNKSR1
ECM2
GRIA2
ITGAE
MAMDC2
NPY1R
PTPRH
AHSP
BIN1
CCDC112
CRTAM
EFCAB2
GRIN2C
ITGB7
MAP7D3
NTRK1
PTPRN
AIM1L
BIRC3
CCDC113
CST7
EHBP1L1
GSDMC
ITIH4
MAPK8IP2
NUBP2
PTPRQ
AKAP9
BMF
CCDC150
CTSZ
EHHADH
GTPBP8
ITPR3
MAPKBP1
NUDCD3
RAB20
AKNA
BMP15
CCNE2
CTTNBP2NL
EPHX1
GUCA1A
KIF1A
MCM7
NUDT22
RASGRP1
AKNAD1
BMPR2
CD200
CXorf23
FA2 H
HAUS5
KREMEN2
MECR
OAZ3
RBM28
ALB
BPI
CD244
CXorf57
FAIM3
HCFC2
L1CAM
MEIS1
OMA1
RELA
ALDH1A2
BRD7
CD274
CYP17A1
FAM161B
HDGF
LARS2
MKNK2
OOEP
RIBC1
ALG3
BRIP1
CD48
CYP1A2
FAM181A
HFM1
LAT2
MORN3
PARP2
RNF141
ALPK2
BRWD1
CD8B
DCST2
FBN3
HHIPL2
LAX1
MRPL50
PC
RNF217
ANGPT2
C10orf137
CD97
DDO
FIGF
HSD17B14
LCNL1
MRPL55
PFN2
RNPEP
ANKS4B
C12orf56
CDC25B
DDX49
FKBP3
HSPBP1
LGALS2
MSGN1
PIK3C2G
ROS1
ANPEP
C14orf166B
CDH1
DEPDC1
FKBP4
IFNK
LIMS2
MTRR
PLAC8L1
RPUSD4
AP3B2
C17orf64
CDH17
DEPDC7
FKBP7
IGF1
LIN28B
MUTYH
PNLIP
RSPH6A
ARF4
C1orf146
CDH5
DHRS1
GAP43
IGFBP5
LMBRD2
MVK
PPAPDC1A
S100A12
ARMCX2
C1orf194
CDKN1B
DHX32
GGA3
IL17RB
LMF1
MYH8
PPP1R13L
SACS
ATE1
C1QB
CEACAM18
DLGAP5
GJA10
IL22
LONRF3
MYO15A
PRF1
SCAMP2
ATP2B3
C2orf43
CENPE
DMP1
GJA5
INHBB
LPAR5
MYO1F
PROM1
SCAP
AZGP1
C3orf62
CES2
DNAH8
GLIPR1L2
INVS
LRAT
MYO7A
PRRG3
SCD5
Dataset S1.2(a). List of positively selected genes identified by the two-branch
and branch-site tests in the Felidae lineage

SCG2
SLC16A5
SNCG
STARD13
TDG
TMEM176A
TRAT1
UBE2S
WRN
ZSWIM2
SCGB1A1
SLC1A7
SNRNP70
STARD3
TEX11
TMEM19
TRMU
UCHL1
XKR7
SDC2
SLC27A1
SPATA7
STK31
TFAP2A
TMEM190
TRPM4
UMPS
XRCC5
SELL
SLC2A4
SPEF2
STOX1
TGM7
TMEM211
TRPS1
UNC93B1
YIF1B
SERHL2
SLC38A8
SPHK1
SVEP1
THTPA
TMX3
TSPAN8
USHBP1
ZFYVE16
SF3A2
SLC43A3
SPTBN4
SYDE2
TM6SF2
TNFAIP3
TSSK4
VTI1A
ZNF304
SFTPB
SLC7A11
SPTBN5
SYNM
TMEM140
TNIP2
TTC34
WDFY4
ZNF408
SH2D2A
SLCO2B1
SPTLC3
SYTL3
TMEM150B
TNIP3
TTC39C
WFDC8
ZNF780B
SIPA1L2
SMOC2
SRCRB4D
TAPBPL
TMEM156
TRA2A
TTYH1
WHAMM
ZNF804B
SIT1
SNAPC3
STAM
TCF3
TMEM161B
TRAF3IP2
TUSC5
WIPF2
ZSCAN29
Dataset S1.2(b). List of positively selected genes identified by the two-branch
and branch-site tests in the Felidae lineage

ABHD1
BRAF
CENPM
ENKUR
GPR174
ITGA9
MIIP
OR2B11
PSPH
SERINC3
ACOT11
BRCA1
CEP68
ENTPD7
GPRASP2
ITGBL1
MORC1
OR4D6
PSTK
SH2D5
ACOT13
C11orf54
CEP97
EPHB4
GPRC5A
ITPR3
MRPL11
OTOF
PTPRR
SHC4
ACOT8
C11orf63
CHMP4B
ETV4
GPRIN2
JMJD1C
MRPL52
PAFAH2
PTPRS
SIAE
ACOX2
C16orf71
CIB4
FAIM3
GRHL3
KIAA0226
MTIF2
PARV G
PUSL1
SLC22A13
ACOX3
C1orf109
CLDN17
FAM131B
GRIA2
KIF1C
MTRF1
PCDHB4
RABL3
SLC22A18
ADAMDEC1
C22orf31
CLEC5A
FAM179A
HADH
KIF22
MURC
PHLDB3
RBM11
SLC25A38
ADAMTS13
C2orf40
CNGA2
FAM69A
HEATR5B
KIF27
MVK
PITRM1
RBP5
SLC35F5
ADAMTSL3
C2orf62
COL6A3
FAN CB
HECA
KIRREL2
MYLK3
PJA 2
RCSD1
SLC39A7
AK1
C3orf62
COL9A3
FAT4
HEPACAM2
KRIT1
MYO15A
PLA2G2E
RELL1
SLC39A8
ALDH16A1
C8B
CROCC
FBN3
HEPH
KYNU
MYO9A
PLA2G3
RHBDD1
SLC46A1
ALS2CR12
C9orf96
CSPP1
FBXL22
HMMR
LAMC2
NAPRT1
PLAC1
RIMKLA
SLCO1A2
AMACR
CAGE1
CTTN
FBXO28
HPS5
LAP3
NEK1
PLAC8L1
RNASE6
SMG1
ANKRD2
CASP7
CYB5R1
FER
HSD3B7
LATS2
NEK4
PLIN3
RNPC3
SMG6
ANKRD49
CBX2
CYP27B1
FGA
HSPA13
LCAT
NFAM1
PML
RSL1D1
SPATA21
ANKRD50
CCDC38
DACT1
FN3K
IFT81
LIAS
NFKBIZ
PPAP2A
RTP3
SPATA7
APEH
CCDC64B
DAPK1
FRMD7
IGHMBP2
LIMD1
NOLC1
PPAPDC1B
S100A12
SPERT
APOBEC4
CCDC70
DNAJB9
GCNT7
INHBC
LRRC32
NOSTRIN
PPFIBP1
SCN9A
SPHKAP
ARHGAP26
CD27
DNTTIP2
GEMIN7
INPP4B
LRRC36
NOTCH2
PPP1R13B
SCRIB
SPINT1
ASB11
CD48
DPEP3
GGT6
INPP5J
LSM3
NPFFR2
PRICKLE4
SDK2
SPTBN5
ATXN7L1
CD93
DUSP19
GOLGA1
IPO4
MAP7D2
NRG2
PRKAG1
SEC24A
SREBF1
BARD1
CDH6
ECHDC1
GPATCH8
IQCB1
MARVELD3
NUDT15
PRKG2
SENP5
SRRM2
BCAP31
CELA1
EDC3
GPR133
ISG15
MERTK
OPTC
PRR11
SENP7
STARD5
BPI
CENPE
EHBP1L1
GPR15
ITGA2B
METTL8
OR10K1
PRX
SEPT10
STK11IP
Dataset S1.3(a). List of positively selected genes identified by the two-branch
and branch-site tests in the Felinae lineage

STS
TAS2R1
THUMPD1
TRPV6
UBXN10
WDR62
WWC1
ZMYND10
ZZEF1
SUN3
TAS2R3
TMEM59L
TSTD2
USP45
WDR90
XCR1
ZNF436
SURF2
TEX14
TMEM71
TXN2
UVRAG
WFDC8
XPC
ZNF555
SYNM
TF
TOE1
TXNRD2
VEZT
WIPF2
ZFAT
ZNF622
SYTL1
THBS2
TP53BP1
TYK2
WDR17
WIPF3
ZFYVE19
ZNF780B
Dataset S1.3(b). List of positively selected genes identified by the two-branch
and branch-site tests in the Felinae lineage

Gene Name
Number of Significant
Amino Acid Properties
Identified Categories
Intense Protein
Functional Changes
Number of Suggested
Deleterious Amino
Acid Substitutions
ABHD1
2
9,22
negative
0
ACOT11
3
12,17,26
negative
0
ACOT8
1
9
negative
0
ACOX2
5
7,10,12,15,31
negative
0
ACOX3
6
4,10,12,15,17,21
positive
2
AMACR
5
10,17,24,30,31
positive
4
BARD1
2
9,12
negative
0
BBS7
0
negative
0
BBS9
2
3,7
negative
0
BRAF
2
9,22
positive
1
BRCA1
28
1-9,11-15,17-26,28-31
positive
11
CA4
2
13,27
positive
1
CABP4
0
negative
0
CDKN1B
0
negative
0
CHM
4
1,4,11,12
negative
0
CNGA2
2
10,15
positive
1
CNGB3
1
31
positive
1
COL6A3
31
1-31
positive
1
COL9A3
4
13,15,17,31
positive
1
CPLX4
0
negative
0
CYP27B1
1
17
negative
0
GJA10
0
positive
1
GRIA2
1
2
positive
2
GRIN2C
2
9,17
negative
0
GUCA1A
0
negative
0
GUCA1B
0
negative
0
HADH
1
28
negative
0
HMMR
5
1,7,9,15,17
positive
2
HSD3B7
2
9,15
negative
0
IMPG1
0
negative
0
INPP5J
4
1,2,4,12
negative
0
IQCB1
2
15,22
negative
0
ITGA2B
14
3,6,7,8,10,12,16,17,19,22,24,28,29,31
negative
0
ITGA9
3
1,3,15
negative
0
LAMC2
14
3,7-10,12,13,15,16,17,19,26,29,31
positive
1
LCAT
0
negative
0
LRAT
0
negative
0
1
Significant genes common to both approaches are highlighted in red.
a- TreeSAAP is used to measure structural and biochemical properties of amino acid replacement using a threshold of P<0.001. 31
categories are tested as follows: 1. Alpha-helical tendencies, 2. Average number of surrounding residues, 3. Beta-structure tendencies, 4.
Bulkiness, 5. Buriedness, 6. Chromatographic index, 7. Coil tendencies, 8. Composition, 9. Compressibility, 10. Equilibrium constant, 11.
Helical contact area, 12. Hydropathy, 13. Isoelectric point, 14. Long-range non-bonded energy, 15. Mean r.m.s. fluctuation displacement, 16.
Molecular volume, 17. Molecular weight, 18. Normalized consensus hydrophobicity, 19. Partial specific volume, 20. Polar requirement, 21.
Polarity, 22. Power to be at the C-terminal, 23. Power to be at the middle of alpha-helix, 24. Power to be at the N-terminal, 25. Refractive index,
26. Short and medium range non-bonded energy, 27. Solvent accessible reduction ratio, 28. Surrounding hydrophobicity, 29. Thermodynamic
transfer hydrohphobicity, 30. Total non-bonded energy, 31. Turn tendencies
b - Amino acid substitutions labeled as “deleterious” based on Provean.
Dataset S1.4(a). Predicted structural/functional influence of the domestic cat
nonsynonymous substitutions for positively selected sensory and lipid
metabolism genes

Gene Name
Number of Significant
Amino Acid Properties
Identified Categories
Intense Protein
Functional Changes
Number of Suggested
Deleterious Amino
Acid Substitutions
MERTK
2
9,17
negative
0
MKKS
3
3,4,25
negative
0
MVK
27
1-6,8-19,20,21,22,25-30
negative
0
MYLK3
0
negative
0
MYO15A
17
1,4,5,9,12,14-17,19,20-23,26,30,31
positive
2
MYO3B
0
positive
1
MYO7A
5
7,9,12,17,26
positive
2
MYO9A
13
1,3,10-13,15,16,17,19,20,22,31
positive
3
NPFFR2
4
11,16,19,26
positive
1
NPY
0
negative
0
NPY1R
0
negative
0
OR10K1
2
3,22
positive
2
OR10V1
2
9,17
negative
0
OR13H1
0
negative
0
OR2B11
1
15
positive
1
PAFA H 2
2
12,15
negative
0
PARVG
1
12
negative
0
PCDH4B
0
negative
0
PDE6B
2
15,26
negative
0
PLA2G2E
4
9,17,26,27
negative
0
PLA2G3
1
17
positive
2
PPAP2A
2
5,26
positive
4
PPAPDC1B
1
9
negative
0
PPEF1
6
4,11,15,22,23,28
negative
0
PRKAG1
0
negative
0
PRKG2
0
negative
0
PROM1
16
3,4,6,7,8,11,14-17,20,22,23,28,30,31
positive
6
PTPRQ
25
2-17,19,21,22,23,27~31
positive
4
RTP3
1
1
positive
1
SHC4
0
negative
0
SIAE
2
9,24
positive
1
SLCO1A2
5
7,10,11,16,23
negative
0
SMG1
12
3,10,11,12,14-17,22,23,24,29
negative
0
STARD5
1
9
negative
0
TAS2R3
10
2,3,5,8,10,12,18,19,25,30
positive
3
TAS2R38
11
3,5,6,7,8,10,11,15,26,30,31
positive
1
THBS2
12
2,3,7-11,15,17,22,26,31
negative
0
1
Dataset S1.4(b). Predicted structural/functional influence of the domestic cat
nonsynonymous substitutions for positively selected sensory and lipid
metabolism genes
Significant genes common to both approaches are highlighted in red.
a- TreeSAAP is used to measure structural and biochemical properties of amino acid replacement using a threshold of P<0.001. 31
categories are tested as follows: 1. Alpha-helical tendencies, 2. Average number of surrounding residues, 3. Beta-structure tendencies, 4.
Bulkiness, 5. Buriedness, 6. Chromatographic index, 7. Coil tendencies, 8. Composition, 9. Compressibility, 10. Equilibrium constant, 11.
Helical contact area, 12. Hydropathy, 13. Isoelectric point, 14. Long-range non-bonded energy, 15. Mean r.m.s. fluctuation displacement, 16.
Molecular volume, 17. Molecular weight, 18. Normalized consensus hydrophobicity, 19. Partial specific volume, 20. Polar requirement, 21.
Polarity, 22. Power to be at the C-terminal, 23. Power to be at the middle of alpha-helix, 24. Power to be at the N-terminal, 25. Refractive index,
26. Short and medium range non-bonded energy, 27. Solvent accessible reduction ratio, 28. Surrounding hydrophobicity, 29. Thermodynamic
transfer hydrohphobicity, 30. Total non-bonded energy, 31. Turn tendencies
b - Amino acid substitutions labeled as “deleterious” based on Provean.

Dataset S1.5. Enriched pathways among genes under positive selection in the
domestic cat (Felinae) lineage
PATHWAY COMMONS CATEGORY
C
O
E
GENES
BETA-OXIDATION OF PRISTANOYL-COA
8
4
0.11
ACOX2, AMACR, ACOX3, ACOT8
BILE ACID AND BILE SALT METABOLISM
27
5
0.37
SLCO1A2, ACOX2, AMACR, HSD3B7,
ACOT8
SYNTHESIS OF BILE ACIDS AND BILE SALTS
VIA 7ALPHA-HYDROXYCHOLESTEROL
15
4
0.21
ACOX2, AMACR, HSD3B7, ACOT8
PEROXISOMAL LIPID METABOLISM
20
4
0.28
ACOX2, AMACR, ACOX3, ACOT8
METABOLISM OF LIPIDS AND
LIPOPROTEINS
258
12
3.57
LCAT, CYP27B1, PPAP2A, SLCO1A2,
MVK, HADH, STARD5, ACOX2,
AMACR, ACOX3, HSD3B7, ACOT8
KEGG CATEGORY
ECM-RECEPTOR INTERACTION
85
6
1.18
HMMR, ITGA9, THBS2, LAMC2,
ITGA2B, COL6A3
LONG-TERM DEPRESSION
70
6
0.97
PRKG2, PLA2G2E, BRAF, GRIA2,
ITPR3, PLA2G3
PRIMARY BILE ACID BIOSYNTHESIS
16
3
0.22
ACOX2, AMACR, HSD3B7
ETHER LIPID METABOLISM
36
4
0.5
PLA2G2E, PPAP2A, PAFAH2, PLA2G3
FOCAL ADHESION
200
9
2.77
SHC4, BRAF, PARVG, MYLK3,
ITGA9, THBS2, LAMC2, ITGA2B,
COL6A3
ALPHA-LINOLENIC ACID METABOLISM
20
3
0.28
PLA2G2E, ACOX3, PLA2G3
PEROXISOME
79
5
1.09
ACOX2, MVK, AMACR, ACOX3,
ACOT8
GO CATEGORY
LIPID MODIFICATION
143
11
2.16
LCAT, PPAP2A, HADH, PRKAG1,
ACOX2, AMACR, INPP5J, ACOX3,
SMG1, PPAPDC1B, ACOT8
FATTY ACID BETA-OXIDATION USING
ACYL-COA OXIDASE
11
4
0.17
ACOX2, AMACR, ACOX3, ACOT8
CARBOXYLIC ESTER HYDROLASE
ACTIVITY
116
8
1.71
LCAT, PAFAH2, ACOT11, PLA2G2E,
SIAE, ABHD1, PLA2G3, ACOT8
PRISTANOYL-COA OXIDASE ACTIVITY
2
2
0.03
ACOX2, ACOX3
BRCA1-BARD1 COMPLEX
2
2
0.03
BRCA1, BARD1
USER DATA & PARAMETERS - N = 281 genes submitted, Genes mapped to unique Entrez Gene IDs: 281,
Organism: hsapiens, Id Type: gene_symbol, Ref Set: entrezgene_protein-coding, Significance Level: .05,
Statistics Test: Hypergeometric, MTC: BH, Minimum: 2
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and
also in the category (O), expected number in the category (E).
1

GO CATEGORY
PATHWAY ID
C
O
E
R
rawP
adjP
pattern recognition receptor activity
GO:0008329
15
4
0.39
10.29
0.0005
0.0482
glycosaminoglycan binding
GO:0005539
174
13
4.51
2.88
0.0006
0.0482
diacyl lipopeptide binding
GO:0042498
2
2
0.05
38.60
0.0007
0.0482
secondary active oligopeptide transmembrane
transporter activity
GO:0015322
2
2
0.05
38.60
0.0007
0.0482
bacterial cell surface binding
GO:0051635
17
4
0.44
9.08
0.0008
0.0482
proton-dependent oligopeptide secondary active
transmembrane transporter activity
GO:0005427
2
2
0.05
38.60
0.0007
0.0482
carbohydrate derivative binding
GO:0097367
189
14
4.90
2.86
0.0004
0.0482
cytoplasmic part
GO:0044444
6728
210
170
1.23
5.38E-05
0.0157
plasma membrane part
GO:0044459
1908
72
48.38
1.49
0.0003
0.0292
intrinsic to plasma membrane
GO:0031226
1255
53
31.82
1.67
0.0002
0.0292
integral to plasma membrane
GO:0005887
1214
49
30.78
1.59
0.0008
0.0389
Toll-like receptor 2-Toll-like receptor 6 protein
complex
GO:0035355
2
2
0.05
2.41
0.0008
0.0389
mitochondrial matrix
GO:0005759
278
17
7.05
2.41
0.0008
0.0389
cytoplasm
GO:0005737
9051
261
229.5
1.14
0.001
0.0417
membrane
GO:0016020
7631
224
193.5
1.16
0.0015
0.0487
cell periphery
GO:0071944
4286
136
108.68
1.25
0.0015
0.0487
USER DATA & PARAMETERS - N = 467 genes submitted, Genes mapped to unique Entrez Gene IDs: 466, Organism: hsapiens, Id
Type: gene_symbol, Ref Set: entrezgene_protein-coding, Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH,
Minimum: 2
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category (O),
expected number in the category (E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted by the
multiple test adjustment (adjP).
Dataset S1.6. Enriched gene ontology categories among genes under positive
selection in Carnivora

