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The genomic signature of dog domestication reveals adaptation to a starch-rich diet



The domestication of dogs was an important episode in the development of human civilization. The precise timing and location of this event is debated and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencing of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication. Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.
LETTER doi:10.1038/nature11837
The genomic signature of dog domestication reveals
adaptation to a starch-rich diet
Erik Axelsson
, Abhirami Ratnakumar
, Maja-Louise Arendt
, Khurram Maqbool
, Matthew T. Webster
, Michele Perloski
Olof Liberg
, Jon M. Arnemo
˚ke Hedhammar
& Kerstin Lindblad-Toh
The domestication of dogs was an important episode in the
development of human civilization. The precise timing and loca-
tion of this event is debated
and little is known about the genetic
changes that accompanied the transformation of ancient wolves
into domestic dogs. Here we conduct whole-genome resequencing
of dogs and wolves to identify 3.8 million genetic variants used to
identify 36 genomic regions that probably represent targets for
selection during dog domestication. Nineteen of these regions con-
tain genes important in brain function, eight of which belong to
nervous system development pathways and potentially underlie
behavioural changes central to dog domestication
. Ten genes with
key roles in starch digestion and fat metabolism also show signals
of selection. We identify candidate mutations in key genes and
provide functional support for an increased starch digestion in
dogs relative to wolves. Our results indicate that novel adaptations
allowing the early ancestors of modern dogs to thrive on a diet rich
in starch, relative to the carnivorous diet of wolves, constituted a
crucial step in the early domestication of dogs.
Domestic animals are crucial to modern human society, and it is likely
that the first animal to be domesticated was the dog. Claims of early,
fossilised dog remains include a 33,000-year-old doglike canid from
the Altai Mountains in Siberia
, whereas fossils dating from 12,000–
11,000 years BP found buried together with humans in Israel
could rep-
resent the earliest verified dog remains. Patterns of genomic variation
indicate that dog domestication started at least 10,000 years BP
in south-
ern East Asia
. Dog domestication may however have
been more complex, involving multiple source populations and/or back-
crossing with wolves.
It is unclear why and how dogs were domesticated. Humans may
have captured wolf pups for use in guarding or hunting, resulting in
selection for traits of importance for these new roles. Alternatively, as
humans changed from a nomadic to sedentary lifestyle during the
dawn of the agricultural revolution, wolves may themselves have been
attracted to dumps near early human settlements to scavenge
. Natural
selection for traits allowing for efficient use of this new resource may
have led to the evolution of a variety of scavenger wolves that con-
stituted the ancestors of modern dogs. Regardless of how dog domesti-
cation started, several characteristics separating modern dogs from
wolves, including reduced aggressiveness and altered social cognition
, suggest that behavioural changes were early targets of this
. Dogs also differ morphologically from wolves, showing
reduced skull, teeth and brain sizes
. Artificial selection for tameness
in silver foxes indicates that selection on genetic variation in develop-
mental genes may underlie both behavioural and morphological
changes, potentially representing an important mechanism through-
out animal domestication
At present, only a handful of genes separating wild from domestic
forms have been identified in any domestic animals, including coat
colour variants in MC1R in pig
and a mutation in TSHR likely to affect
seasonal reproduction in chicken
, but to our knowledge in dogs no
genome-wide sequence-based searches have been performed until
now. To identify genomic regions under selection during dog domesti-
cation we performed pooled whole-genome resequencing of dogs and
wolves followed by functional characterization of candidate genes.
Uniquely placed sequence reads from pooled DNA representing
12 wolves of worldwide distribution and 60 dogs from 14 diverse breeds
(Supplementary Table 1) covered 91.6% and 94.6%, respectively, of
the 2,385 megabases (Mb) of autosomal sequence in the CanFam 2.0
genome assembly
. The aligned coverage depth was 29.83for all dog
pools combined and 6.23for the single wolf pool (Supplemen-
tary Table 1 and Supplementary Fig. 1). We identified 3,786,655 putat-
ive single nucleotide polymorphisms (SNPs) in the combined dog and
wolf data, 1,770,909 (46.8%) of which were only segregating in the dog
pools, whereas 140,818 (3.7%) were private to wolves (Supplementary
Table 2). Similarly we detected 506,148 short indels and 26,619 copy-
number variations (CNVs) (Supplementary Files 1 and 2). We were
able to experimentally validate 113 out of 114 tested SNPs (Sup-
plementary Table 3 and Supplementary Discussion, section 1).