PATHWAY COMMONS
Pathway ID
C
O
E
R
rawP
adjP
AlphaE beta7 integrin cell surface interactions
1632
3
3
0.5
61.46
4.27E-06
0.0012
Adaptive Immune System
515
237
14
3
3.63
3.64E-05
0.0049
Immunoregulatory interactions between a
Lymphoid and a non-Lymphoid cell
1098
52
6
0.82
7.09
0.0002
0.0180
Immune System
522
522
20
8.49
2.35
0.0004
0.027
Interaction between L1 and Ankyrins
45
12
3
0.2
15.37
0.0008
0.0432
KEGG CATEGORY
Cell adhesion molecules (CAMs)
4514
133
9
2.16
4.16
0.0003
0.0246
GO CATEGORY
epoxide hydrolase activity
GO:0004301
5
3
0.09
33.78
5.40E-05
0.0155
ether hydrolase activity
GO:0016803
7
3
0.12
24.13
0.0002
0.0287
external side of plasma membrane
GO:0009897
199
12
3.42
3.51
0.0002
0.0442
USER DATA & PARAMETERS - N = 331 genes submitted, Genes mapped to unique Entrez Gene IDs: 331, Organism: hsapiens, Id
Type: gene_symbol, Ref Set: entrezgene_protein-coding, Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH,
Minimum: 2
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category
(O), expected number in the category (E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted
by the multiple test adjustment (adjP).
Dataset S1.7. Enriched gene ontology categories among genes under positive
selection in Felidae

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M !>?,I@@JK@@@LACBCJ=
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M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@A=JJL
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@ACKCK
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AJBK@
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@ABKBB
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AKKJ@
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AJB=B
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@CLA<A
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@ACCCA
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@ACAJB
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AC<AC
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@ACKAN
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@C@<L@
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AN==@
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AAC=J
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AJ==@
M !>?,I@@JK@@@LACBCJ=
!>?,9:)@@@@@@AA=AB
D!:EF(E !>?,I@@JK@@@LACBJ<C
!>?,9:)@@@@@@A<@L@
*)(D!:EF(9D:*>(E(*(G!)*H> !>?,I@@JK@@@LACBJ=B
!>?,9:)@@@@@@AAKK=
M !>?,I@@JK@@@LACBJ=B
!>?,9:)@@@@@@ACCAN
M !>?,I@@JK@@@LACBJ=B
!>?,9:)@@@@@@AA@KL
O>P>HQ> !>?,I@@K@@@@L<@J<@@
88888888888888888888888888
Dataset S1.8(a). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-./
$01#!"2///////3/4/
5$56+,78%59:878%!+1%69"01%+1:;$9"1$%%3%
55+"1$%$!<=>?>3>@%9:6";"1$
$01#;//=/////?A/@=.
$01#!"2///////=BAB
C $01#;//=/////?A3?=D
$01#!"2//////?@//@
C $01#;//=/////?A?/4/
$01#!"2///////D3@?
C $01#;//=/////?.4@.3
$01#!"2///////@43/
C $01#;//=/////?.4@.3
$01#!"2///////./?A
5$56+,78%59:878%!+1%69"01%+1:;$9"1$%
55+"1$%$!<=>?>3>@%!7!8:5E+8+0%!7!8:15:9+0%
"%F+0,+02%9:6";"1$
$01#;//./////4?33BD
$01#!"2///////43=4
C $01#;//./////4?33BD
$01#!"2//////?B3D/
C $01#;//./////4?33BD
$01#!"2//////?@/4D
C $01#;//./////4?33BD
$01#!"2//////?@?./
C $01#;//./////4?33BD
$01#!"2//////B/=?B
C $01#;//./////4?33BD
$01#!"2//////?ABDD
C $01#;//./////4?33BD
$01#!"2//////?@B3D
C $01#;//./////4?33BD
$01#!"2//////?4@A@
C $01#;//./////4?33BD
$01#!"2//////B/34B
C $01#;//./////4?33BD
$01#!"2//////?@=A@
C $01#;//./////4?33BD
$01#!"2//////3?B?.
C $01#;//./////4?33BD
$01#!"2//////?.?3.
C $01#;//./////4?33BD
$01#!"2//////?==DB
C $01#;//./////4?33BD
$01#!"2//////??33=
C $01#;//./////4?33BD
$01#!"2////////@33
5$56+,78%59:878%!+1%69"01%+1:;$9"1$%
55+"1$%$!<=>?>3>@%9:6";"1$
$01#;//A3///3DD3ADD
$01#!"2//////??@A/
C $01#;//A3///3DD3ADD
$01#!"2//////?@.3=
C $01#;//A3///3DD3ADD
$01#!"2//////?@4?.
C $01#;//A3///3DD3ADD
$01#!"2//////?@3.@
C $01#;//A3///3DD3ADD
$01#!"2///////4/=.
5$56+,7859:878%+1:;$9"1$%,:;"+0%"0,%
G,%9$5$"6%!:06"+0+02%3%$!<=>?>3>@
$01#;//=/////?A/B=A
$01#!"2//////?A4.B
9"0F5?%%"0,%29+5%,:;"+0%!:06"+0+02%9"0%
F+0,+02%?%%9"0F5?%%9"0F
$01#;//=/////?A/D??
HHHHHHHHHHHHHHHHHHHHHHHHHH
Dataset S1.8(b). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-..
$/0#!"122222222.34
,5/$+/%6$"75%!6"+/%"89/$:";%"89/$:";%
<$="%,5/$+/%6$"75%!6"+/%!+;+">5%,5/$+/%
6$"75%!6"+/
$/0#:22.?222?@@?A4B
$/0#!"12222222CB2B
D $/0#:22.?222?@@?A4B
$/0#!"12222222B@4.
D $/0#:22.?222?@@?A4B
$/0#!"122222224EB4
D $/0#:22.?222?@@?A4B
$/0#!"12222222E3C3
D $/0#:22.?222?@@?A4B
$/0#!"1222222??2A2
D $/0#:22.?222?@@?A4B
$/0#!"1222222??23C
D $/0#:22.?222?@@?A4B
$/0#!"1222222??EE.
D $/0#:22.?222?@@?A4B
$/0#!"1222222?@@?2
D $/0#:22.?222?@@?A4B
$/0#!"1222222?A?3B
D $/0#:22.?222?@@?A4B
$/0#!"1222222?AB@?
D $/0#:22.?222?@@?A4B
$/0#!"1222222?A.?2
D $/0#:22.?222?@@?A4B
$/0#!"1222222C@B.A
D $/0#:22.?222?@@?A4B
$/0#!"1222222B?4EC
D $/0#:22.?222?@@?A4B
$/0#!"1222222C4A.B
D $/0#:22.?222?@@?A4B
$/0#!"1222222B23?B
D $/0#:22.?222?@@?A4B
$/0#!"1222222CCE@2
D $/0#:22.?222?@@?A4B
$/0#!"1222222B2@?B
D $/0#:22.?222?@@?A4B
$/0#!"1222222CBE44
D $/0#:22.?222?@@?A4B
$/0#!"1222222C.2?4
D $/0#:22.?222?@@?A4B
$/0#!"1222222CAE@C
D $/0#:22.?222?@@?A4B
$/0#!"1222222CE3E3
D $/0#:22.?222?@@?A4B
$/0#!"1222222CA44@
D $/0#:22.?222?@@?A4B
$/0#!"1222222CE..C
,5/$+/%6$"75%!6"+/%?@%"89/$:";%
"89/$:";%<$="%,5/$+/%6$"75%!6"+/%?@%
!+;+">5%,5/$+/%6$"75%!6"+/%?@
$/0#:22CA22222?B4C?
$/0#!"1222222C.?32
F/G/9H/ $/0#:22.2222?@2B.CA
$/0#!"12222222B@42
F/G/9H/ $/0#:22.2222?BEAE2E
IIIIIIIIIIIIIIIIIIIIIIIIII
!"#$%#&'()*%+,-E3
$/0#!"1222222C@E?3
=%!$;;%>$!$J=9>%";J6"%!6"+/%7%>$1+9/%J5?@%
J>$!F>09>
$/0#:223.222?CBE3B2
$/0#!"1222222CAB@2
F/!6">"!=$>+K$,%#>"1:$/= $/0#:223.222?CB4?BB
$/0#!"1222222C4C33
D $/0#:223.222?C@2C?.
$/0#!"1222222C3@.3
D $/0#:223.222?CA.2@3
$/0#!"1222222B2?.4
D $/0#:223.222?C@@AEA
$/0#!"1222222B2A@2
F/G/9H/ $/0#:223.222?CB4B?@
$/0#!"1222222CB@?B
D $/0#:22.2222?@2B?23
$/0#!"1222222C4?CB
D $/0#:223.222?CB4B?@
IIIIIIIIIIIIIIIIIIIIIIIIII
Dataset S1.8(c). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-./0
$12#!"3///////0456
789$:81"2";%<=>$%.%:$!$><8:%7.:%%
:$!$><8:
$12#9//6?////.6/5?5
$12#!"3//////.406@
A $12#9//6?////.6/5?5
$12#!"3//////?@5/.
A $12#9//4B////.?@46?
$12#!"3//////?45@6
A $12#9//6?////.6/5?5
$12#!"3//////4/0B6
A $12#9//6?////.6/5?5
$12#!"3//////4/6@0
A $12#9//6?////.6/5?5
$12#!"3//////?B46B
A $12#9//6?////.6/5?5
$12#!"3//////?CBBB
A $12#9//5/////?0/000
$12#!"3//////?5B0/
A $12#9//5/////?0/000
$12#!"3//////4.655
A $12#9//6?////.6/5?5
$12#!"3//////?BBB6
A $12#9//6?////.6/5?5
$12#!"3//////?C.0.
A $12#9//5/////?@BB.B
$12#!"3//////?5@.B
A $12#9//6?////.6/5?5
$12#!"3//////??05.
A $12#9//6?////.6/5?5
$12#!"3//////4/B0.
A $12#9//6?////.6/5?5
$12#!"3//////4.C6.
A $12#9//50////C5./@6
$12#!"3//////?@05/
A $12#9//6?////.6/5?5
$12#!"3//////??@0/
A $12#9//6?////.6/5?5
$12#!"3////////.??
A $12#9//6?////.6/5?5
$12#!"3//////??@@C
A $12#9//5/////?0/000
$12#!"3//////?B?00
A $12#9//6?////.6/5?5
$12#!"3//////4../.
A $12#9//5/////?@BB.B
DDDDDDDDDDDDDDDDDDDDDDDDDD
!"#$%#&'()*%+,-.5B
$12#!"3///////?C/0
<:"12!:+><+81%#"!<8:%28E $12#9//5/////?@B056
$12#!"3///////6?.B
A $12#9//5/////?@B056
$12#!"3//////.5@C5
A $12#9//5/////?@B056
$12#!"3//////??@.4
A $12#9//@0///.?450./
$12#!"3///////B@.B
28E%.5 $12#9//5/////?06/?.
DDDDDDDDDDDDDDDDDDDDDDDDDD
!"#$%#&'()*%+,-4?4
$12#!"3///////.B5C
!8;;"3$1%";>F"%!F"+1%>:$!G:28: $12#9//?5///////?4.
$12#!"3///////6//5
A $12#9//?5///////?4.
$12#!"3///////B4C4
A $12#9//?5///////?4.
$12#!"3//////?@/4C
A $12#9//?5///////?4.
$12#!"3//////?B//0
A $12#9//?5///////?4.
$12#!"3//////?5/6?
A $12#9//?5///////?4.
$12#!"3//////4.@0.
G1H18I1 $12#9//0////.6/@..B
$12#!"3//////4/C@6
A $12#9//0////.6/0??B
$12#!"3//////?5/?4
A $12#9//0////.6/@.?.
DDDDDDDDDDDDDDDDDDDDDDDDDD
Dataset S1.8(d). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-./0
$12#!"344444445640
7+2891$%7/ $12#:44;<444/=50;0=
$12#!"344444440>;<
? $12#:44;<444/=50;0=
$12#!"34444444;4<>
? $12#:44;<444/=50;0=
$12#!"34444444;<;6
? $12#:44;<444/=50;0=
$12#!"3444444/0/<<
? $12#:44;<444/=50;0=
$12#!"344444440><4
7+2891$%7/8%8$28+!@A"B%7/%7+2891$ $12#:44;44444>====/
$12#!"344444440>;=
7+2891$%7/%/%7+2891$%7/" $12#:44;<444/=5</;<
$12#!"3444444=5;><
@1C19D1 $12#:44<4444/.4=./<
EEEEEEEEEEEEEEEEEEEEEEEEEE
!"#$%#&'()*%+,-.>.
$12#!"3444444=<65=
,+"F7"19@2%79:9A93%,+"F7"19@2%
B$A"8$,%#9B:+1
$12#:44=;4444404.=>
$12#!"34444445/4//
? $12#:44=;4444404.=>
$12#!"3444444=0;6<
? $12#:44=;4444404.=>
$12#!"3444444=</54
@1C19D1 $12#:44<4444/.4<.65
$12#!"34444445//>.
? $12#:44<4444/.4;5;.
$12#!"3444444=>.>;
? $12#:44<4444/.4545;
$12#!"3444444=>0>/
? $12#:44<4444/.4;5;;
$12#!"3444444=<464
? $12#:44<4444/.4;5;0
EEEEEEEEEEEEEEEEEEEEEEEEEE
!"#$%#&'()*%+,-04<
$12#!"34444444>/4.
F"B8+8+91+13%,$#$!8+G$%5%79:9A93%H%
":I98B9F7+!%A"8$B"A%2!A$B92+2%=%
!7B9:929:"A%B$3+91%!"1,+,"8$%3$1$%/>%
F"B5%H$8"%F"B8+8+91+13%,$#$!8+G$%5%%F"B5%A
$12#:44;/4444>0=6>/
$12#!"3444444=;56.
? $12#:44;/4444>0=6>/
$12#!"3444444=06=<
? $12#:44;/4444>0=6>/
$12#!"3444444==.>5
? $12#:44;/4444>0=6>/
$12#!"3444444=;<<5
? $12#:44;/4444>0=6>/
$12#!"3444444=06<4
? $12#:44;/4444>0=6>/
$12#!"3444444=..</
@1C19D1 $12#:44<4444/.45/0<
$12#!"3444444=<<<6
? $12#:44<4444/.4./6;
EEEEEEEEEEEEEEEEEEEEEEEEEE
Dataset S1.8(e). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-./0
$12#!"34444445..67
89:;+<+1%89:#+=>+<<">%;+;+1%%+3%,:8"+12%
;+;+1%+88?1:3<:=?<+1%,:8"+1
$12#844.744440.5660
$12#!"3444444@AB/0
C $12#844.744440.5660
$12#!"3444444@BB70
89:2+1%<+3D;%!D"+1%E+1"2$%28::;D%
8?2!<$%#>"38$1;%8<!E%$!F@G7G55G50
$12#844754445666.B6
$12#!"3444444@B4.@
89:2+1%<+3D;%!D"+1%E+1"2$%$!F@G7G55G50 $12#844..444476B5B.
$12#!"3444444B57@4
H"<<",+1 $12#844A/4445B.A7/0
$12#!"3444444@7@A@
C $12#844.744440.5755
$12#!"3444444@6A4A
C $12#844.744440.5755
$12#!"34444444B6@6
C $12#844.744440.5A7/
$12#!"3444444B5B56
?1E1:I1 $12#84474444564B46B
JJJJJJJJJJJJJJJJJJJJJJJJJJ
!"#$%#&'()*%+,-7.7
$12#!"3444444B4AA5
89:8$3"<+1%HD:2HD:,+$2;$>"2$%6,%
+1;$>"!;+13
$12#844@.4444445745
$12#!"3444444@A6..
C $12#844@.4444445745
$12#!"3444444@00A0
C $12#844@.4444445745
$12#!"3444444@BA57
C $12#844@.4444445745
$12#!"3444444B5067
C $12#844@.4444445745
$12#!"3444444@740A
C $12#844@.4444445745
$12#!"3444444B5A6@
1$?>:=<"2;:8"%=>$"EH:+1;%#"8+<9%
8$8=$>%A
$12#844.44444@0604@
$12#!"3444444B5B0@
?1E1:I1 $12#84474444564B@0B
JJJJJJJJJJJJJJJJJJJJJJJJJJ
!"#$%#&'()*%+,-7A6
$12#!"34444444.060
2$;%HD:2HD";"2$%@"%+1D+=+;:>%+@HH@"%+%
@HH@"%;$8H<";$%"!;+K";+13%#"!;:>%+%;"#%+
$12#844.44444@74@40
$12#!"34444444././
C $12#844.44444@74@40
$12#!"3444444@50/7
C $12#844.44444@74@40
$12#!"3444444@66B5
C $12#844.44444@74@40
$12#!"3444444B574.
C $12#844.44444@74@40
$12#!"3444444@67A@
C $12#844.44444@74@40
JJJJJJJJJJJJJJJJJJJJJJJJJJ
Dataset S1.8(f). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-./0
$12#!"30000000456/
7+$89%:;7$%<$!="192$12+:+>$%+91%!="11$?%
!9<791$1:%6%<$<@A"1$%+1,B!$,%@;%@$:"%
"<;?9+,%:A$":<$1:%<+@%#"<CD"
$12#<005/0000000ED5
$12#!"3000000C660/
F $12#<005/0000000ED5
$12#!"300000054..6
F $12#<005/0000000ED5
$12#!"30000005545G
F $12#<005/0000000ED5
$12#!"30000005ED.G
B1H19I1 $12#<00E00006G0C.E5
$12#!"30000005.GE.
F $12#<00E00006G0E646
JJJJJJJJJJJJJJJJJJJJJJJJJJ
!"#$%#&'()*%+,-604.
$12#!"30000000...D
1B!?$"A%A$!$7:9A%!9A$7A$229A%6%1%!9A%1%
!9A6
$12#<005/0000006650
$12#!"300000054D64
F $12#<005/0000006650
$12#!"3000000C056.
F $12#<005/0000006650
$12#!"30000005/GCG
F $12#<005/0000006650
$12#!"30000005E/E/
F $12#<005/0000006650
$12#!"30000005./05
F $12#<005/0000006650
$12#!"3000000C66.C
F $12#<005/0000006650
JJJJJJJJJJJJJJJJJJJJJJJJJJ
!"#$%#&'()*%+,-654G
$12#!"300000000.G/
$C%B@+KB+:+1%?+3"2$%A1#56C%$!L4MCM5MJ $12#<00GG00005C4.0E
$12#!"30000005G4C5
F $12#<00GG00005C4.0E
$12#!"300000055EDC
F $12#<00GG00005C4.0E
$12#!"3000000546.0
F $12#<00GG00005C4.0E
$12#!"300000055/ED
F $12#<00GG00005C4.0E
$12#!"30000005C5E.
F $12#<00GG00005C4.0E
$12#!"300000055.6/
F $12#<00GG00005C4.0E
$12#!"30000005G.40
B1H19I1 $12#<00E00006G05G6D
JJJJJJJJJJJJJJJJJJJJJJJJJJ
!"#$%#&'()*%+,-6ED/
$12#!"30000005E4G.
=$A>%ALEK56%5%7A9>+AB2%"1!$2:A"?%$1>%
79?;7A9:$+1%7A$!BA29A%$A>%C%$1>$?97$%
$A>C%$1>$?97$%$A>C%6%$1>$?97$%$1>$?97$%
79?;7A9:$+1%=$A>%A%$1>$?97$%$A>%A%
$1>$?97$%N!91:"+12%2BA#"!$%2B%O%
:A"12<$<@A"1$%:<%P
$12#<005/00000640ED
$12#!"30000005/D64
F $12#<005/00000640ED
$12#!"30000005EED4
F $12#<005/00000640ED
$12#!"30000005.4C5
F $12#<005/00000640ED
$12#!"30000005444.
F $12#<005/00000640ED
$12#!"3000000C6E4D
F $12#<005/00000640ED
Dataset S1.8(g). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!"#$%#&'()*%+,-../0
$12#!"344444456040
$7$2%289:%8;<;=;3%#>"3<$1:%$?+,$><"=%
3>;@:8%#"!:;>%%54%$3#%%54%$?+,$><"=%
3>;@:8%#"!:;>%%55%$3#%%55%2?"!$<"A$>%
8;<;=;3
$12#<44B044446B.4CC
$12#!"3444444./D56
E $12#<44CF4445DBCFD0
$12#!"3444444..//.
E $12#<44CF4445DBCFD0
$12#!"3444444D4CFD
$7$2%289: $12#<44B044446B5605
$12#!"3444444.//6.
E $12#<44B044446B5605
$12#!"3444444D4FDC
91A1;@1 $12#<44044445/4BD40
GGGGGGGGGGGGGGGGGGGGGGGGGG
!"#$%#&'()*%+,-.D66
$12#!"34444445D4D6
3=7!+1$%!=$"H"3$%272:$<%8%?>;:$+1%
<+:;!8;1,>+"=%?>$!9>2;>
$12#<44B44444.055C0
$12#!"3444444.B4CD
E $12#<44B44444.055C0
$12#!"3444444./0.5
91A1;@1 $12#<44044445/4/456
GGGGGGGGGGGGGGGGGGGGGGGGGG
!"#$%#&'()*%+,-./60
$12#!"34444445//BB
54%A,"%8$":%28;!A%?>;:$+1%
<+:;!8;1,>+"=%82?54I54%A,"%!8"?$>;1+1%
!8"?$>;1+1%54%!?154
$12#<44C04445.DB0BB
$12#!"3444444.6F0/
E $12#<44C04445.DB0BB
$12#!"3444444.B44B
91A1;@1 $12#<44044445/45.DC
$12#!"3444444./4FD
E $12#<44044445/45.DB
$12#!"3444444.DDDF
E $12#<44044445/45.D/
GGGGGGGGGGGGGGGGGGGGGGGGGG
!"#$%#&'()*%+,-./F5
$12#!"344444445F0D
=$9!+1$%>+!8%>$?$":%2$>+1$J:8>$;1+1$%
A+1"2$%5%$!K.I0I55I5
$12#<44.B44444450F/
$12#!"3444444D450D
91A1;@1 $12#<44044445/4D/FF
$12#!"3444444.0D.0
E $12#<44044445/450F5
GGGGGGGGGGGGGGGGGGGGGGGGGG
!"#$%#&'()*%+,-.B60
$12#!"3444444.D444
9L+M9+:+1%!">L;N7=%:$><+1"=%87,>;="2$%
/4%$!KDI/I5FI5.%,$9L+M9+:+1":+13%$1O7<$%
/4%9L+M9+:+1%:8+;$2:$>"2$%/4%9L+M9+:+1%
2?$!+#+!%?>;!$22+13%?>;:$"2$%/4
$12#<44.B444444B/44
$12#!"3444444.B0C/
E $12#<44.B444444B/44
$12#!"3444444.60C6
E $12#<44.B444444B/44
GGGGGGGGGGGGGGGGGGGGGGGGGG
!"#$%#&'()*%+,-.C5/
$12#!"34444444B06B
1;12$12$%.%9?%#>"<$28+#:%29??>$22;>%. $12#<44.B444444.D/C
$12#!"3444444D4BBC
E $12#<44.B444444.D/C
$12#!"3444444./00/
E $12#<44.B444444.D/C
Dataset S1.8(h). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

!!!!!!!!!!!!!!!!!!!!!!!!!!
"#$%&$'()*+&,-./0/1
%23$"#4555555/65/0
372#89:2%;#<&":;8<%=&>&3"8&> %23$;55/1555555?@51
%23$"#4555555///?/
A %23$;55/1555555?@51
%23$"#4555555/B>0B
A %23$;55/1555555?@51
!!!!!!!!!!!!!!!!!!!!!!!!!!
"#$%&$'()*+&,-./06>
%23$"#45555555@C>>
9D#23"D,89,:2&%<:24#9,:2&$#"9:D&E&
8:<78%89,-%&/&%<:24,2&>0&F-#&3GEG2,9&
%<:24,2&E&%<:E&D2#&8:<7;%D#3%&,,&
9D#23"D,89,:2&$#"9:D&3,,,&3GEG2,9&E&3,,,&8>0
%23$;55155555/C6??@
%23$"#4555555/BB65
A %23$;55155555/C6??@
%23$"#4555555/?6/C
A %23$;55155555/C6??@
!!!!!!!!!!!!!!!!!!!!!!!!!!
"#$%&$'()*+&,-.65@/
%23$"#4555555/?C1C
":,<%-&":,<&-:;#,2&":29#,2,24&>?0 %23$;551C555501/5?>
%23$"#4555555//?1C
A %23$;551C555501/5?>
%23$"#4555555/6>C6
G2F2:H2 %23$;55C5555>@5@>0>
!!!!!!!!!!!!!!!!!!!!!!!!!!
"#$%&$'()*+&,-.B0/C
%23$"#45555555>?>C
39%<<#&$D#4;%29 %23$;55?0555>6516B1
%23$"#4555555/?C5?
A %23$;55?0555>6516B1
%23$"#4555555/?>@B
G2F2:H2 %23$;55C5555>@5/161
Dataset S1.8(i). Felis catus gene members that underwent rapid gene family
expansions along the Felidae lineage.

Dataset S1.9. Summary of 1-Kbps windows, copy number distribution in control
regions and gain/loss cutoffs for the domestic cat (Abyssinian sample)
Sequencing
Sequencing technology
Illumina
# Reads
1,485,609,004
Coverage
21.8X
1-Kbps windows
# Total windows
1,122,501
# Control windows
993,102
# Non control windows
129,399
Gain/loss cutoffs
Mean copy number in control regions
2
StDev copy number in control regions
0.24
(# windows excluded*)
9,932
Gain cutoff
2.71
Loss cutoff
1.29
*1-Kbps windows exceeding the 1% highest copy number value

Dataset S1.10. Summary of duplications and deletions using sample-specific
gain/loss cutoffs based on the copy number distribution from the control
regions within the domestic cat genome (Abyssinian sample)
Duplications
# Duplications
85
# Duplications (gaps removed)
1002
# Bps*
9,065,598
% size of autosomes
0.39
# Bps in shared duplications*
4,377,574
% of duplicated bps
48.29
Deletions
# Deletions
1
# Deletions (gaps removed)
18
# Bps*
54,896
% size of autosomes
<0.01
# Bps in shared deletions*
0
% of deleted bps
0
*All bps are after excluding the size of the gaps (M1 method)

Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
A2
1999024
2024218
ENSFCAG00000026539
ZNF77
zinc finger protein 77
A2
2178186
2233965
ENSFCAG00000026952
A2
4837081
4840788
ENSFCAG00000022669
A2
4850030
4850775
ENSFCAG00000027538
A2
4879236
4926614
ENSFCAG00000005041
A2
4940497
4947843
ENSFCAG00000024220
A2
4951852
4957168
ENSFCAG00000024591
A2
10342173
10343114
ENSFCAG00000027467
A2
10403957
10404904
ENSFCAG00000024728
A2
10424192
10425154
ENSFCAG00000026934
A2
10444212
10445147
ENSFCAG00000028346
A2
10454027
10454932
ENSFCAG00000026032
A2
10465336
10466262
ENSFCAG00000030313
A2
10484879
10486405
ENSFCAG00000030477
A2
10503936
10505982
ENSFCAG00000022920
A2
10557343
10558290
ENSFCAG00000031912
A2
10561828
10562778
ENSFCAG00000029420
A2
10571496
10572431
ENSFCAG00000030284
A2
10588491
10589447
ENSFCAG00000027325
A2
10608719
10609642
ENSFCAG00000029342
A2
10637607
10639184
ENSFCAG00000025226
A2
10666812
10667738
ENSFCAG00000026535
A2
10677429
10678364
ENSFCAG00000027309
OR7C1
olfactory receptor, family 7, subfamily C, member 1
A2
10691698
10693042
ENSFCAG00000024926
A2
10735731
10736645
ENSFCAG00000025361
A2
10749819
10750754
ENSFCAG00000028413
A2
10774323
10775967
ENSFCAG00000026904
A2
10802221
10803189
ENSFCAG00000030343
A2
10811748
10813240
ENSFCAG00000031709
A2
11305320
11311224
ENSFCAG00000025482
A2
11312522
11362773
ENSFCAG00000008623
CYP4F3
cytochrome P450, family 4, subfamily F, polypeptide 3
A2
11380632
11382628
ENSFCAG00000031558
A2
11390153
11391070
ENSFCAG00000024776
A2
11408178
11409176
ENSFCAG00000029860
A2
11427607
11428557
ENSFCAG00000029127
A2
11444217
11445483
ENSFCAG00000026640
A2
11454602
11455552
ENSFCAG00000023347
A2
11469229
11470179
ENSFCAG00000028009
A2
11478143
11479132
ENSFCAG00000030787
A2
55532891
55578035
ENSFCAG00000013910
IQSEC1
IQ motif and Sec7 domain 1
A2
58451403
58575137
ENSFCAG00000001776
ALDH1L1
aldehyde dehydrogenase 1 family, member L1
A2
58512851
58512965
ENSFCAG00000020614
5S_rRNA
5S ribosomal RNA
A2
156323262
156324206
ENSFCAG00000025442
A2
156336015
156336959
ENSFCAG00000024190
A2
157059766
157060707
ENSFCAG00000026036
A2
157078181
157079122
ENSFCAG00000025223
A2
162660127
162661174
ENSFCAG00000003990
GIMAP2
GTPase, IMAP family member 2
A2
162671690
162672605
ENSFCAG00000031058
A2
162686216
162686593
ENSFCAG00000027719
A2
162720551
162752217
ENSFCAG00000011443
A3
30261827
30272148
ENSFCAG00000025532
A3
30278131
30288600
ENSFCAG00000030407
A3
30353317
30361064
ENSFCAG00000001879
A3
30372145
30383790
ENSFCAG00000031263
A3
40441218
40441327
ENSFCAG00000024869
5S_rRNA
5S ribosomal RNA
B1
40121
43236
ENSFCAG00000019039
B1
47201
48493
ENSFCAG00000007120
ZNF781
zinc finger protein 781
B1
36295742
36296780
ENSFCAG00000023307
B2
328785
331268
ENSFCAG00000003660
OR12D2
olfactory receptor, family 12, subfamily D, member 2
B2
713302
714237
ENSFCAG00000011606
B2
749421
750359
ENSFCAG00000005124
B2
837074
838335
ENSFCAG00000025316
B2
884452
885396
ENSFCAG00000030837
Dataset S1.11(a). Genes underlying regions of segmental duplications in the
domestic cat genome

B2
906325
906436
ENSFCAG00000027033
5S_rRNA
5S ribosomal RNA
B2
916798
917733
ENSFCAG00000023506
B2
977120
979761
ENSFCAG00000026047
B2
1060434
1061724
ENSFCAG00000028748
B2
1085480
1086424
ENSFCAG00000030186
B2
1104867
1106243
ENSFCAG00000000501
OR2B3
olfactory receptor, family 2, subfamily B, member 3
B2
1129129
1130064
ENSFCAG00000023353
B2
1140538
1144027
ENSFCAG00000028271
B2
1230045
1231165
ENSFCAG00000028202
B2
1243051
1243163
ENSFCAG00000029309
5S_rRNA
5S ribosomal RNA
B2
1257504
1257616
ENSFCAG00000028666
5S_rRNA
5S ribosomal RNA
B2
1277229
1278164
ENSFCAG00000028799
B2
1343658
1344622
ENSFCAG00000025334
B2
1353504
1357463
ENSFCAG00000029693
B2
1459936
1460865
ENSFCAG00000010634
OR2W1
olfactory receptor, family 2, subfamily W, member 1
B2
2299340
2300272
ENSFCAG00000026697
B2
2322927
2323862
ENSFCAG00000029062
B2
2332065
2348095
ENSFCAG00000028781
B2
2364168
2365106
ENSFCAG00000023042
B2
2374024
2374136
ENSFCAG00000030916
5S_rRNA
5S ribosomal RNA
B2
2398409
2399350
ENSFCAG00000027883
B2
2437587
2438525
ENSFCAG00000023744
B2
2529387
2530319
ENSFCAG00000030548
B2
2539008
2539946
ENSFCAG00000025071
B2
32597800
32602576
ENSFCAG00000021900
B2
32667396
32670292
ENSFCAG00000000629
FLA-Z
MHC class I antigen
B2
32703681
32706770
ENSFCAG00000027223
B2
32774101
32776385
ENSFCAG00000015379
B2
32835681
32838540
ENSFCAG00000000877
B2
32870997
32871109
ENSFCAG00000027024
5S_rRNA
5S ribosomal RNA
B2
32907635
32910483
ENSFCAG00000018113
B2
32945158
32948534
ENSFCAG00000027242
FLA-I
MHC class I antigen precursor
B2
33007185
33013570
ENSFCAG00000022105
B3
148227485
148229683
ENSFCAG00000025368
B3
148232277
148232726
ENSFCAG00000028661
B3
148259497
148259934
ENSFCAG00000025324
B3
148322272
148322384
ENSFCAG00000031776
5S_rRNA
5S ribosomal RNA
B4
24696117
24799719
ENSFCAG00000014236
ANKRD26
ankyrin repeat domain 26
B4
24819736
24859130
ENSFCAG00000027161
RAB18
RAB18, member RAS oncogene family
B4
46929808
46931537
ENSFCAG00000013935
B4
46958758
46960567
ENSFCAG00000030370
D1
4486594
4486706
ENSFCAG00000022937
5S_rRNA
5S ribosomal RNA
D1
4776114
4776224
ENSFCAG00000030025
5S_rRNA
5S ribosomal RNA
D1
4803021
4803133
ENSFCAG00000025220
5S_rRNA
5S ribosomal RNA
D1
20649778
20650728
ENSFCAG00000029628
D1
21354029
21355006
ENSFCAG00000002614
D1
21380576
21381508
ENSFCAG00000008131
OR8B12
olfactory receptor, family 8, subfamily B, member 12
D1
64918054
64918998
ENSFCAG00000025048
D1
64938061
64939629
ENSFCAG00000028751
D1
66883484
66884427
ENSFCAG00000024203
D1
66892866
66893789
ENSFCAG00000000727
OR10A3
olfactory receptor, family 10, subfamily A, member 3
D1
66908368
66909313
ENSFCAG00000028608
D1
87753796
88005871
ENSFCAG00000030334
ELP4
elongator acetyltransferase complex subunit 4
D1
88012047
88025138
ENSFCAG00000007094
PAX 6
paired box 6
D1
102240555
102241478
ENSFCAG00000001814
D1
102283570
102284514
ENSFCAG00000024648
D1
102337235
102338164
ENSFCAG00000014680
OR4A47
olfactory receptor, family 4, subfamily A, member 47
D1
103550482
103551426
ENSFCAG00000028369
D1
103568480
103569423
ENSFCAG00000024411
D1
113601303
113688582
ENSFCAG00000004765
PPFIA1
protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 1
D2
129076
129188
ENSFCAG00000029175
5S_rRNA
5S ribosomal RNA
D2
8749213
9075406
ENSFCAG00000029000
D2
8960580
8980244
ENSFCAG00000023704
D2
20153518
20206464
ENSFCAG00000023459
TTC13
tetratricopeptide repeat domain 13
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Dataset S1.11(b). Genes underlying regions of segmental duplications in the
domestic cat genome

D2
22330902
22331016
ENSFCAG00000027550
5S_rRNA
5S ribosomal RNA
D2
22332106
22332224
ENSFCAG00000029290
5S_rRNA
5S ribosomal RNA
D2
22333313
22333421
ENSFCAG00000017601
5S_rRNA
5S ribosomal RNA
D2
22367720
22368642
ENSFCAG00000028109
D2
22379806
22380681
ENSFCAG00000011440
D2
89795938
89805869
ENSFCAG00000013762
CYP2E2
cytochrome P450 2E2
D2
89809103
89814632
ENSFCAG00000031109
ZNF717
zinc finger protein 717
D2
89817222
89822044
ENSFCAG00000013763
SYCE1
synaptonemal complex central element protein 1
D3
80759
80867
ENSFCAG00000021705
5S_rRNA
5S ribosomal RNA
D3
23225438
23225981
ENSFCAG00000025218
D3
23273316
23273795
ENSFCAG00000026724
D3
23297965
23298282
ENSFCAG00000025197
D3
23382135
23382440
ENSFCAG00000029689
D3
23419057
23419488
ENSFCAG00000023616
D3
23509526
23510019
ENSFCAG00000031794
D3
26658713
26658825
ENSFCAG00000027766
5S_rRNA
5S ribosomal RNA
D3
26681356
26709785
ENSFCAG00000006400
PIWIL3
piwi-like RNA-mediated gene silencing 3
D3
28148397
28167337
ENSFCAG00000005999
MED15
mediator complex subunit 15
D3
28167822
28174177
ENSFCAG00000030668
D3
28235497
28244430
ENSFCAG00000006009
P2RX6
purinergic receptor P2X, ligand-gated ion channel, 6
D3
28280102
28284449
ENSFCAG00000022091
TUBA3E
tubulin, alpha 3e
D4
7198
11817
ENSFCAG00000029042
D4
88592476
88595451
ENSFCAG00000023879
D4
88654911
88657790
ENSFCAG00000001496
D4
88692182
88695035
ENSFCAG00000027840
D4
88712762
88715537
ENSFCAG00000031788
D4
95006881
95010017
ENSFCAG00000012216
D4
95011716
95016678
ENSFCAG00000012219
E1
2184
3160
ENSFCAG00000008583
E1
42029674
42032124
ENSFCAG00000030823
E1
56288309
56290286
ENSFCAG00000023215
E1
56322164
56324255
ENSFCAG00000030685
E1
56334152
56334460
ENSFCAG00000001618
E1
56382117
56385015
ENSFCAG00000029475
E2
4520136
4522367
ENSFCAG00000023824
E2
4673182
4688006
ENSFCAG00000028391
E2
4739276
4739981
ENSFCAG00000016263
E2
4893549
4895709
ENSFCAG00000025435
E2
4950706
4951646
ENSFCAG00000030225
E2
4960706
4962448
ENSFCAG00000024112
E2
5330162
5331094
ENSFCAG00000025619
FELCATV1R6
vomeronasal 1 receptor felCatV1R6
E2
5360235
5361671
ENSFCAG00000023132
E2
5412456
5420577
ENSFCAG00000023403
E2
5480972
5529785
ENSFCAG00000023819
E2
5486927
5492030
ENSFCAG00000029493
E2
5537527
5537593
ENSFCAG00000017968
E2
5564448
5571174
ENSFCAG00000031161
E2
5604920
5606596
ENSFCAG00000025806
E2
5641792
5645484
ENSFCAG00000023019
E2
5712974
5714008
ENSFCAG00000028544
E2
5880689
5881638
ENSFCAG00000025070
E2
5887792
5888197
ENSFCAG00000028057
E2
5918068
5919030
ENSFCAG00000022670
FELCATV1R7
vomeronasal 1 receptor felCatV1R7
E2
8497229
8501013
ENSFCAG00000007363
E2
8513256
8529986
ENSFCAG00000022344
FUT2
fucosyltransferase 2 (secretor status included)
E2
8515155
8527136
ENSFCAG00000027085
E2
12316795
12325442
ENSFCAG00000029888
CEACAM21
carcinoembryonic antigen-related cell adhesion molecule 21
E2
13122830
13132919
ENSFCAG00000013094
CYP2S1
cytochrome P450, family 2, subfamily S, polypeptide 1
E3
26876172
26876284
ENSFCAG00000029594
5S_rRNA
5S ribosomal RNA
E3
26994957
27039168
ENSFCAG00000008109
ACSM1
acyl-CoA synthetase medium-chain family member 1
E3
32693517
33115346
ENSFCAG00000010119
SNX29
sorting nexin 29
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Dataset S1.11(c). Genes underlying regions of segmental duplications in the
domestic cat genome