To detect signals of strong recent selection we searched the dog
genome for regions with reduced pooled heterozygosity (H
or increased genetic distance to wolf (F
). As evident from the skewed
distribution of heterozygosity scores in dog relative to wolf (Fig. 1a and
Supplementary Fig. 2), a major challenge to this approach is to sepa-
rate true signals of selection from those caused by random fixation of
large genomic regions during the formation of dog breeds
. We alle-
viate this problem by combining sequence data from all dog pools
before selection analyses and require that detected signals span at least
200 kilobases (kb; Methodsand Supplementary Discussion, sections 2
and 3). Given the complex and partly unknown demographic history
of dogs, it is furthermore difficult to assign strict thresholds that dis-
tinguish selection and drift. We propose that the best way to validate
regions detected here is to study genetic data from additional indivi-
duals and provide evidence for functional change associated with
putatively selected regions. Eventually, indications that similar path-
ways changed during independent domestication events may provide
conclusive evidence for selection. Here we Z-transform the autosomal
)) and F
)) distributions (see Supplementary Dis-
cussion, section 4 for an analysis of the X chromosome) and focus
our description of putatively selected regions to those that fall at least
five standard deviations away from the mean (Z(H
),25 and
).5), as these represent the extreme ends of the distributions.
By applying these thresholds we identified 14 regions in the dog
genome with extremely low levels of heterozygosity (average length 5
400 kb, average H
50.036 (range 0.015–0.056), average autosomal
50.331) (Fig. 1c and Supplementary Table 4) and 35 regions
with strongly elevated F
values (average length 5340 kb, average
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 75237 Uppsala, Sweden.
Broad Institute of Massachusetts Institute of Technology and Harvard,
Cambridge, Massachusetts 02139, USA.
¨Wildlife Research Station, Department of Ecology, Swedish University of Agricultural Sciences, 73091 Riddarhyttan, Sweden.
Department of Forestry and
Wildlife Management, Faculty of Applied Ecology and Agricultural Sciences, Hedmark University College, Campus Evenstad, NO-2418 Elverum, Norway.
Department of Wildlife, Fish and Environmental
Studies, Faculty of Forest Sciences, Swedish University of Agricultural Sciences, 901 83 Umea
˚, Sweden.
Science for Life Laboratory, Department of Clinical Sciences, Swedish University of Agricultural
Sciences, 75651 Uppsala, Sweden.
360 | NATURE | VOL 495 | 21 MARCH 2013
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50.734 (range 0.654–0.903), average autosomal F
(Fig. 1b and Supplementary Table 5). All F
regions are characterized
by low levels of heterozygosity in eitherdog or wolf (although all do not
pass the Z(H
),25 threshold), indicating that the two statistics
detect the same events (Methods and Supplementary Discussion,
sections 2 and 3). In total, 36 unique autosomal candidate domestica-
tion regions (CDRs) containing 122 genes were identified by the
two approaches combined (Supplementary Table 6 and Fig. 1b, c).
None of these regions overlaps those of a previous genotype-based
(Supplementary Discussion, section 3), stressing the im-
portance of identifying domestication regions directly by sequencing
or by comprehensively ascertaining SNPs in wild ancestors before
We searched for significantly overrepresented gene ontology terms
among genes in autosomal CDRs and identified 25 categories, repre-
senting several groups of interrelated terms (Table 1 and Supplemen-
tary Table 7), none of which was indicated in a separate analysis of
selection in wolf (Supplementary Discussion, section 8). The most
conspicuous cluster (11 terms) relates to the term ‘nervous system
development’. The eight genes belonging to this category (Supplemen-
tary Tables 7 and 8) include MBP,VWC2,SMO,TLX3,CYFIP1 and
SH3GL2, of which several affect developmental signalling and synaptic
strength and plasticity
. We surveyed published literature and iden-
tified 11 additional CDR genes with central nervous system function
(Supplementary Table 9), adding to a total of 19 CDRs that contain
brain genes. These findings support the hypothesis that selection for
altered behaviour was important during dog domestication and that
mutations affecting developmental genes may underlie these changes
The gene ontology analysis also pinpointstwo genes involved in the
binding of sperm and egg: ZPBP encodes the zona pellucida binding
protein that mediates binding of sperm to the zona pellucida glycopro-
tein layer (ZP) of the egg, and ZP2 codes for one of the proteins that
make up ZP itself. In addition, a CDR on chromosome 6 encompasses
PDILT that also affects binding of sperm to ZP
, altogether indicating
that sperm competition may have been an important evolutionary
force during dog domestication
Overrepresented terms ‘starch metabolic process’, ‘digestion’ and
‘fatty acid metabolism’ include genes involved in starch digestion
(MGAM)andglucoseuptake(SGLT1), as well as a candidate gene for
−8 −4 0 4
μ = 0
σ = 1
−8 −4 0 4
μ = 0
σ = 1
−4 0 4 8
μ = 0
σ = 1
Number of 200-kb windows
Figure 1
Selection analyses identified 36 candidate domestication regions.
a, Distribution of Z-transformed average pooled heterozygosity in dog
) and wolf (Z(H
) respectively, as well as average fixation
index (Z(F
)), for autosomal 200 kb windows (s, standard deviation; m,
average). b, The positive end of the Z(F
) distribution plotted along dog
autosomes 1–38 (chromosomes are separated by colour). A dashed horizontal
line indicates thecut-off (Z.5) used for extracting outliers. c, The negative end
of the Z(H
) distribution plotted along dog autosomes 1–38. A dashed
horizontal line indicates the cut-off (Z,25) used for extracting outliers.