KEGG Pathway
Pathway ID
C
O
E
R
rawP
adjP
Genes
Olfactory transduction
4740
388
7
0.27
25.94
7.7E-09
1.54E-08
OR4A47, OR7C1, OR8B12,
OR10A3, OR12D2, OR2W1, OR2B3
Metabolic pathways
1100
1130
3
0.79
3.82
0.0431
0.0431
FUT2, CYP4F3, ACSM1
Wikipathways Pathway
GPCRs, Class A Rhodopsin-like
WP455
259
3
0.18
16.65
0.0008
0.0014
OR7C1, OR2W1, OR2B3
cytochrome P450
WP43
65
2
0.05
44.23
0.0009
0.0014
CYP2S1, CYP4F3
GO Category (Sub-root)
olfactory receptor activity (molecular function)
GO:0004984
419
7
0.71
9.82
4.64E-06
0.0003
OR4A47, OR7C1, OR8B12,
OR10A3, OR12D2, OR2W1, OR2B3
guanyl nucleotide binding (molecular function)
GO:0019001
392
4
0.67
6
0.0041
0.023
RAB18, TUBA3E, ACSM1,
GIMAP2
USER DATA & PARAMETERS - N = 35 genes submitted, Genes mapped to unique Entrez Gene IDs: 33, Organism: hsapiens, Id Type: gene_symbol, Ref Set: entrezgene,
Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH, Minimum: 2
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category (O), expected number in the category
(E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted by the multiple test adjustment (adjP).
Dataset S1.12. Pathway enrichment results using all genes underlying regions
of segmental duplications in the domestic cat genome (Abyssinian sample)

Dataset S2.1. Coverage statistics per pool.

Dataset S2.2(a). Genes underlying regions of low Hp in the pooled domestic cat
variant dataset following annotation of 100kb windows that fell below four
standard deviations from the mean Hp
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap
With FST
List
A1
8396110
8766675
ENSFCAG00000014322
MTUS2
microtubule associated tumor suppressor candidate 2
A1
8776308
8797912
ENSFCAG00000014326
SLC7A1
solute carrier family 7 (cationic amino acid transporter, y+ system), member 1
A1
40039128
40039239
ENSFCAG00000023540
5S_rRNA
5S ribosomal RNA
A1
52410273
52410385
ENSFCAG00000028097
5S_rRNA
5S ribosomal RNA
A1
52479995
52528867
ENSFCAG00000000561
RBM26
RNA binding motif protein 26
A1
52625952
52688765
ENSFCAG00000025797
NDFIP2
Nedd4 family interacting protein 2
A1
84103052
84104082
ENSFCAG00000015576
A1
84167672
84168631
ENSFCAG00000022722
A1
84208569
84209522
ENSFCAG00000031931
A1
88361081
88362067
ENSFCAG00000026872
OR2G3
olfactory receptor, family 2, subfamily G, member 3
A1
88391241
88392229
ENSFCAG00000008196
A1
88521633
88522592
ENSFCAG00000002236
OR2C3
olfactory receptor, family 2, subfamily C, member 3
A1
88551982
88552917
ENSFCAG00000024148
A1
88616973
88617956
ENSFCAG00000021910
A1
88647235
88648721
ENSFCAG00000008976
A1
88667669
88668640
ENSFCAG00000010456
OR2B11
olfactory receptor, family 2, subfamily B, member 11
A1
88708791
88709744
ENSFCAG00000031962
A1
88723599
88774919
ENSFCAG00000009344
NLRP3
NLR family, pyrin domain containing 3
A1
89064612
89073091
ENSFCAG00000023784
A1
89091044
89092033
ENSFCAG00000006397
RNF187
ring finger protein 187
A1
89124037
89124141
ENSFCAG00000024726
5S_rRNA
5S ribosomal RNA
A1
89136000
89136365
ENSFCAG00000024427
A1
89140926
89141306
ENSFCAG00000032040
HIST3H2BB
histone cluster 3, H2bb
A1
89141619
89142011
ENSFCAG00000024530
HIST3H2A
histone cluster 3, H2a
A1
89163922
89164322
ENSFCAG00000006396
A1
89176315
89184314
ENSFCAG00000029709
TRIM17
tripartite motif containing 17
A1
89187378
89192375
ENSFCAG00000028702
TRIM11
tripartite motif containing 11
A1
89211477
89214157
ENSFCAG00000025004
A1
89215471
89216301
ENSFCAG00000023698
A1
89216810
89218801
ENSFCAG00000022817
A1
89227536
89243984
ENSFCAG00000030432
A1
89246495
89247270
ENSFCAG00000025517
A1
95458053
95465888
ENSFCAG00000031517
A1
95498785
95504740
ENSFCAG00000030457
A1
95525507
95744069
ENSFCAG00000025195
COMMD10
COMM domain containing 10
A1
117462646
117535510
ENSFCAG00000022810
PCDHA1
protocadherin alpha 1
X
A1
117574779
117620293
ENSFCAG00000003685
PCDHAC2
protocadherin alpha subfamily C, 2
A1
117653631
117656087
ENSFCAG00000003687
PCDHB1
protocadherin beta 1
A1
117675941
117678295
ENSFCAG00000001367
PCDHB2
protocadherin beta 2
A1
117694636
117729173
ENSFCAG00000013156
PCDHB4
protocadherin beta 4
X
A1
124586618
124647903
ENSFCAG00000025994
SLC38A9
solute carrier family 38, member 9
A1
124685687
124778148
ENSFCAG00000012560
DDX4
DEAD (Asp-Glu-Ala-Asp) box polypeptide 4
A1
124828501
124867387
ENSFCAG00000010857
IL31RA
interleukin 31 receptor A
A1
124892755
124943980
ENSFCAG00000010859
IL6ST
interleukin 6 signal transducer (gp130, oncostatin M receptor)
A1
125019663
125086857
ENSFCAG00000010860
ANKRD55
ankyrin repeat domain 55
A1
182239426
182624612
ENSFCAG00000008547
EBF1
early B-cell factor 1
A1
182675442
182769870
ENSFCAG00000012160
A1
182768748
182791531
ENSFCAG00000026371
UBLCP1
ubiquitin-like domain containing CTD phosphatase 1
A1
182815541
182825071
ENSFCAG00000015571
IL12B
Interleukin-12 subunit beta
A1
192916759
193132695
ENSFCAG00000014984
GALNT10
UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 10 (GalNAc-T10)
A1
193168465
193168577
ENSFCAG00000026163
5S_rRNA
5S ribosomal RNA
X
A1
193262073
193280914
ENSFCAG00000028091
MFAP3
microfibrillar-associated protein 3
X
A1
193286712
193315803
ENSFCAG00000023708
FAM114A2
family with sequence similarity 114, member A2
X
A1
193479446
193624866
ENSFCAG00000005223
GRIA1
glutamate receptor, ionotropic, AMPA 1
X
A1
219080923
219081031
ENSFCAG00000027389
5S_rRNA
5S ribosomal RNA
A2
110372750
110413021
ENSFCAG00000005018
AHR
aryl hydrocarbon receptor
A2
110810088
110898682
ENSFCAG00000024117
SNX13
sorting nexin 13
A3
24313334
24397487
ENSFCAG00000002305
PIGU
phosphatidylinositol glycan anchor biosynthesis, class U
A3
24398183
24399185
ENSFCAG00000022040
MAP1LC3A
microtubule-associated protein 1 light chain 3 alpha
A3
24418275
24429758
ENSFCAG00000002304
DYNLRB1
dynein, light chain, roadblock-type 1
A3
24443756
24584348
ENSFCAG00000008780
ITCH
itchy E3 ubiquitin protein ligase
A3
24642489
24656544
ENSFCAG00000007301
A3
24671683
24676154
ENSFCAG00000011037
ASIP
Agouti-signaling protein
A3
50153794
50156025
ENSFCAG00000030154
A3
50157809
50158123
ENSFCAG00000027566
A3
50222873
50229392
ENSFCAG00000022966
A3
76497901
76527797
ENSFCAG00000003522
CCDC104
coiled-coil domain containing 104
A3
76529028
76595389
ENSFCAG00000026457
SMEK2
SMEK homolog 2, suppressor of mek1 (Dictyostelium)
A3
76618801
76664057
ENSFCAG00000013236
PNPT1
polyribonucleotide nucleotidyltransferase 1
A3
96863689
96865875
ENSFCAG00000024660

Dataset S2.2(b). Genes underlying regions of low Hp in the pooled domestic cat
variant dataset following annotation of 100kb windows that fell below four
standard deviations from the mean Hp
A3
96889747
96889859
ENSFCAG00000028765
5S_rRNA
5S ribosomal RNA
A3
96900604
96902810
ENSFCAG00000027440
A3
126610231
126619976
ENSFCAG00000028084
A3
126698895
126761424
ENSFCAG00000027520
PUM2
pumilio homolog 2 (Drosophila)
A3
126775239
126796393
ENSFCAG00000005354
SDC1
syndecan 1
A3
141321118
141464325
ENSFCAG00000013984
MYT1L
myelin transcription factor 1-like
B1
44313905
44415983
ENSFCAG00000031578
B1
44440898
44568664
ENSFCAG00000000589
B1
44593908
44639323
ENSFCAG00000030919
B1
44605069
44605181
ENSFCAG00000031785
5S_rRNA
5S ribosomal RNA
B1
44691591
44732046
ENSFCAG00000028945
B1
44746128
44770572
ENSFCAG00000028120
B1
44774622
44784782
ENSFCAG00000023569
B1
44792973
44919764
ENSFCAG00000002595
ADAM9
ADAM metallopeptidase domain 9
B1
44794749
44795624
ENSFCAG00000002701
B1
44920372
44925151
ENSFCAG00000002593
TM2D2
TM2 domain containing 2
B1
44928099
44938386
ENSFCAG00000002591
HTRA4
HtrA serine peptidase 4
B1
44938751
44984295
ENSFCAG00000030276
PLEKHA2
pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 2
B1
45043315
45101607
ENSFCAG00000024992
TACC1
transforming, acidic coiled-coil containing protein 1
B1
104880577
104998796
ENSFCAG00000010364
PDE5A
cGMP-specific 3',5'-cyclic phosphodiesterase
B1
105033096
105036707
ENSFCAG00000026257
FABP2
fatty acid binding protein 2, intestinal
B1
105069890
105121855
ENSFCAG00000014472
USP53
ubiquitin specific peptidase 53
B1
105153960
105193563
ENSFCAG00000003007
MYOZ2
myozenin 2
B1
105252135
105424698
ENSFCAG00000028738
SYNPO2
synaptopodin 2
B1
143593440
143685242
ENSFCAG00000010427
CCDC158
coiled-coil domain containing 158
B1
172072490
172152353
ENSFCAG00000003209
B1
172191715
172262048
ENSFCAG00000025531
UBE2K
ubiquitin-conjugating enzyme E2K
B1
191450950
191588878
ENSFCAG00000029474
LCORL
ligand dependent nuclear receptor corepressor-like
B1
191619013
191665923
ENSFCAG00000030778
NCAPG
non-SMC condensin I complex, subunit G
B2
82062518
82106450
ENSFCAG00000030695
B2
82129137
82129462
ENSFCAG00000022894
B2
82190939
82198755
ENSFCAG00000029256
SRSF12
serine/arginine-rich splicing factor 12
B2
82233859
82249448
ENSFCAG00000014224
PM20D2
peptidase M20 domain containing 2
B2
82263854
82290954
ENSFCAG00000022082
GABRR1
gamma-aminobutyric acid (GABA) A receptor, rho 1
B3
18642298
18719149
ENSFCAG00000007543
CERS3
ceramide synthase 3
B3
33511989
33516370
ENSFCAG00000000344
CYP1A2
Cytochrome P450 1A2
X
B3
33532067
33538470
ENSFCAG00000002016
CYP1A1
Cytochrome P450 1A1
X
B3
33564717
33611587
ENSFCAG00000002014
EDC3
enhancer of mRNA decapping 3 homolog (S. cerevisiae)
X
B3
33611037
33628940
ENSFCAG00000031747
CLK3
CDC-like kinase 3
X
B3
33648267
33702607
ENSFCAG00000002012
ARID3B
AT rich interactive domain 3B (BRIGHT-like)
X
B3
33785369
33799296
ENSFCAG00000027852
UBL7
ubiquitin-like 7 (bone marrow stromal cell-derived)
B3
33820675
33830309
ENSFCAG00000008142
SEMA7A
semaphorin 7A, GPI membrane anchor (John Milton Hagen blood group)
B3
93427038
93427596
ENSFCAG00000023471
B3
111258215
111397325
ENSFCAG00000014176
PPP2R5E
protein phosphatase 2, regulatory subunit B', epsilon isoform
B3
111427724
111428887
ENSFCAG00000025276
WDR89
WD repeat domain 89
B3
111434101
111434478
ENSFCAG00000029391
B3
111477502
111477894
ENSFCAG00000013027
B3
111505184
111540616
ENSFCAG00000031669
SGPP1
sphingosine-1-phosphate phosphatase 1
B3
114616480
114684401
ENSFCAG00000011076
MPP5
membrane protein, palmitoylated 5 (MAGUK p55 subfamily member 5)
B3
114689401
114711272
ENSFCAG00000011078
ATP6V1D
ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D
B3
114715814
114732784
ENSFCAG00000031891
EIF2S1
eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
B3
114733231
114742902
ENSFCAG00000011080
PLEK2
pleckstrin 2
B3
114809050
114809553
ENSFCAG00000031183
TMEM229B
transmembrane protein 229B
B3
114877701
114926189
ENSFCAG00000014084
PLEKHH1
pleckstrin homology domain containing, family H (with MyTH4 domain) member 1
X
B4
39020791
39064360
ENSFCAG00000029824
AKAP3
A kinase (PRKA) anchor protein 3
B4
39067047
39103662
ENSFCAG00000005951
B4
39141172
39189805
ENSFCAG00000005953
GALNT8
UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 8 (GalNAc-T8)
B4
39221313
39222899
ENSFCAG00000002340
KCNA6
potassium voltage-gated channel, shaker-related subfamily, member 6
B4
51667745
51689061
ENSFCAG00000024292
STRAP
serine/threonine kinase receptor associated protein
B4
51747458
51817466
ENSFCAG00000012551
DERA
deoxyribose-phosphate aldolase (putative)
B4
83180790
83186313
ENSFCAG00000010156
B4
83201595
83207215
ENSFCAG00000031316
B4
83212103
83250831
ENSFCAG00000010157
NCKAP1L
NCK-associated protein 1-like
B4
83256882
83284307
ENSFCAG00000010158
PDE1B
phosphodiesterase 1B, calmodulin-dependent
B4
83285929
83289181
ENSFCAG00000010159
PPP1R1A
protein phosphatase 1, regulatory (inhibitor) subunit 1A
B4
85201642
85213246
ENSFCAG00000012017
ANKRD52
ankyrin repeat domain 52
B4
85212877
85212953
ENSFCAG00000021736
B4
85219509
85222879
ENSFCAG00000012018
COQ10A
coenzyme Q10 homolog A (S. cerevisiae)
B4
85223591
85251393
ENSFCAG00000012019
CS
Citrate synthase
B4
85256805
85258874
ENSFCAG00000012020
B4
85261031
85272858
ENSFCAG00000012021
PAN 2
PAN2 poly(A) specific ribonuclease subunit homolog (S. cerevisiae)
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap
With FST
List

Dataset S2.2(c). Genes underlying regions of low Hp in the pooled domestic cat
variant dataset following annotation of 100kb windows that fell below four
standard deviations from the mean Hp
B4
85277282
85279111
ENSFCAG00000012022
IL23A
interleukin 23, alpha subunit p19
B4
85281059
85298979
ENSFCAG00000012023
STAT2
signal transducer and activator of transcription 2, 113kDa
B4
85300402
85302055
ENSFCAG00000028837
APOF
apolipoprotein F
B4
85313463
85330693
ENSFCAG00000012024
TIMELESS
timeless circadian clock
B4
85345392
85348942
ENSFCAG00000012025
MIP
major intrinsic protein of lens fiber
B4
85359827
85362487
ENSFCAG00000023005
SPRYD4
SPRY domain containing 4
B4
85360205
85376232
ENSFCAG00000012027
GLS2
glutaminase 2 (liver, mitochondrial)
B4
85400194
85463992
ENSFCAG00000012028
RBMS2
RNA binding motif, single stranded interacting protein 2
C1
10640571
10657545
ENSFCAG00000011590
FBLIM1
filamin binding LIM protein 1
C1
10732129
10795582
ENSFCAG00000010165
SPEN
spen homolog, transcriptional regulator (Drosophila)
C1
10796361
10827960
ENSFCAG00000023421
ZBTB17
zinc finger and BTB domain containing 17
C1
10837025
10839250
ENSFCAG00000010166
C1orf64
chromosome 1 open reading frame 64
C1
10848258
10852249
ENSFCAG00000026415
HSPB7
heat shock 27kDa protein family, member 7 (cardiovascular)
C1
58101938
58102050
ENSFCAG00000031207
5S_rRNA
5S ribosomal RNA
C1
78698661
78717765
ENSFCAG00000031703
DNTTIP2
deoxynucleotidyltransferase, terminal, interacting protein 2
C1
78722799
78738417
ENSFCAG00000026377
GCLM
glutamate-cysteine ligase, modifier subunit
C1
78772870
78906672
ENSFCAG00000015512
ABCA4
ATP-binding cassette, sub-family A (ABC1), member 4
C1
84943030
84960266
ENSFCAG00000011031
VCAM1
vascular cell adhesion molecule 1
C1
85015454
85015558
ENSFCAG00000025299
5S_rRNA
5S ribosomal RNA
C1
85064668
85071066
ENSFCAG00000023298
EXTL2
exostoses (multiple)-like 2
C1
85087065
85167096
ENSFCAG00000011033
SLC30A7
solute carrier family 30 (zinc transporter), member 7
C1
85133519
85134071
ENSFCAG00000028505
C1
85186588
85225405
ENSFCAG00000022542
DPH5
DPH5 homolog (S. cerevisiae)
C1
153704054
153753962
ENSFCAG00000004699
GRB14
growth factor receptor-bound protein 14
C1
154302722
154384425
ENSFCAG00000024761
SCN3A
sodium channel, voltage-gated, type III, alpha subunit
C1
181824781
181826420
ENSFCAG00000010136
C1
181987901
182031850
ENSFCAG00000029020
SLC39A10
solute carrier family 39 (zinc transporter), member 10
C2
77632001
77703504
ENSFCAG00000000693
ATP13A5
ATPase type 13A5
C2
77706977
77717650
ENSFCAG00000000692
C2
78412932
78673284
ENSFCAG00000025224
FGF12
fibroblast growth factor 12
C2
108304270
108463279
ENSFCAG00000012834
PLCH1
phospholipase C, eta 1
C2
108510488
108510600
ENSFCAG00000031412
5S_rRNA
5S ribosomal RNA
C2
128014862
128022609
ENSFCAG00000009596
RAB6B
RAB6B, member RAS oncogene family
C2
128027632
128059443
ENSFCAG00000026858
SRPRB
signal recognition particle receptor, B subunit
C2
128061749
128090487
ENSFCAG00000009592
TF
transferrin
C2
128112530
128155615
ENSFCAG00000027859
C2
128189988
128251128
ENSFCAG00000005146
TOPBP1
topoisomerase (DNA) II binding protein 1
D1
1607316
1636408
ENSFCAG00000029835
DCUN1D5
DCN1, defective in cullin neddylation 1, domain containing 5 (S. cerevisiae)
D1
1651507
1992762
ENSFCAG00000028573
DYNC2H1
dynein, cytoplasmic 2, heavy chain 1
D1
30227928
30233580
ENSFCAG00000011024
SPATA19
spermatogenesis associated 19
D1
30287365
30324514
ENSFCAG00000007138
IGSF9B
immunoglobulin superfamily, member 9B
D1
53604863
53604975
ENSFCAG00000030335
5S_rRNA
5S ribosomal RNA
D1
107809557
107915426
ENSFCAG00000008866
UBXN1
UBX domain protein 1 [Source:HGNC Symbol;Acc:18402]
D1
107850747
107857696
ENSFCAG00000008861
MTA2
metastasis associated 1 family, member 2
D1
107858491
107867300
ENSFCAG00000008862
EML3
echinoderm microtubule associated protein like 3
D1
107868913
107870543
ENSFCAG00000008863
ROM1
retinal outer segment membrane protein 1
D1
107870916
107875681
ENSFCAG00000008864
B3GAT3
beta-1,3-glucuronyltransferase 3 (glucuronosyltransferase I)
D1
107876904
107892987
ENSFCAG00000008865
GANAB
glucosidase, alpha; neutral AB
D1
107889470
107890314
ENSFCAG00000030933
D1
107893127
107897937
ENSFCAG00000022488
INTS5
integrator complex subunit 5
D1
107901491
107905417
ENSFCAG00000025454
D1
107906121
107907032
ENSFCAG00000019062
METTL12
methyltransferase like 12
D1
107910273
107910654
ENSFCAG00000026508
C11orf83
chromosome 11 open reading frame 83
D1
107918401
107919123
ENSFCAG00000008867
LRRN4CL
LRRN4 C-terminal like
D1
107920655
107930057
ENSFCAG00000018428
BSCL2
Berardinelli-Seip congenital lipodystrophy 2 (seipin)
D1
107931091
107931596
ENSFCAG00000006326
D1
107937649
107947789
ENSFCAG00000014766
D1
107948981
107954599
ENSFCAG00000014768
TTC9C
tetratricopeptide repeat domain 9C
D1
107961224
107964011
ENSFCAG00000027690
ZBTB3
zinc finger and BTB domain containing 3
D1
107973264
107976548
ENSFCAG00000026072
POLR2G
polymerase (RNA) II (DNA directed) polypeptide G
D1
107984157
107992940
ENSFCAG00000022346
TAF6L
TAF6-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associated factor, 65kDa
D1
107993688
107994689
ENSFCAG00000014773
TMEM179B
transmembrane protein 179B
D1
107995077
107996089
ENSFCAG00000025098
TMEM223
transmembrane protein 223
D1
107996609
108006783
ENSFCAG00000014774
NXF1
nuclear RNA export factor 1
D1
108008793
108027809
ENSFCAG00000014778
STX5
syntaxin 5
D1
108029559
108035227
ENSFCAG00000014780
WDR74
WD repeat domain 74
D1
108066532
108073223
ENSFCAG00000014781
SLC3A2
solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2
D1
108091101
108092483
ENSFCAG00000000336
CHRM1
cholinergic receptor, muscarinic 1
D1
111390904
111406979
ENSFCAG00000007404
SYT12
synaptotagmin XII
D1
111418646
111423350
ENSFCAG00000007405
RHOD
ras homolog family member D
D1
111493966
111569206
ENSFCAG00000003383
KDM2A
lysine (K)-specific demethylase 2A
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap
With FST
List

Dataset S2.2(d). Genes underlying regions of low Hp in the pooled domestic cat
variant dataset following annotation of 100kb windows that fell below four
standard deviations from the mean Hp
D1
111590001
111597609
ENSFCAG00000003386
ADRBK1
adrenergic, beta, receptor kinase 1
D1
111598900
111611310
ENSFCAG00000003388
ANKRD13D
ankyrin repeat domain 13 family, member D
D1
111612360
111620131
ENSFCAG00000003389
SSH3
slingshot homolog 3 (Drosophila)
D1
111642857
111644862
ENSFCAG00000026317
POLD4
polymerase (DNA-directed), delta 4, accessory subunit
D2
129076
129188
ENSFCAG00000029175
5S_rRNA
5S ribosomal RNA
D2
57260928
57261537
ENSFCAG00000031023
D2
57304321
57346173
ENSFCAG00000014012
ENTPD1
ectonucleoside triphosphate diphosphohydrolase 1
D2
57377604
57453891
ENSFCAG00000024547
D3
16753418
16765475
ENSFCAG00000023496
UNC119B
unc-119 homolog B (C. elegans)
D3
16767557
16779781
ENSFCAG00000002402
ACADS
acyl-CoA dehydrogenase, C-2 to C-3 short chain
D3
16818395
16846475
ENSFCAG00000030187
SPPL3
signal peptide peptidase like 3
D3
27486649
27511914
ENSFCAG00000004294
UFD1L
ubiquitin fusion degradation 1 like (yeast)
D3
27514585
27517737
ENSFCAG00000025374
C22orf39
chromosome 22 open reading frame 39
D3
27522219
27526181
ENSFCAG00000002752
MRPL40
mitochondrial ribosomal protein L40
D3
27545550
27619849
ENSFCAG00000002750
HIRA
HIR histone cell cycle regulation defective homolog A (S. cerevisiae)
D3
27661078
27763200
ENSFCAG00000002747
CLTCL1
clathrin, heavy chain-like 1
D3
28412397
28523536
ENSFCAG00000006001
PI4KA
phosphatidylinositol 4-kinase, catalytic, alpha
D3
28460397
28469039
ENSFCAG00000006002
SERPIND1
serpin peptidase inhibitor, clade D (heparin cofactor), member 1
D3
28532228
28532992
ENSFCAG00000003742
D3
28549103
28552706
ENSFCAG00000023903
HIC2
hypermethylated in cancer 2
D3
28587145
28591887
ENSFCAG00000008005
D3
28601226
28653670
ENSFCAG00000008008
UBE2L3
ubiquitin-conjugating enzyme E2L 3
D3
28659840
28661374
ENSFCAG00000008011
YDJC
YdjC homolog (bacterial)
D3
28663783
28666362
ENSFCAG00000027678
CCDC116
coiled-coil domain containing 116
D3
28672570
28674479
ENSFCAG00000008014
SDF2L1
stromal cell-derived factor 2-like 1
D3
28677737
28677830
ENSFCAG00000024408
D3
28678081
28678140
ENSFCAG00000029099
D3
28680749
28690369
ENSFCAG00000031033
D3
28692128
28720327
ENSFCAG00000002622
PPIL2
peptidylprolyl isomerase (cyclophilin)-like 2
D3
28724636
28743087
ENSFCAG00000028941
YPEL1
yippee-like 1 (Drosophila)
D3
28767507
28877605
ENSFCAG00000023435
MAPK1
mitogen-activated protein kinase 1
D3
28905826
28929444
ENSFCAG00000002630
PPM1F
protein phosphatase, Mg2+/Mn2+ dependent, 1F
D3
28941162
28961110
ENSFCAG00000002631
TOP3B
topoisomerase (DNA) III beta
D3
29050629
29085036
ENSFCAG00000011848
D3
29119195
29120502
ENSFCAG00000004058
VPREB3
pre-B lymphocyte 3
D3
29124112
29125589
ENSFCAG00000004065
C22orf15
chromosome 22 open reading frame 15
D3
29126680
29128333
ENSFCAG00000004059
CHCHD10
coiled-coil-helix-coiled-coil-helix domain containing 10
D3
29130819
29140423
ENSFCAG00000015309
MMP11
matrix metallopeptidase 11 (stromelysin 3)
D3
29141586
29176322
ENSFCAG00000004068
SMARCB1
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1
D3
29178943
29181128
ENSFCAG00000004069
DERL3
derlin 3
D3
29194518
29214625
ENSFCAG00000004070
D3
29230481
29231130
ENSFCAG00000004071
MIF
macrophage migration inhibitory factor (glycosylation-inhibiting factor)
D3
32440361
32440473
ENSFCAG00000028017
5S_rRNA
5S ribosomal RNA
D3
73217674
73955407
ENSFCAG00000012953
DCC
deleted in colorectal carcinoma
X
E1
29838089
29850820
ENSFCAG00000018819
PRR11
proline rich 11
E1
29867217
29867300
ENSFCAG00000022665
E1
29878598
29878667
ENSFCAG00000023049
E1
29884263
29908906
ENSFCAG00000022802
E1
29914732
30045189
ENSFCAG00000013333
TRIM37
tripartite motif containing 37
E2
45291420
45336043
ENSFCAG00000003492
CTCF
CCCTC-binding factor (zinc finger protein)
E2
45340148
45352135
ENSFCAG00000009279
RLTPR
RGD motif, leucine rich repeats, tropomodulin domain and proline-rich containing
E2
45344436
45344645
ENSFCAG00000023723
E2
45352266
45355166
ENSFCAG00000009280
ACD
adrenocortical dysplasia homolog (mouse)
E2
45355872
45357527
ENSFCAG00000009281
PARD6A
par-6 partitioning defective 6 homolog alpha (C. elegans)
E2
45358052
45361200
ENSFCAG00000009282
ENKD1
enkurin domain containing 1
E2
45361603
45363331
ENSFCAG00000026033
C16orf86
chromosome 16 open reading frame 86
E2
45369230
45375475
ENSFCAG00000003493
GFOD2
glucose-fructose oxidoreductase domain containing 2
E2
45408032
45469729
ENSFCAG00000003494
RANBP10
ran-binding protein 10
E2
45440127
45440219
ENSFCAG00000029801
E2
45468767
45482371
ENSFCAG00000012848
TSNAXIP1
translin-associated factor X interacting protein 1
E2
45482659
45488605
ENSFCAG00000012849
CENPT
centromere protein T
E2
45492005
45492928
ENSFCAG00000012850
THAP11
THAP domain containing 11
F2
78455289
78455684
ENSFCAG00000023697
F2
78470381
78470478
ENSFCAG00000031046
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap
With FST
List

Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated Gene
Name
Description
Overlap With Low
Domestic Hp
A1
11398212
11455078
ENSFCAG00000025587
BRCA2
breast cancer type 2 susceptibility protein homolog
A1
11458331
11465570
ENSFCAG00000024257
N4BP2L1
NEDD4 binding protein 2-like 1
A1
11495916
11500421
ENSFCAG00000022569
N4BP2L2
NEDD4 binding protein 2-like 2
A1
11500635
11566192
ENSFCAG00000027199
A1
117311206
117312333
ENSFCAG00000001278
CD14
CD14 molecule
A1
117316550
117322265
ENSFCAG00000001280
TMCO6
transmembrane and coiled-coil domains 6
A1
117322928
117325000
ENSFCAG00000001282
NDUFA2
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa
A1
117325316
117335480
ENSFCAG00000001279
IK
IK cytokine, down-regulator of HLA II
A1
117339751
117346166
ENSFCAG00000031277
WDR55
WD repeat domain 55
A1
117344253
117346522
ENSFCAG00000001285
DND1
dead end homolog 1 (zebrafish)
A1
117347249
117360519
ENSFCAG00000001286
HARS
histidyl-tRNA synthetase
A1
117360312
117367965
ENSFCAG00000001288
HARS2
histidyl-tRNA synthetase 2, mitochondrial
A1
117368560
117373405
ENSFCAG00000001289
ZMAT2
zinc finger, matrin-type 2
A1
117462646
117535510
ENSFCAG00000022810
PCDHA1
protocadherin alpha 1
X
A1
117694636
117729173
ENSFCAG00000013156
PCDHB4
protocadherin beta 4
X
A1
117745827
117769414
ENSFCAG00000003467
PCDHB14
protocadherin beta 14
A1
117799797
117801198
ENSFCAG00000029398
SLC25A2
solute carrier family 25 (mitochondrial carrier; ornithine transporter) member 2
A1
117809591
117810640
ENSFCAG00000025624
TAF 7
TAF7 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 55kDa
A1
117822381
117986226
ENSFCAG00000027095
PCDHGC4
protocadherin gamma subfamily C, 4
A1
193168465
193168577
ENSFCAG00000026163
5S_rRNA
5S ribosomal RNA
X
A1
193262073
193280914
ENSFCAG00000028091
MFAP3
microfibrillar-associated protein 3
X
A1
193286712
193315803
ENSFCAG00000023708
FAM114A2
family with sequence similarity 114, member A2
X
A1
193353906
193354042
ENSFCAG00000030338
A1
193479446
193624866
ENSFCAG00000005223
GRIA1
glutamate receptor, ionotropic, AMPA 1
X
A2
18272574
18306642
ENSFCAG00000031387
BSN
bassoon presynaptic cytomatrix protein
A2
18315503
18324298
ENSFCAG00000028315
APEH
N-acylaminoacyl-peptide hydrolase
A2
18324835
18329543
ENSFCAG00000025772
MST1
macrophage stimulating 1 (hepatocyte growth factor-like)
A2
18331960
18361039
ENSFCAG00000022451
RNF123
ring finger protein 123
A2
18358000
18359547
ENSFCAG00000010675
AMIGO3
adhesion molecule with Ig-like domain 3
A2
18361478
18363484
ENSFCAG00000010676
GMPPB
GDP-mannose pyrophosphorylase B
A2
18367013
18386714
ENSFCAG00000010677
IP6K1
inositol hexakisphosphate kinase 1
A2
18422363
18430166
ENSFCAG00000029853
CDHR4
cadherin-related family member 4
A2
18433891
18435481
ENSFCAG00000010679
FAM212A
family with sequence similarity 212, member A
A2
18435671
18444581
ENSFCAG00000010680
UBA7
ubiquitin-like modifier activating enzyme 7
A2
18450943
18472637
ENSFCAG00000010682
TRAIP
TRAF interacting protein
A2
18475364
18478459
ENSFCAG00000010683
CAMKV
CaM kinase-like vesicle-associated
A2
18489446
18493192
ENSFCAG00000024955
A2
20299485
20562418
ENSFCAG00000015704
POC1A
POC1 centriolar protein homolog A (Chlamydomonas)
A2
20524053
20596054
ENSFCAG00000015710
DNAH1
dynein, axonemal, heavy chain 1
A2
20596545
20605161
ENSFCAG00000015711
BAP1
BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)
A2
20605964
20617985
ENSFCAG00000015712
PHF7
PHD finger protein 7
A2
20628755
20638133
ENSFCAG00000015713
SEMA3G
sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3G
A2
20643522
20646338
ENSFCAG00000015714
TNNC1
troponin C type 1 (slow)
A2
20648138
20682140
ENSFCAG00000015715
NISCH
nischarin
A2
20684301
20710994
ENSFCAG00000015716
STAB1
stabilin 1
A2
56358682
56359374
ENSFCAG00000001739
DNAJB8
DnaJ (Hsp40) homolog, subfamily B, member 8
A2
56408518
56572045
ENSFCAG00000006153
EEFSEC
eukaryotic elongation factor, selenocysteine-tRNA-specific
B1
104314018
104319723
ENSFCAG00000023700
B3
562402
612682
ENSFCAG00000010511
TBC1D2B
TBC1 domain family, member 2B
B3
614460
645400
ENSFCAG00000019139
ADAMTS7
ADAM metallopeptidase with thrombospondin type 1 motif, 7
B3
692868
709793
ENSFCAG00000012197
B3
724131
733861
ENSFCAG00000012198
CTSH
cathepsin H
B3
752155
849199
ENSFCAG00000012199
RASGRF1
Ras protein-specific guanine nucleotide-releasing factor 1
B3
23976933
24067525
ENSFCAG00000027111
UBE3A
ubiquitin protein ligase E3A
B3
26496373
26600819
ENSFCAG00000023805
GABRG3
gamma-aminobutyric acid (GABA) A receptor, gamma 3
Dataset S2.3(a). Genes underlying regions of high FST in the pooled domestic
cat variant dataset relative to the pooled wildcat variant dataset