Table 1
Enriched gene ontology terms among CDR genes
Gene ontology term
PFDR value Gene count
Regulation of neuron differentiation 0.005 3 (26)
Multicellular organismal process 0.005 21 (3,822)
Digestion 0.008 4 (95)
Neuron differentiation 0.010 5 (210)
Regulation of molecular function 0.011 8 (671)
Central nervous system development 0.013 5 (235)
Regulation of developmental process 0.013 5 (236)
Generation of neurons 0.013 5 (242)
Nervous system development 0.013 8 (716)
Binding of sperm to zona pellucida 0.015 2 (12)
Sperm–egg recognition 0.015 2 (12)
Neurogenesis 0.015 5 (262)
Cell–cell recognition 0.019 2 (14)
Regulation of catalytic activity 0.020 7 (605)
Regulation of hydrolase activity 0.026 5 (307)
Fatty acid metabolic process 0.031 4 (191)
System development 0.034 11 (1,605)
Regulation of GTPase activity 0.039 4 (211)
Anatomical structure development 0.039 12 (2,005)
Intramembranous ossication 0.039 1 (1)
Quinolinate metabolic process 0.039 1 (1)
Starch metabolic process 0.039 1 (1)
Starch catabolic process 0.039 1 (1)
Glucocorticoid catabolic process 0.039 1 (1)
Cell development 0.039 9 (1,242)
Enriched terms are colour-coded to reflect relatedness in the ontology or functional proximity. Blue,
nervous system development; green, sperm–egg recognition; grey, regulation of molecular function;
orange, digestion. For each term, gene count shows number of genes in CDRsrelative to total number of
annotated genes (in parentheses).
21 MARCH 2013 | VOL 495 | NATURE | 361
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insulin resistance (ACSM2A) that initiates the fatty acid metabolism
A total of 6 CDRs harbour 10 genes with functions related to starch
and fat metabolism (Supplementary Table 10). We propose that gene-
tic variants within these genes may have been selected to aid adapta-
tion from a mainly carnivorous diet to a more starch rich diet during
dog domestication.
The breakdown of starch in dogs proceeds in three stages: (1) starch
is first cleaved to maltose and other oligosaccharides by alpha-amylase
in the intestine; (2) the oligosaccharides are subsequently hydrolysed
by maltase-glucoamylase
, sucrase and isomaltase to form glucose;
and (3) finally, glucose is transported across the plasma membrane
by brush border protein SGLT1
. Here we present evidence for selec-
tion on all three stages of starch digestion during dog domestication.
Whereas humans have acquired amylase activity in the saliva
an ancient duplication of the pancreatic amylase gene, dogs only
express amylase in the pancreas
. In dogs the AMY2B gene, encoding
the alpha-2B-amylase, resides in a 600-kb CDR on chromosome 6 with
) scores of 24.60 and 7.16, respectively(Figs 1 and 2a).
Interestingly, an 8-kb sequence spanning the AMY2B locus showed
a several-fold increase in aligned read depth in dog relative to wolf
(Fig. 2b), suggestive of a copy number change. Formal comparisons of
regional and local pool coverage, and wolf and dog coverage (Methods),
respectively, also suggest a substantial increase in copy numbers in all
dog pools compared to wolf at this locus (Supplementary Discussion,
section 5).