B3
31880462
31899698
ENSFCAG00000022033
RCN2
reticulocalbin 2, EF-hand calcium binding domain
B3
31953456
31981469
ENSFCAG00000010953
PSTPIP1
proline-serine-threonine phosphatase interacting protein 1
B3
31986675
32018232
ENSFCAG00000025746
TSPAN3
tetraspanin 3
B3
32061239
32135509
ENSFCAG00000026195
B3
32120379
32121889
ENSFCAG00000031049
B3
32401108
32428309
ENSFCAG00000022539
HMG20A
high mobility group 20A
B3
32540693
32558379
ENSFCAG00000013212
LINGO1
leucine rich repeat and Ig domain containing 1
B3
33511989
33516370
ENSFCAG00000000344
CYP1A2
Cytochrome P450 1A2
X
B3
33532067
33538470
ENSFCAG00000002016
CYP1A1
Cytochrome P450 1A1
X
B3
33564717
33611587
ENSFCAG00000002014
EDC3
enhancer of mRNA decapping 3 homolog (S. cerevisiae)
X
B3
33611037
33628940
ENSFCAG00000031747
CLK3
CDC-like kinase 3
X
B3
33648267
33702607
ENSFCAG00000002012
ARID3B
AT rich interactive domain 3B (BRIGHT-like)
X
B3
113916112
114542162
ENSFCAG00000013487
GPHN
gephyrin
B3
114877701
114926189
ENSFCAG00000014084
PLEKHH1
pleckstrin homology domain containing, family H (with MyTH4 domain) member 1
X
B3
114924265
114931845
ENSFCAG00000014087
PIGH
phosphatidylinositol glycan anchor biosynthesis, class H
B3
114944868
114977046
ENSFCAG00000014088
ARG2
arginase, type II
B3
114976632
115008847
ENSFCAG00000014090
B3
114997195
114997263
ENSFCAG00000021393
B3
115012454
115028806
ENSFCAG00000014091
RDH11
retinol dehydrogenase 11 (all-trans/9-cis/11-cis)
B3
115040768
115049236
ENSFCAG00000014092
RDH12
retinol dehydrogenase 12 (all-trans/9-cis/11-cis)
B3
115064179
115135168
ENSFCAG00000007653
ZFYVE26
zinc finger, FYVE domain containing 26
B3
115157242
115190375
ENSFCAG00000007657
RAD51B
RAD51 homolog B (S. cerevisiae)
B3
126320314
126713029
ENSFCAG00000007824
CEP128
centrosomal protein 128kDa
B3
126725185
126884461
ENSFCAG00000011083
TSHR
thyrotropin receptor precursor
B4
143787880
143800787
ENSFCAG00000011914
PLXNB2
plexin B2
B4
143815714
143824099
ENSFCAG00000011915
DENND6B
DENN/MADD domain containing 6B
B4
143870997
143920737
ENSFCAG00000004431
PPP6R2
protein phosphatase 6, regulatory subunit 2
B4
143923211
143944516
ENSFCAG00000004434
SBF1
SET binding factor 1
B4
143955788
143956879
ENSFCAG00000022957
ADM2
adrenomedullin 2
B4
143960792
143962760
ENSFCAG00000013030
MIOX
myo-inositol oxygenase
B4
143974923
143979512
ENSFCAG00000013032
LMF2
lipase maturation factor 2
B4
143979545
143979666
ENSFCAG00000028233
B4
143979850
143995006
ENSFCAG00000013034
NCAPH2
non-SMC condensin II complex, subunit H2
B4
143992569
143993369
ENSFCAG00000013035
SCO2
SCO2 cytochrome c oxidase assembly protein
B4
143998592
144000511
ENSFCAG00000021933
ODF3B
outer dense fiber of sperm tails 3B
C1
81116342
81201784
ENSFCAG00000027655
PTBP2
polypyrimidine tract binding protein 2
C1
87218356
87218468
ENSFCAG00000028148
5S_rRNA
5S ribosomal RNA
C1
87333358
87358352
ENSFCAG00000024312
RNPC3
RNA-binding region (RNP1, RRM) containing 3
C1
102252296
102252706
ENSFCAG00000029741
HIST2H3D
histone cluster 2, H3d
C1
102253768
102254160
ENSFCAG00000026932
C1
102254475
102254892
ENSFCAG00000027797
C1
102288465
102288845
ENSFCAG00000023970
HIST2H2BE
histone cluster 2, H2be
C1
102289173
102289562
ENSFCAG00000024806
HIST2H2AC
histone cluster 2, H2ac
C1
102289719
102290111
ENSFCAG00000028667
HIST2H2AB
histone cluster 2, H2ab
C1
102300828
102301241
ENSFCAG00000010103
BOLA1
bolA homolog 1 (E. coli)
C1
102306044
102313944
ENSFCAG00000010104
SV2A
synaptic vesicle glycoprotein 2A
C1
102328326
102332748
ENSFCAG00000010106
SF3B4
splicing factor 3b, subunit 4, 49kDa
C1
102334404
102341438
ENSFCAG00000010108
MTMR11
myotubularin related protein 11
C1
102347722
102369563
ENSFCAG00000010110
OTUD7B
OTU domain containing 7B
C1
103510046
103513819
ENSFCAG00000005568
RFX5
regulatory factor X, 5 (influences HLA class II expression)
C1
103523531
103532221
ENSFCAG00000001859
SELENBP1
selenium binding protein 1
C1
103572933
103576251
ENSFCAG00000001861
PSMB4
proteasome (prosome, macropain) subunit, beta type, 4
C1
103579750
103629870
ENSFCAG00000001864
POGZ
pogo transposable element with ZNF domain
C1
103669485
103693186
ENSFCAG00000004072
CGN
cingulin
C1
103694358
103735432
ENSFCAG00000004073
TUFT1
tuftelin 1
C1
104304676
104409375
ENSFCAG00000022223
FLG2
filaggrin family member 2
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated Gene
Name
Description
Overlap With Low
Domestic Hp
Dataset S2.3(b). Genes underlying regions of high FST in the pooled domestic
cat variant dataset relative to the pooled wildcat variant dataset

C1
104308093
104310222
ENSFCAG00000025915
HRNR
hornerin
C1
104341706
104342582
ENSFCAG00000028908
FLG
filaggrin
C1
104478129
104480640
ENSFCAG00000030196
CRNN
cornulin
C1
142020467
142037136
ENSFCAG00000027956
TNFAIP6
tumor necrosis factor, alpha-induced protein 6
C1
142068033
142135438
ENSFCAG00000029742
RIF1
RAP1 interacting factor homolog (yeast)
C1
142149853
142362875
ENSFCAG00000006778
NEB
nebulin
D1
87552960
87615211
ENSFCAG00000015003
DCDC1
doublecortin domain containing 1
D3
73217674
73955407
ENSFCAG00000012953
DCC
deleted in colorectal carcinoma
X
E1
2012450
2018802
ENSFCAG00000001360
ASGR1
asialoglycoprotein receptor 1
E1
2062948
2084818
ENSFCAG00000002824
DLG4
discs, large homolog 4 (Drosophila)
E1
2071965
2654649
ENSFCAG00000009629
CHD3
chromodomain helicase DNA binding protein 3
E1
2085784
2091265
ENSFCAG00000002826
ACADVL
acyl-CoA dehydrogenase, very long chain
E1
2089360
2089473
ENSFCAG00000020094
E1
2092041
2099011
ENSFCAG00000024333
DVL2
dishevelled, dsh homolog 2 (Drosophila)
E1
2099343
2103630
ENSFCAG00000025727
PHF23
PHD finger protein 23
E1
2105175
2106741
ENSFCAG00000030191
GABARAP
GABA(A) receptor-associated protein
E1
2108629
2114091
ENSFCAG00000018399
CTDNEP1
CTD nuclear envelope phosphatase 1
E1
2115255
2120631
ENSFCAG00000002827
ELP5
elongator acetyltransferase complex subunit 5
E1
2121374
2122689
ENSFCAG00000031173
E1
2133863
2138934
ENSFCAG00000003061
SLC2A4
solute carrier family 2 (facilitated glucose transporter), member 4
E1
2140924
2144812
ENSFCAG00000018097
YBX2
Y box binding protein 2
E1
2160740
2165161
ENSFCAG00000010886
E1
2166294
2168525
ENSFCAG00000030260
E1
2169030
2180923
ENSFCAG00000010887
E1
2182103
2185125
ENSFCAG00000030827
E1
2186123
2197946
ENSFCAG00000010890
ACAP1
ArfGAP with coiled-coil, ankyrin repeat and PH domains 1
E1
2202287
2203655
ENSFCAG00000010892
TMEM95
transmembrane protein 95
E1
2213358
2218182
ENSFCAG00000010893
TNK1
tyrosine kinase, non-receptor, 1
E1
2219417
2222502
ENSFCAG00000010894
PLSCR3
phospholipid scramblase 3
E1
2239238
2240164
ENSFCAG00000029899
E1
2245191
2253571
ENSFCAG00000031923
NLGN2
neuroligin 2
E3
19523974
19531163
ENSFCAG00000006398
TRIM72
tripartite motif containing 72
E3
19542074
19543165
ENSFCAG00000002608
PYCARD
PYD and CARD domain containing
E3
19551867
19563123
ENSFCAG00000027928
FUS
fused in sarcoma
E3
19590723
19599388
ENSFCAG00000002607
PRSS36
protease, serine, 36
E3
19602108
19605310
ENSFCAG00000002606
PRSS8
protease, serine, 8
E3
19606046
19617514
ENSFCAG00000002605
KAT8
K(lysine) acetyltransferase 8
E3
19619822
19623515
ENSFCAG00000002604
BCKDK
branched chain ketoacid dehydrogenase kinase
E3
19631084
19634172
ENSFCAG00000029684
E3
19635291
19640292
ENSFCAG00000002602
PRSS53
protease, serine, 53
E3
19638036
19647917
ENSFCAG00000021918
ZNF646
zinc finger protein 646
E3
19656066
19658480
ENSFCAG00000008954
ZNF668
zinc finger protein 668
E3
19670742
19679273
ENSFCAG00000030459
STX4
syntaxin 4
E3
19700268
19707021
ENSFCAG00000002598
STX1B
syntaxin 1B
E3
19710473
19714090
ENSFCAG00000002594
HSD3B7
hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7
E3
19715271
19736956
ENSFCAG00000002588
SETD1A
SET domain containing 1A
E3
19740874
19745210
ENSFCAG00000023192
ORAI3
ORAI calcium release-activated calcium modulator 3
E3
19747142
19766168
ENSFCAG00000002585
FBXL19
F-box and leucine-rich repeat protein 19
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated Gene
Name
Description
Overlap With Low
Domestic Hp
Dataset S2.3(c). Genes underlying regions of high FST in the pooled domestic
cat variant dataset relative to the pooled wildcat variant dataset

Genes Underlying Putative Regions of Selection in the Domestic Cat
Region
Chr:Pos
Gene ID
Gene Name
Description
Domestic
Z(Hp)
Z(FST)
Wildcat
Z(Hp)
1
A1:117462646-117535510
ENSFCAG00000022810
PCDHA1
protocadherin alpha 1
-4.6 to!
-4.2
4.0 to !
4.5
-2.6 to!
-1.5
A1:117694636-117729173
ENSFCAG00000013156
PCDHB4
protocadherin beta 4
2
A1:193168465-193168577
ENSFCAG00000026163
5S ribosomal RNA
-4.4 to!
-4.1
4.5 to !
5.2
0 to!
0.6
A1:193262073-193280914
ENSFCAG00000028091
MFAP3
microfibrillar-associated protein 3
A1:193286712-193315803
ENSFCAG00000023708
FAM114A2
family with sequence similarity 114,
member A2
A1:193479446-193624866
ENSFCAG00000005223
GRIA1
glutamate receptor, ionotropic, AMPA 1
3
B3: 33511989-33516370
ENSFCAG00000000344
CYP1A2
cytochrome P450 1A2
-8.9 to!
-5.6
4.7 to !
5.2
0.7 to!
0.8
B3:33532067-33538470
ENSFCAG00000002016
CYP1A1
cytochrome P450 1A1
B3:33564717-33611587
ENSFCAG00000002014
EDC3
enhancer of mRNA decapping 3 homolog
B3:33611037-33628940
ENSFCAG00000031747
CLK3
CDC-like kinase 3
B3:33648267-33702607
ENSFCAG00000002012
ARID3B
AT rich interactive domain 3B (BRIGHT-
like)
4
B3: 114877701-114926189
ENSFCAG00000014084
PLEKHH1
pleckstrin homology domain containing,
family H (with MyTH4 domain) member 1
-4.6
4.1
0.3
5
D3: 73217674-73955407
ENSFCAG00000012953
DCC
deleted in colorectal carcinoma
-4.3
4.2
-0.8
Table 2. Summary of genes underlying regions of elevated FST and low Hp in the pooled domestic cats.
Dataset S2.4. Summary of genes underlying regions of elevated FST and low Hp
in the pooled domestic cats.

KEGG Pathway
Pathway ID
C
O
E
R
rawP
adjP
Genes
Retinol metabolism
830
64
4
0.20
20.12
4.90E-05
0.0009
RDH12, CYP1A1, CYP1A2, RDH11
Systemic lupus erythematosus
5322
136
4
0.42
9.47
0.0009
0.0081
HIST2H3D, HIST2H2BE, HIST2H2AC,
HIST2H2AB
Metabolic pathways
1100
1130
10
3.51
2.85
0.0029
0.0153
ARG2, CYP1A1, NDUFA2, CYP1A2,
PIGH, GMPPB, RDH12, ACADVL,
HSD3B7, RDH11
Homologous recombination
3440
28
2
0.09
22.99
0.0034
0.0153
BRCA2, RAD51B
Tryptophan metabolism
380
42
2
0.13
15.33
0.0076
0.0198
CYP1A1, CYP1A2
SNARE interactions in
vesicular transport
4130
36
2
0.11
17.88
0.0056
0.0198
STX4, STX1B
Axon guidance
4360
129
3
0.40
7.48
0.0077
0.0198
SEMA3G, DCC, PLXNB2
NOD-like receptor signaling
pathway
4621
58
2
0.18
11.10
0.0141
0.0317
PSTPIP1, PYCARD
Aminoacyl-tRNA biosynthesis
970
63
2
0.20
10.22
0.0165
0.0330
HARS2, HARS
Metabolism of xenobiotics by
cytochrome P450
980
71
2
0.22
9.07
0.0207
0.0339
CYP1A1, CYP1A2
Huntington's disease
5016
183
3
0.57
5.28
0.0196
0.0339
DLG4, NDUFA2, DNAH1
Wikipathway
AhR pathway
WP2100
39
3
0.12
24.76
0.0002
0.0034
CYP1A1, FLG, CYP1A2
Tryptophan metabolism
WP465
69
3
0.21
13.99
0.0013
0.0055
CYP1A1, UBE3A, CYP1A2
Fatty Acid Omega Oxidation
WP206
15
2
0.05
42.91
0.0010
0.0055
CYP1A1, CYP1A2
mRNA processing
WP411
132
4
0.41
9.75
0.0008
0.0055
FUS, SF3B4, PTBP2, CLK3
Striated Muscle Contraction
WP383
38
2
0.12
16.94
0.0063
0.016
TNNC1, NEB
Tamoxifen metabolism
WP691
38
2
0.12
16.94
0.0063
0.016
CYP1A1, CYP1A2
NOD pathway
WP1433
39
2
0.12
16.50
0.0066
0.016
PYCARD, ACAP1
Estrogen metabolism
WP697
44
2
0.14
14.63
0.0083
0.0176
CYP1A1, CYP1A2
Selenium Metabolism and
Selenoproteins
WP28
49
2
0.15
13.14
0.0102
0.0193
SELENBP1, EEFSEC
cytochrome P450
WP43
65
2
0.20
9.90
0.0175
0.027
CYP1A1, CYP1A2
Proteasome Degradation
WP183
65
2
0.20
9.90
0.0175
0.027
PSMB4, UBA7
Integrated Pancreatic Cancer
Pathway
WP2256
181
3
0.56
5.33
0.0191
0.0271
BRCA2, DCC, MST1
USER DATA & PARAMETERS - N= 137 genes submitted, Genes mapped to unique Entrez Gene IDs: 134, Organism: hsapiens, Id Type: gene_symbol, Ref
Set: entrezgene, Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH, Minimum: 2, Enrichment Analyses: KEGG and Wikipathways
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category (O), expected number in the
category (E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted by the multiple test adjustment (adjP).
Dataset S2.5. Pathway enrichment results using all genes underlying regions of
elevated FST in the pooled domestic cats relative to the pooled wildcats

Dataset S2.6. Variant calls per individual breed pools

Dataset S2.7. SNPs analyses of KIT in the domestic cat
ID
Breed1
Type2
Exon(E) or intron(I) nucleotide site
10
281
396
522
531
-67
1035
1036
-5
1473
1479
-18
1617
+34
2054
2325
-30
-3
+37
2805
2856
2862
E1
E2
E3
E3
E3
I3
E6
E6
I8
E9
E9
I9
E10
I10
E14
E16
I17
I17
I18
E20
E21
E21
Wild-type sequence
G
A
G
T
C
A
G
C
T
G
G
G
T
G
G
C
T
C
T
T
A
C
4910
PE
Black
G
M
G
Y
C
A
G
C
T
G
G
R
C
G
G
Y
T
C
W
T
R
C
4406
RB
Orange
G
M
R
C
Y
M
G
C
Y
G
G
G
W
R
G
Y
Y
Y
A
Y
G
C
9299
RG
Seal pt
G
A
G
K
C
M
S
M
T
G
G
G
C
R
G
C
Y
Y
A
T
R
Y
5337
PE
White
R
A
R
Y
Y
M
G
C
Y
G
G
G
Y
R
G
C
Y
Y
W
T
A
C
10630
AC
Bicolor
G
M
G
Y
C
A
G
C
T
G
G
R
C
G
G
Y
T
C
W
T
R
C
H10013
RB
Bicolor
G
A
R
Y
Y
A
G
C
T
G
G
G
Y
G
G
C
T
C
T
T
R
Y
5779
RG
Bicolor
G
A
G
T
C
A
G
C
T
G
G
G
C
G
G
C
T
C
W
T
A
C
11555
RG
Bicolor
G
A
G
T
C
A
G
C
T
G
G
R
C
G
R
C
T
C
W
T
A
C
11556
RG
Bicolor
G
A
G
T
C
A
G
C
T
G
G
R
C
G
G
C
T
C
W
T
A
C
10660
BI
Gloves
G
C
G
C
C
A
C
A
T
G
G
A
T
G
G
C
T
C
A
T
R
T
11558
RG
Mitted
G
A
R
K
Y
A
G
C
Y
G
G
G
Y
G
R
C
T
C
T
T
R
C
H11743
RB
Van
G
A
G
T
C
A
G
C
T
G
G
G
C
G
G
C
T
C
T
T
A
C
8592
RB
Van
G
M
G
Y
C
M
S
M
Y
G
G
G
Y
G
G
C
Y
Y
W
T
R
Y
11608
TV
Van
G
A
G
T
C
A
G
C
T
G
G
G
C
G
G
C
T
C
T
T
A
C
11618
TV
Van
G
A
R
Y
C
M
G
C
T
R
R
G
W
G
G
C
Y
Y
W
T
R
C
NM_001009
837.3
/
/
G
A
A
C
T
/
G
C
/
G
G
/
T
/
G
C
/
/
/
T
G
C
ENSFCAT0
0000003113
AB
Cinnamon
/
A
G
T
C
A
G
C
T
G
G
G
T
G
G
C
T
C
T
T
A
C
Amino Acid change
A4T
N94T
E345D
H346N
A491T
R685K
1Breed designations: RB = random bred, PE = Persian, RG = Ragdoll, AC = American Curl, BI = Birman, TV = Turkish Van, AB =
Abyssinian. 2Type indicates coloration of the cat, including the white spotting patterns. Some colors have epistasis, for example,
dominant white. A cat may be a seal point (pt) or a bicolor, but dominant white will override these colors as melanocytes are
absent, preventing the expression of the melanin. Alleles for bicolor and van may be different between breeds and may be
additive. Birmans all have “gloves’ and are pointed according to breed standards. Mitted Ragdolls may or may not be pointed.
3Cats from the WALTHAM pedigree used for the linkage analysis of the Spotting locus.

G (gloves) implies the c.1035_1036delinsCA haplotype, the gloves haplotype. N implies
the wildtype allele. 1. Gloves/mitted are cats with white feet. 2. Solid implies a cat with no
white spotting pattern. 3. Ambiguous implies a cat with a white spotting pattern that is
epistatic and may mask the glove pattern, such as bicolor or dominant white. 4. Cats with
no phenotypic description available are listed as unknown. 5.Two random bred cats were
included from the WALTHAM pedigree.
Dataset S2.8. Frequency of the glove haplotype in cat breed
!
Observed Genotypes/Phenotypes
Breed
No.
Gloves/mitted
Solid
Ambiguous
Unknown
!
Frequency
c.
1035_1036d
elinsCA
haplotype
GG
GN
NN
GG
GN
NN
GG
GN
NN
GG
GN
NN
Birman
182
177
3
2
0
0
0
0
0
0
0
0
0
0.98
Birman
outcrosses
5
0
0
0
0
5
0
0
0
0
0
0
0
0.50
Ragdoll
171
1
7
19
0
11
30
0
7
55
0
15
26
0.12
Random
Bred
315
0
0
3
2
15
48
2
10
56
4
22
153
0.10
American
Shorthair
11
0
0
0
0
0
5
0
0
1
0
0
5
0.00
American
Wirehair
3
0
0
0
0
0
0
0
0
1
0
0
2
0.00
Egyptian
Mau
6
0
0
0
0
1
5
0
0
0
0
0
0
0.08
Exotic
10
0
0
0
0
0
0
0
0
0
0
1
9
0.05
Japanese
Bobtail
12
0
0
0
0
0
4
0
0
7
0
0
1
0.00
Korat
11
0
0
0
0
0
11
0
0
0
0
0
0
0.00
Maine Coon
10
0
0
0
0
2
1
0
0
1
0
0
6
0.10
Manx
13
0
0
0
0
1
1
0
4
7
0
0
0
0.19
Norwegian
Forest Cat
11
0
0
0
0
0
3
0
0
3
0
0
5
0.00
Persian
8
0
0
0
0
0
5
0
0
1
0
0
2
0.00
Russian
Blue
11
0
0
0
0
0
11
0
0
0
0
0
0
0.00
Seychellois
2
0
2
0
0
0
0
0
0
0
0
0
0
0.50
Siamese
52
0
0
0
0
3
49
0
0
0
0
0
0
0.03
Siberian
20
0
0
0
1
3
2
1
0
12
0
0
1
0.17
Singapura
8
0
0
0
0
0
8
0
0
0
0
0
0
0.00
Snowshoe
2
0
0
2
0
0
0
0
0
0
0
0
0
0.00
Sphynx
14
0
0
0
0
0
0
1
0
2
3
6
2
0.50
Turkish
Angora
14
0
0
0
0
0
0
0
0
12
0
0
2
0.00
Turkish Van
20
0
0
0
0
0
1
0
1
17
0
0
1
0.02
TOTAL
911
178
12
26
3
41
183
4
22
176
7
44
215
/

Genomic Primers
Exon
Exon
Size
(bp)
Product
Size
(bp)
Forward Primer 5’-3’
Reverse Primer 5’-3’
Tm/[Mg2+]
µM
1
154
173
TCTGGGGGCTCGGCTTTGC
GTCCGCGGCGCTCTCCCAC
60/1.75
2
270
366
ATGCTTTATTTCGCCAAGGA
TCCAAAGCATAGCATGAAAGAA
58/2.25
3
282
395
GCAAAGAGAAACGTCGGAGT
CCCAGAAGAACGCGAGAA
58/1.75
4
140
237
AGGCCACCGAATAAGTTGTG
CGGGCTGTTTTCCTTGATCCA
58/2.25
5
169
361
GACAGACTTGTCATGATGCTTTATT
CATTTATAGAGATACGCTTG
58/2.25
6
190
248
TTCATTAACATCTTCCCTATGATGAA
AGGCCCTGGTAAGCCAAG
60/2.00
7
116
245
CAGGCCCTTCACAAGTGATT
CCAACACGAGCCACAACTTA
58/2.25
8
115
212
GGTGAGGTTTTCCAGCAGTC
GTCCTTCCCTTACGCATGTC
58/2.25
9
194
295
CTTTCTGGAGTAAATCGGGTTG
TGACTGATATGGCAGGCAGA
60/1.75
10-11
107-127
394
CTGCCAATAGATTGTGATTCC
AAAGCCCCGGCTTCATAC
58/2.25
12-13
105-111
380
ACACCACCACGTGCTCTCT
TTTGAAAGATAATAAAAGGTAATTTGG
58/2.25
14
151
496
TTGCCAGCAGTGTCAATAGG
TTCTGATTTTGTGCCTCGAA
58/1.75
15
92
259
CTCCCCTTTTTCCCATTTTG
GCACTGTTATTGGGGGCTAC
58/2.25
16
128
245
CCTTGCTTTGAGGTTTAATTGCT
CTCCAAAGTGGGGCTTGG
58/1.75
17
123
263
CGAAACACACATCATTCAGAG
GGGTACTTACGTTTCCTTTG
60/1.75
18-19
112-100
456
CCTCAGCAGGAGCAATGTCT
AGGGGAAGCACTATCTGAAGG
58/1.75
20
106
288
GCCCTGGAATTTGAGATTGT
AAAGGTCTTCACCCCCAGAG
60/2.00
21
132
159
GGTGTAGGGACTGGCATGTAA
GAACCAAAAGAAGAGGGATCG
60/1.75
5’UTR
/
185
GeneRacer 5’ Primer (Invitrogen)
GAGCAGGAGGAGCAGGACG
62/1.50
Primer name
Allele Specific PCR primers
KITgloA-VIC
168
GGCATATCCCAAGCCTGACA
AGGCCCTGGTAAGCCAAG
60/1.50
KITgloB-FAM
168
GGCATATCCCAAGCCTGAGC
AGGCCCTGGTAAGCCAAG
60/1.50
Primer name
Microsatellites primers
UCDC259b
117
AGACCTTCAGAGTTGCCAGTG
TGTCCTCATTACCGTCCTACC
58/2.00
UCDC489
212
GCTCTGCTCCAACATTGC
GGACCATGCTAATCTAATCGAC
58/2.00
UCDC487
158
CCTCCTCCTCAACAACCTG
CTTGAAGCATTGTAGCTGGAAC
58/2.00
UCDC443
148
GCAACTAGCCAGCTCCAG
ACTCCACTTGTTGACGATCC
58/2.00
!
Dataset S2.9. Primer sequences and PCR condition for the analysis of feline KIT

Dataset S2.10. Pathway enrichment results using all genes underlying regions
of low Hp in the pooled domestic cats
KEGG Pathway
Pathway ID
C
O
E
R
rawP
adjP
Genes
Purine metabolism
230
162
6
0.73
8.23
9.80E-05
0.0023
PDE5A, ENTPD1, POLR2G, PDE1B,
POLD4, PNPT1
Metabolic pathways
1100
1130
16
5.08
3.15
5.84E-05
0.0023
ACADS, GCLM, ATP6V1D, CYP1A1,
POLR2G, GLS2, CYP1A2, GALNT8,
B3GAT3, CS, PI4KA, PIGU, GALNT10,
POLD4, GANAB, EXTL2
Ubiquitin mediated
proteolysis
4120
135
5
0.61
8.23
0.0004
0.0061
TRIM37, UBE2K, ITCH, UBE2L3, PPIL2
Pyrimidine metabolism
240
99
4
0.45
8.98
0.0011
0.0126
ENTPD1, POLR2G, POLD4, PNPT1
Axon guidance
4360
129
4
0.58
6.89
0.0028
0.0222
SEMA7A, MAPK1, DCC, RHOD
Regulation of actin
cytoskeleton
4810
213
5
0.96
5.22
0.0029
0.0222
SSH3, MAPK1, NCKAP1L, CHRM1,
FGF12
RNA degradation
3018
71
3
0.32
9.39
0.0041
0.0236
PNPT1, PAN2, EDC3
Long-term potentiation
4720
70
3
0.31
9.53
0.0039
0.0236
GRIA1, MAPK1, PPP1R1A
Homologous recombination
3440
28
2
0.13
15.88
0.0070
0.0268
TOP3B, POLD4
Jak-STAT signaling pathway
4630
155
4
0.70
5.74
0.0054
0.0268
IL23A, IL6ST, IL12B, STAT2
Protein processing in
endoplasmic reticulum
4141
165
4
0.74
5.39
0.0067
0.0268
EIF2S1, UFD1L, DERL3, GANAB
Glycosaminoglycan
biosynthesis - heparan sulfate
534
26
2
0.12
17.10
0.0061
0.0268
EXTL2, B3GAT3
Mucin type O-Glycan
biosynthesis
512
30
2
0.13
14.82
0.0081
0.0287
GALNT10, GALNT8
African trypanosomiasis
5143
35
2
0.16
12.70
0.0109
0.0358
VCAM1, IL12B
Endocytosis
4144
201
4
0.90
4.42
0.0132
0.0405
PARD6A, ADRBK1, CLTCL1, ITCH
Tryptophan metabolism
380
42
2
0.19
10.59
0.0154
0.0443
CYP1A1, CYP1A2
Wikipathway
Adipogenesis
WP236
130
7
0.58
11.97
2.21E-06
7.29E-05
EBF1, MIF, ASIP, BSCL2, AHR, IL6ST,
STAT2
AhR pathway
WP2100
39
3
0.18
17.10
0.0007
0.0115
CYP1A1, CYP1A2, AHR
Fatty Acid Omega Oxidation
WP206
15
2
0.07
29.64
0.002
0.022
CYP1A1, CYP1A2
Integrated Breast Cancer
Pathway
WP1984
68
3
0.31
9.81
0.0036
0.0297
MAPK1, AHR, SMEK2
Regulation of Actin
Cytoskeleton
WP51
157
4
0.71
5.66
0.0057
0.0336
SSH3, MAPK1, FGF12, CHRM1
Physiological and
Pathological Hypertrophy of
the Heart
WP1528
26
2
0.12
17.10
0.0061
0.0336
MAPK1, IL6ST
USER DATA & PARAMETERS - N= 208 genes submitted, Genes mapped to unique Entrez Gene IDs: 194, Organism: hsapiens, Id Type: gene_symbol, Ref
Set: entrezgene, Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH, Minimum: 2, Enrichment Analyses: KEGG and Wikipathways
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category (O), expected number in the
category (E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted by the multiple test adjustment (adjP).

Dataset S2.11. Pathway enrichment results using genes underlying regions of
elevated FST in the pooled domestic cats relative to the pooled wildcats and
genes underlying regions of low Hp in the pooled domestic cats
KEGG Pathway
Pathway ID
C
O
E
R
rawP
adjP
Genes
Metabolic pathways
1100
1130
24
8.33
2.88
4.40E-06
0.0003
ACADS, ARG2, GCLM, POLR2G,
B3GAT3, PIGH, PI4KA, PIGU, HSD3B7,
RDH11, ATP6V1D, CYP1A1, NDUFA2,
CYP1A2, GLS2, GALNT8, CS, GMPPB,
RDH12, GALNT10, ACADVL, POLD4,
GANAB, EXTL2
Homologous recombination
3440
28
4
0.21
19.37
5.16E-05
0.0015
TOP3B, BRCA2, POLD4, RAD51B
Ubiquitin mediated
proteolysis
4120
135
7
1
7.03
6.86E-05
0.0015
UBE3A, TRIM37, UBE2K, UBA7, ITCH,
UBE2L3, PPIL2
Axon guidance
4360
129
6
0.95
6.31
0.0004
0.0066
SEMA7A, SEMA3G, MAPK1, DCC,
RHOD, PLXNB2
Systemic lupus erythematosus
5322
136
6
1
5.98
0.0005
0.0066
HIST2H3D, HIST2H2BE, HIST3H2BB,
HIST2H2AC, HIST2H2AB, HIST3H2A
NOD-like receptor signaling
pathway
4621
58
4
0.43
9.35
0.0009
0.0099
MAPK1, NLRP3, PYCARD, PSTPIP1
Purine metabolism
230
162
6
1.19
5.02
0.0013
0.0107
PDE5A, ENTPD1, POLR2G, PDE1B,
POLD4, PNPT1
Retinol metabolism
830
64
4
0.47
8.48
0.0013
0.0107
RDH12, CYP1A1, CYP1A2, RDH11
SNARE interactions in
vesicular transport
4130
36
3
0.27
11.30
0.0024
0.0176
STX4, STX1B, STX5
Regulation of actin
cytoskeleton
4810
213
6
1.57
3.82
0.0052
0.0343
SSH3, CD14, MAPK1, NCKAP1L,
CHRM1, FGF12
Pyrimidine metabolism
240
99
4
0.73
5.48
0.0063
0.0378
ENTPD1, POLR2G, POLD4, PNPT1
Wikipathway
Adipogenesis
WP236
130
8
0.96
8.35
5.96E-06
0.0003
EBF1, MIF, BSCL2, SLC2A4, IL6ST,
ASIP, AHR, STAT2
AhR pathway
WP2100
39
4
0.29
13.91
0.0002
0.0051
CYP1A1, FLG, CYP1A2, AHR
Integrated Breast Cancer
Pathway
WP1984
68
4
0.50
7.98
0.0016
0.0255
BRCA2, MAPK1, AHR, SMEK2
Hypothetical Network for
Drug Addiction
WP666
35
3
0.26
11.62
0.0022
0.0255
GRIA1, MAPK1, NISCH
mRNA processing
WP411
132
5
0.97
5.14
0.003
0.0255
NXF1, FUS, SF3B4, PTBP2, CLK3
NOD pathway
WP1433
39
3
0.29
10.43
0.003
0.0255
NLRP3, PYCARD, ACAP1
Regulation of Actin
Cytoskeleton
WP51
157
5
1.16
4.32
0.0063
0.0357
SSH3, CD14, MAPK1, CHRM1, FGF12
Fatty Acid Omega Oxidation
WP206
15
2
0.11
18.08
0.0053
0.0357
CYP1A1, CYP1A2
Mitochondrial LC-Fatty Acid
Beta-Oxidation
WP368
16
2
0.12
16.95
0.0061
0.0357
ACADS, ACADVL
USER DATA & PARAMETERS - N= 345 genes submitted, Genes mapped to unique Entrez Gene IDs: 378, Organism: hsapiens, Id Type: gene_symbol, Ref
Set: entrezgene, Significance Level: .05, Statistics Test: Hypergeometric, MTC: BH, Minimum: 2, Enrichment Analyses: KEGG and Wikipathways
COLUMN HEADINGS - number of reference genes in the category (C), number of genes in the gene set and also in the category (O), expected number in the
category (E), Ratio of enrichment (R), p value from hypergeometric test (rawP), and p value adjusted by the multiple test adjustment (adjP).

Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated Gene
Name
Description
Overlap With Low
Domestic Hp
X
41887246
41908184
ENSFCAG00000002568
HDAC6
histone deacetylase 6
X
41911909
41912610
ENSFCAG00000011221
ERAS
ES cell expressed Ras
X
41913754
41919251
ENSFCAG00000011223
PCSK1N
proprotein convertase subtilisin/kexin type 1 inhibitor
X
41934479
41938238
ENSFCAG00000002569
TIMM17B
translocase of inner mitochondrial membrane 17 homolog B (yeast)
X
41938194
41942483
ENSFCAG00000002570
PQBP1
polyglutamine binding protein 1
X
41942562
41951493
ENSFCAG00000002571
SLC35A2
solute carrier family 35 (UDP-galactose transporter), member A2
X
41952709
41957926
ENSFCAG00000022467
PIM2
pim-2 oncogene
X
41961788
41988147
ENSFCAG00000002572
OTUD5
OTU domain containing 5
X
41991981
41998591
ENSFCAG00000002579
KCND1
potassium voltage-gated channel, Shal-related subfamily, member 1
X
42002178
42025194
ENSFCAG00000002573
GRIPAP1
GRIP1 associated protein 1
X
42059037
42068974
ENSFCAG00000002574
TFE3
transcription factor binding to IGHM enhancer 3
X
42086076
42092788
ENSFCAG00000028936
CCDC120
coiled-coil domain containing 120
X
42093264
42096118
ENSFCAG00000002576
PRAF2
PRA1 domain family, member 2
X
42096851
42101817
ENSFCAG00000002577
X
42129150
42136833
ENSFCAG00000003818
GPKOW
G patch domain and KOW motifs
X
42149508
42149825
ENSFCAG00000028597
X
42872212
42934297
ENSFCAG00000015279
CCNB3
cyclin B3
X
X
42969241
43078360
ENSFCAG00000015283
X
X
46413121
46442443
ENSFCAG00000008699
GNL3L
guanine nucleotide binding protein-like 3 (nucleolar)-like
X
46490447
46490559
ENSFCAG00000022607
5S_rRNA
5S ribosomal RNA
X
49084155
49256064
ENSFCAG00000008079
ARHGEF9
Cdc42 guanine nucleotide exchange factor (GEF) 9
X
X
49256901
49256994
ENSFCAG00000020519
X
49353869
49353981
ENSFCAG00000030238
5S_rRNA
5S ribosomal RNA
X
53226451
53260915
ENSFCAG00000030156
ZC4H2
zinc finger, C4H2 domain containing
X
X
53707791
53708303
ENSFCAG00000022560
X
X
53752218
53752715
ENSFCAG00000026187
X
X
53897284
53962444
ENSFCAG00000013821
MSN
moesin
X
53999183
53999682
ENSFCAG00000031039
X
54021127
54021234
ENSFCAG00000030106
5S_rRNA
5S ribosomal RNA
X
57120311
57122215
ENSFCAG00000013727
PJA1
praja ring finger 1, E3 ubiquitin protein ligase
X
57461705
57487956
ENSFCAG00000000752
FAM155B
family with sequence similarity 155, member B
X
X
62121214
62344089
ENSFCAG00000014128
ZDHHC15
zinc finger, DHHC-type containing 15
X
62258432
62259126
ENSFCAG00000030281
X
62407545
62409116
ENSFCAG00000027322
MAGEE2
melanoma antigen family E, 2
X
62859874
62859986
ENSFCAG00000027539
5S_rRNA
5S ribosomal RNA
X
62950563
62950675
ENSFCAG00000027233
5S_rRNA
5S ribosomal RNA
X
62990509
62991208
ENSFCAG00000025177
X
64307801
64308823
ENSFCAG00000024786
CYSLTR1
cysteinyl leukotriene receptor 1
X
64322586
64322696
ENSFCAG00000024593
5S_rRNA
5S ribosomal RNA
X
64453218
64453330
ENSFCAG00000022019
5S_rRNA
5S ribosomal RNA
X
64983078
64984100
ENSFCAG00000012066
P2RY10
purinergic receptor P2Y, G-protein coupled, 10
X
64997854
64997966
ENSFCAG00000027429
5S_rRNA
5S ribosomal RNA
X
65054928
65056011
ENSFCAG00000022899
X
65077240
65077352
ENSFCAG00000023385
5S_rRNA
5S ribosomal RNA
X
65091920
65092786
ENSFCAG00000023690
X
65852774
65860885
ENSFCAG00000002301
TBX22
T-box 22
X
69515199
69515308
ENSFCAG00000023760
5S_rRNA
5S ribosomal RNA
X
69533113
69538158
ENSFCAG00000012662
CYLC1
cylicin, basic protein of sperm head cytoskeleton 1
X
69578192
69578304
ENSFCAG00000022168
5S_rRNA
5S ribosomal RNA
X
69687439
69829396
ENSFCAG00000009130
RPS6KA6
ribosomal protein S6 kinase, 90kDa, polypeptide 6
X
70028313
70186830
ENSFCAG00000005781
HDX
highly divergent homeobox
X
70466196
70466308
ENSFCAG00000028603
5S_rRNA
5S ribosomal RNA
X
72446722
72446834
ENSFCAG00000024434
5S_rRNA
5S ribosomal RNA
X
74987292
74987597
ENSFCAG00000024785
X
76506764
76565232
ENSFCAG00000025687
X
76745486
76757291
ENSFCAG00000031194
X
76768969
76774841
ENSFCAG00000027080
X
76776829
76779222
ENSFCAG00000029591
X
76853016
76853919
ENSFCAG00000028074
X
77857129
77857212
ENSFCAG00000028826
X
77885307
77888089
ENSFCAG00000031149
X
78058091
78058203
ENSFCAG00000024847
5S_rRNA
5S ribosomal RNA
X
80450058
80592747
ENSFCAG00000013438
PCDH19
protocadherin 19
X
X
80616295
80616399
ENSFCAG00000023489
5S_rRNA
5S ribosomal RNA
X
X
80649550
80650477
ENSFCAG00000026700
ANXA2
annexin A2
X
X
80741994
80757092
ENSFCAG00000024939
TNMD
tenomodulin
Dataset S2.12(a). Genes underlying regions of high FST in the pooled domestic
cat X-chromosome variant dataset relative to the pooled wildcat variant dataset

X
82163945
82164473
ENSFCAG00000023241
X
X
82185302
82186069
ENSFCAG00000022838
X
X
82201194
82201535
ENSFCAG00000013057
BEX5
brain expressed, X-linked 5
X
X
82233303
82256641
ENSFCAG00000013704
X
X
83182109
83182975
ENSFCAG00000013517
MORF4L2
mortality factor 4 like 2
X
83212584
83234142
ENSFCAG00000013518
GLRA4
glycine receptor, alpha 4
X
83215743
83219091
ENSFCAG00000028808
TMEM31
transmembrane protein 31
X
83280484
83296694
ENSFCAG00000029818
PLP1
proteolipid protein 1
X
83331532
83332137
ENSFCAG00000000424
RAB9B
RAB9B, member RAS oncogene family
X
83491286
83491820
ENSFCAG00000026463
X
83499961
83528634
ENSFCAG00000006496
FAM199X
family with sequence similarity 199, X-linked
X
83591368
83596306
ENSFCAG00000007095
ESX1
ESX homeobox 1
X
83679272
83679384
ENSFCAG00000025445
5S_rRNA
5S ribosomal RNA
X
84656031
84656372
ENSFCAG00000024474
X
85860177
85861301
ENSFCAG00000026273
X
85885076
85885160
ENSFCAG00000024140
5S_rRNA
5S ribosomal RNA
X
103563484
103563596
ENSFCAG00000029982
5S_rRNA
5S ribosomal RNA
X
103728395
103728504
ENSFCAG00000031724
5S_rRNA
5S ribosomal RNA
X
105790212
105795802
ENSFCAG00000022024
APLN
apelin
X
105873179
105898315
ENSFCAG00000008070
XPNPEP2
X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound
X
105876930
105877062
ENSFCAG00000020596
X
105908858
105920969
ENSFCAG00000005733
SASH3
SAM and SH3 domain containing 3
X
105928883
105963235
ENSFCAG00000025956
ZDHHC9
zinc finger, DHHC-type containing 9
X
121763118
121818915
ENSFCAG00000004331
MAMLD1
mastermind-like domain containing 1
X
121893254
121967078
ENSFCAG00000004332
MTM1
myotubularin 1
X
125095537
125102445
ENSFCAG00000011399
FAM50A
family with sequence similarity 50, member A
X
125116074
125128684
ENSFCAG00000011400
PLXNA3
plexin A3
X
125134531
125136460
ENSFCAG00000029129
LAGE3
L antigen family, member 3
X
125140852
125143560
ENSFCAG00000025607
UBL4A
ubiquitin-like 4A
X
125144336
125145769
ENSFCAG00000022989
SLC10A3
solute carrier family 10 (sodium/bile acid cotransporter family), member 3
X
125152456
125159000
ENSFCAG00000011403
FAM3A
family with sequence similarity 3, member A
X
125167043
125177827
ENSFCAG00000011404
G6PD
glucose-6-phosphate dehydrogenase
X
125182326
125199683
ENSFCAG00000029840
IKBKG
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
X
125244852
125245838
ENSFCAG00000028188
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated Gene
Name
Description
Overlap With Low
Domestic Hp
Dataset S2.12(b). Genes underlying regions of high FST in the pooled domestic
cat X-chromosome variant dataset relative to the pooled wildcat variant dataset

Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap With
High FST (>1.5)
X
21630
63492
ENSFCAG00000025306
X
69519
101606
ENSFCAG00000015077
PPP2R3B
protein phosphatase 2, regulatory subunit B'', beta
X
193651
210731
ENSFCAG00000010308
X
216285
223908
ENSFCAG00000013263
X
258750
260256
ENSFCAG00000022728
X
297649
299085
ENSFCAG00000029324
X
788985
801017
ENSFCAG00000030897
IL3RA
interleukin 3 receptor, alpha (low affinity)
X
802775
805108
ENSFCAG00000001211
SLC25A6
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 6
X
810005
827797
ENSFCAG00000014304
ASMTL
acetylserotonin O-methyltransferase-like
X
832290
833503
ENSFCAG00000029147
X
832943
833542
ENSFCAG00000025999
X
836793
839803
ENSFCAG00000031505
ASMT
acetylserotonin O-methyltransferase
X
982130
1057940
ENSFCAG00000025503
X
1076513
1078597
ENSFCAG00000012522
ZBED1
zinc finger, BED-type containing 1
X
2583245
2591210
ENSFCAG00000022434
X
3110376
3385224
ENSFCAG00000000375
X
4013126
4013238
ENSFCAG00000024922
5S_rRNA
5S ribosomal RNA
X
4042639
4093472
ENSFCAG00000023323
HDHD1
haloacid dehalogenase-like hydrolase domain containing 1
X
4206218
4291197
ENSFCAG00000024019
STS
steroid sulfatase (microsomal), isozyme S
X
4770564
4800388
ENSFCAG00000004082
PNPLA4
patatin-like phospholipase domain containing 4
X
5336558
5408176
ENSFCAG00000004854
KAL1
Kallmann syndrome 1 sequence
X
6295756
6440915
ENSFCAG00000011563
TBL1Y
transducin (beta)-like 1, Y-linked
X
6470618
6495329
ENSFCAG00000021932
GPR143
G protein-coupled receptor 143
X
6513656
6514431
ENSFCAG00000025783
X
6596578
6677533
ENSFCAG00000011183
SHROOM2
shroom family member 2
X
6690557
6691192
ENSFCAG00000028772
X
6710553
6711562
ENSFCAG00000022520
X
6789548
6865297
ENSFCAG00000011192
WWC3
WWC family member 3
X
6780137
6953135
ENSFCAG00000007631
CLCN4
chloride channel, voltage-sensitive 4
X
7112953
7216047
ENSFCAG00000002582
MID1
midline 1 (Opitz/BBB syndrome)
X
7699738
7710351
ENSFCAG00000022393
HCCS
holocytochrome c synthase
X
7720243
7791414
ENSFCAG00000002122
ARHGAP6
Rho GTPase activating protein 6
X
7830735
7835138
ENSFCAG00000023640
AMELX
Amelogenin
X
8074048
8074539
ENSFCAG00000030523
X
8099270
8099635
ENSFCAG00000024727
X
8259014
8271418
ENSFCAG00000002794
MSL3
male-specific lethal 3 homolog (Drosophila)
X
8513291
8513384
ENSFCAG00000017961
X
9076358
9162154
ENSFCAG00000006682
FRMPD4
FERM and PDZ domain containing 4
X
9305798
9308923
ENSFCAG00000027513
TLR8
Toll-like receptor 8
X
9354701
9356802
ENSFCAG00000022748
X
9885613
9886440
ENSFCAG00000027185
X
9931463
9964979
ENSFCAG00000012437
EGFL6
EGF-like-domain, multiple 6
X
9981863
9982885
ENSFCAG00000024286
X
10023119
10023736
ENSFCAG00000023992
RAB9A
RAB9A, member RAS oncogene family
X
10027827
10039663
ENSFCAG00000023912
X
10039520
10081402
ENSFCAG00000014870
OFD1
oral-facial-digital syndrome 1
X
10103285
10143181
ENSFCAG00000014877
GPM6B
glycoprotein M6B
X
10305715
10316101
ENSFCAG00000014428
GEMIN8
gem (nuclear organelle) associated protein 8
X
10529330
10529398
ENSFCAG00000025105
X
10538216
10538293
ENSFCAG00000027438
X
10784014
10784129
ENSFCAG00000022459
5S_rRNA
5S ribosomal RNA
X
10741200
10911440
ENSFCAG00000011448
GLRA2
glycine receptor, alpha 2
X
11018197
11033965
ENSFCAG00000029176
FANCB
Fanconi anemia, complementation group B
X
11041578
11095832
ENSFCAG00000022388
MOSPD2
motile sperm domain containing 2
X
11187292
11187374
ENSFCAG00000029611
X
11286501
11288251
ENSFCAG00000031484
CBX4
chromobox homolog 4
X
11413677
11441669
ENSFCAG00000010484
ASB9
ankyrin repeat and SOCS box containing 9
Dataset S2.13(a). Genes underlying regions of low Hp in the pooled domestic cat
X-chromosome variant dataset following annotation of 100kb windows that fell
below 1.5 standard deviations from the mean Hp

X
11450862
11475292
ENSFCAG00000022236
ASB11
ankyrin repeat and SOCS box containing 11
X
11478140
11488483
ENSFCAG00000010727
PIGA
phosphatidylinositol glycan anchor biosynthesis, class A
X
11497779
11531651
ENSFCAG00000010485
FIGF
c-fos induced growth factor (vascular endothelial growth factor D)
X
11532692
11621888
ENSFCAG00000010486
PIR
pirin (iron-binding nuclear protein)
X
11631474
11678324
ENSFCAG00000010487
BMX
BMX non-receptor tyrosine kinase
X
11681716
11720452
ENSFCAG00000009320
ACE2
Angiotensin-converting enzyme 2 Processed angiotensin-converting enzyme 2
X
11746176
11777544
ENSFCAG00000009328
TMEM27
transmembrane protein 27
X
11828552
11828664
ENSFCAG00000029736
5S_rRNA
5S ribosomal RNA
X
11788172
11901542
ENSFCAG00000031216
CA5B
carbonic anhydrase VB, mitochondrial
X
11906051
11933524
ENSFCAG00000009333
X
11936136
11962265
ENSFCAG00000024224
AP1S2
adaptor-related protein complex 1, sigma 2 subunit
X
12787190
12837643
ENSFCAG00000006523
TXLNG
taxilin gamma
X
12837168
12864998
ENSFCAG00000028919
RBBP7
retinoblastoma binding protein 7
X
12996604
13134277
ENSFCAG00000006527
REPS2
RALBP1 associated Eps domain containing 2
X
13935586
13935741
ENSFCAG00000018915
X
14086539
14119271
ENSFCAG00000006437
BEND2
BEN domain containing 2
X
14172289
14250913
ENSFCAG00000006438
SCML2
sex comb on midleg-like 2 (Drosophila)
X
17399416
17399526
ENSFCAG00000017180
5S_rRNA
5S ribosomal RNA
X
17175933
17401205
ENSFCAG00000026807
CNKSR2
connector enhancer of kinase suppressor of Ras 2
X
17833482
17848892
ENSFCAG00000023168
X
17988539
18006475
ENSFCAG00000023221
X
18029515
18031154
ENSFCAG00000010060
ZNF645
zinc finger protein 645
X
18790237
18791979
ENSFCAG00000013616
DDX53
DEAD (Asp-Glu-Ala-Asp) box polypeptide 53
X
19109565
19159869
ENSFCAG00000031503
PTCHD1
patched domain containing 1
X
19250902
19251014
ENSFCAG00000027204
5S_rRNA
5S ribosomal RNA
X
19308144
19308597
ENSFCAG00000031952
X
19393444
19413380
ENSFCAG00000004028
PRDX4
peroxiredoxin 4
X
19420080
19443002
ENSFCAG00000004030
ACOT9
acyl-CoA thioesterase 9
X
19476530
19479076
ENSFCAG00000004032
SAT1
spermidine/spermine N1-acetyltransferase 1
X
19912217
19915290
ENSFCAG00000022717
X
19931048
19934125
ENSFCAG00000026176
X
20018240
20085226
ENSFCAG00000002134
PDK3
pyruvate dehydrogenase kinase, isozyme 3
X
20104464
20200081
ENSFCAG00000002136
PCYT1B
phosphate cytidylyltransferase 1, choline, beta
X
20249684
20553632
ENSFCAG00000002138
POLA1
polymerase (DNA directed), alpha 1, catalytic subunit
X
20868777
20869679
ENSFCAG00000031841
FELCATV1R3
vomeronasal 1 receptor felCatV1R3
X
26713585
26713773
ENSFCAG00000028835
X
26746658
26767210
ENSFCAG00000022029
X
26860944
26917110
ENSFCAG00000028265
X
26971105
26971226
ENSFCAG00000029796
X
30543947
30544592
ENSFCAG00000030015
X
30661122
30662084
ENSFCAG00000030986
MAGEB16
melanoma antigen family B, 16
X
30790586
30849071
ENSFCAG00000018231
CXorf22
chromosome X open reading frame 22
X
38356463
38359279
ENSFCAG00000007766
X
38214551
38413159
ENSFCAG00000007765
EFHC2
EF-hand domain (C-terminal) containing 2
X
38876657
39013854
ENSFCAG00000009445
KDM6A
lysine (K)-specific demethylase 6A
X
39054031
39099121
ENSFCAG00000009449
CXorf36
chromosome X open reading frame 36
X
40057175
40084354
ENSFCAG00000027707
X
40134846
40135831
ENSFCAG00000025461
CHST7
carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 7
X
40163495
40226463
ENSFCAG00000003541
SLC9A7
solute carrier family 9, subfamily A (NHE7, cation proton antiporter 7), member 7
X
41093658
41108251
ENSFCAG00000008192
ELK1
ELK1, member of ETS oncogene family
X
41109294
41118283
ENSFCAG00000028638
UXT
ubiquitously-expressed, prefoldin-like chaperone
X
41127225
41128098
ENSFCAG00000023763
X
41165141
41169982
ENSFCAG00000027976
X
41220128
41306403
ENSFCAG00000022818
ZNF81
zinc finger protein 81
X
41320923
41321464
ENSFCAG00000026947
X
41394530
41395849
ENSFCAG00000030362
X
41428902
41431781
ENSFCAG00000008528
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap With
High FST (>1.5)
Dataset S2.13(b). Genes underlying regions of low Hp in the pooled domestic cat
X-chromosome variant dataset following annotation of 100kb windows that fell
below 1.5 standard deviations from the mean Hp

X
41488558
41490795
ENSFCAG00000027919
X
42702287
42741226
ENSFCAG00000008619
CLCN5
chloride channel, voltage-sensitive 5
X
42750538
42750651
ENSFCAG00000017254
5S_rRNA
5S ribosomal RNA
X
42836383
42851018
ENSFCAG00000031319
AKAP4
A kinase (PRKA) anchor protein 4
X
42872212
42934297
ENSFCAG00000015279
CCNB3
cyclin B3
X
X
42969241
43078360
ENSFCAG00000015283
X
X
43193426
43193530
ENSFCAG00000026630
5S_rRNA
5S ribosomal RNA
X
48251045
48253353
ENSFCAG00000005774
X
48582110
48582823
ENSFCAG00000003939
SPIN4
spindlin family, member 4
X
48716489
48717304
ENSFCAG00000024136
X
48773862
48773974
ENSFCAG00000031522
5S_rRNA
5S ribosomal RNA
X
49049755
49049858
ENSFCAG00000027820
5S_rRNA
5S ribosomal RNA
X
49084155
49256064
ENSFCAG00000008079
ARHGEF9
Cdc42 guanine nucleotide exchange factor (GEF) 9
X
X
53226451
53260915
ENSFCAG00000030156
ZC4H2
zinc finger, C4H2 domain containing
X
X
53639070
53640170
ENSFCAG00000031009
X
53707791
53708303
ENSFCAG00000022560
X
X
53752218
53752715
ENSFCAG00000026187
X
X
57343796
57343908
ENSFCAG00000030304
5S_rRNA
5S ribosomal RNA
X
57461705
57487956
ENSFCAG00000000752
FAM155B
family with sequence similarity 155, member B
X
X
57631690
57632265
ENSFCAG00000028821
X
58391478
58449666
ENSFCAG00000008636
DLG3
discs, large homolog 3 (Drosophila)
X
58465920
58707117
ENSFCAG00000029781
TEX11
testis expressed 11
X
59100432
59101007
ENSFCAG00000021936
X
59107833
59192395
ENSFCAG00000014809
X
59250509
59286633
ENSFCAG00000002182
OGT
O-linked N-acetylglucosamine (GlcNAc) transferase
X
59802421
59806881
ENSFCAG00000023693
CITED1
Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 1
X
59828592
60051076
ENSFCAG00000005065
HDAC8
histone deacetylase 8
X
60058404
60229276
ENSFCAG00000007121
PHKA1
phosphorylase kinase, alpha 1 (muscle)
X
69165483
69166568
ENSFCAG00000011964
POU3F4
POU class 3 homeobox 4
X
73345566
73346382
ENSFCAG00000023461
X
73348095
73348790
ENSFCAG00000030624
X
73490123
73490814
ENSFCAG00000026491
X
75676071
75676176
ENSFCAG00000022654
5S_rRNA
5S ribosomal RNA
X
75747036
75747148
ENSFCAG00000026298
5S_rRNA
5S ribosomal RNA
X
80450058
80592747
ENSFCAG00000013438
PCDH19
protocadherin 19
X
X
80616295
80616399
ENSFCAG00000023489
5S_rRNA
5S ribosomal RNA
X
X
80649550
80650477
ENSFCAG00000026700
ANXA2
annexin A2
X
X
82163945
82164473
ENSFCAG00000023241
X
X
82185302
82186069
ENSFCAG00000022838
X
X
82201194
82201535
ENSFCAG00000013057
BEX5
brain expressed, X-linked 5
X
X
82233303
82256641
ENSFCAG00000013704
X
X
82327996
82335121
ENSFCAG00000010017
Chromosome
Name
Gene Start
(bp)
Gene End
(bp)
Ensembl Gene ID
Associated
Gene Name
Description
Overlap With
High FST (>1.5)
Dataset S2.13(c). Genes underlying regions of low Hp in the pooled domestic cat
X-chromosome variant dataset following annotation of 100kb windows that fell
below 1.5 standard deviations from the mean Hp

1
Genes Underlying Putative Regions of Selection in the Domestic Cat Along the X-Chromosome
Region
Chr:Pos
Gene ID
Gene Name
Description
Domestic
Z(Hp)
Z(FST)
Wildcat
Z(Hp)
1
X:42872212-42934297
ENSFCAG00000015279
CCNB3
cyclin B3
-2.4 to
-1.7
1.6 to!
1.7
-0.8 to!
0.6
X:42969241-43078360
ENSFCAG00000015283
unknown
2
X:49084155-49256064
ENSFCAG00000008079
ARHGEF9
Cdc42 guanine nucleotide exchange factor
(GEF) 9
-2.3
1.5
0.30
3
X:53226451-53260915
ENSFCAG00000030156
ZC4H2
zinc finger, C4H2 domain containing
-2.3 to
-1.6
1.5 to
1.8
0.2 to
0.5
X:53707791-53708303
ENSFCAG00000022560
unknown
X:53752218-53752715
ENSFCAG00000026187
unknown
4
X:57461705-57487956
ENSFCAG00000000752
FAM155B
family with sequence similarity 155,
member B
-3.1 to
-1.5
1.5
-0.8 to
0.5
5
X:80450058-80592747
ENSFCAG00000013438
PCDH19
protocadherin 19
-2.1 to
-1.7
1.60
0.3 to
0.6
X:80616295-80616399
ENSFCAG00000023489
5S_rRNA
5S ribosomal RNA
X:80649550-80650477
ENSFCAG00000026700
ANXA2
annexin A2
6
X:82163945-82164473
ENSFCAG00000023241
unknown
-2.1
1.7
0.6
X:82185302-82186069
ENSFCAG00000022838
unknown
X:82201194-82201535
ENSFCAG00000013057
BEX5
brain expressed, X-linked 5
X:82233303-82256641
ENSFCAG00000013704
unknown
Dataset S2.14. Summary of genes underlying regions of elevated FST and low Hp
along the X-chromosome in domestic cats