We confirmed this CNV by quantifying AMY2B copy numbers in
136 dogs and 35 wolves (Supplementary Table 11) using real-time
quantitative PCR (qPCR). Whereas all wolves tested carried only
2 copies (2N52), diploid copy numbers in dog ranged from 4 to 30
(P,0.001, Wilcoxon) (Fig. 2c), corresponding to a remarkable
7.4-fold average increase in dog AMY2B copy numbers. To assess
whether this change correspond to a difference in amylase activity,
we first compared AMY2B gene expression in pancreas from dog
(n59) and wolf (n512) and noted a 28-fold higher average expres-
sion in dog (P,0.001, Wilcoxon, Fig. 2d). We then quantified
amylase activity in frozen serum (Fig. 2e) and found a 4.7-fold
higher activity in dog (9.6–18.4mkat l
(n512)) relative to wolf
(1.4–4.3 mkat l
(n513)) (P,0.001, Wilcoxon). Similar results were
obtained in comparisons of a limited number of fresh samples
(Supplementary Tables 12 and 13). The change in AMY2B gene copy
number together with a correlated increase in both expression
level (rho 50.84, P,0.0001, Spearman) (Supplementary Fig. 3) and
enzyme activity (rho 50.63, P,0.01, Spearman) (Supplementary
Fig. 4) indicates that duplications of the alpha-amylase locus conferred
a selective advantage to early dogs by causing an increase in amylase
Maltase-glucoamylase is responsible for the second step in the
breakdown of starch, catalysing the hydrolysis of maltose to glucose
No copy number changes were observed in the MGAM locus so we
decided to study haplotype diversity across the region to facilitate the
identification of causal variants. We genotyped 47 randomly selected
SNPs in 71 dogs representing 38 diverse breeds and 19 wolves of
worldwide distribution (referred to as ‘the reference panel’, Sup-
plementary Table 14). Sixty-eight of the seventy-one dogs tested car-
ried at least one copy of a 124-kb long haplotype spanning the entire
MGAM and a small neighbouring locus encoding the bittertaste medi-
ating taste receptor 2 member 38 (TASR38) (Fig. 3a–c). Whereas none
of the wolves carried the selected haplotype, 55 dogs were homozygous
for it, 13 were heterozygous and only three dogs lacked it (2 West
Highland White Terriers and 1 Chinese Crested Dog). This high
degree of haplotype differentiation between dog and wolf (average
for genotyped SNPs 50.75) indicates that this haplotype may
harbour genetic variation of selective advantage to dogs (Supplemen-
tary Discussion, sections 3 and 6).
We identified several candidate mutations within MGAM that may
have been targeted by selection in this region (Supplementary Table 15).
First a conservative amino acid substitution located in the duplicated
trefoil domain of MGAM (residue 1001) is nearly fixed for isoleucine in
wolf and for valinein dogs. Eleven out of fourteenmammals have valine
at this position, whereas the omnivorous rat, and the insectivorous
hedgehog and short-tailed opossum, carry isoleucine like the wolf
(Supplementary Table 16). Second, another conservative substitution,
methionine to valine, located in the beta sheet of the maltase enzyme
(residue 797), is segregating in wolf but fixed formethionine in dog. The
insectivorous hedgehog and common shrew are the only mammals
without methionine at this evolutionarily conserved position (Sup-
plementary Table 17) and in silico modelling using the SDM-server
indicates that a change from methionine to valine at this residue is
. Third, a fixed two-base-pair deletion in dog disrupts
the stop codon, thereby extending the carboxy-terminal end of dog
Number of individuals
Diploid copy number
Wolf Dog
Relative expression
Amylase activity (μkat l–1)
Wolf Dog
34 40 50 75
49.4 51
Figure 2
Selection for increased amylase activity. a, Pooled heterozygosity,
(blue), and average fixation index,F
(orange), plotted for 200-kb windows
across a chromosome 6 region harbouring AMY2B.b, Heterozygosity,H(blue),
and fixation index, F
(orange), for single SNPs in the selected region. Dog
relative to wolf coverage, rC (green line), indicates increase in AMY2B copy
number in dog. Genes in the region are shown below panel b.c, Histogram
showing the distribution of diploid amylase copy number in wolf (n535)
(blue) and dog (n5136) (red). d, Amylase messenger RNA expressionlevels in
pancreas of wolf (n512) and dog (n59). e, Amylase activity in serum from
wolf (n513) and dog (n512).
362 | NATURE | VOL 495 | 21 MARCH 2013
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MGAM by two aminoacids: asparagineand phenylalanine. In32 mam-
mals studied only herbivores (rabbit, pika, alpaca and cow) and omni-
vores (mouse lemur and rat) share an extension like that seen in dog
(Supplementary Table 18). A fourth candidate mutation in intron 37
affects a predicted binding site for the glucose metabolism regulator
NR4A2 protein
by shifting the wolf sequence away from the canonical
NR4A2-binding motif. Three out of four mammals with the wolf allele
at this site rely heavily on insects or fish for their nutritional require-
ments (Supplementary Table 19).
To decipher whether the candidate mutations act primarily on expres-
sion or protein activity we examined MGAM expression in pancreas
and the resulting enzymatic activity in serum. Dogs showed a ,12-fold
higher expression (P,0.001, Wilcoxon, n
59, n
58) (Fig. 3d)
and a ,twofold increase in maltose to glucose turnover compared to
wolves (average glucose produced in dogs: 0.94 DA
570 nm
n57) and wolves: 0.52 DA
570 nm
(0.44–0.66, n58), P50.0012,
Wilcoxon) (Fig. 3e). Although we cannot rule out that diet-induced
plasticity contributed to this difference
, our results indicate that the
mutation affecting a NR4A2-binding site or another unknown variant
probably affect the expression of MGAM. Selection may thus clearly have
led to increased MGAM expression, but we cannot rule out that the
strong selection affecting this locus may have favoured the accumulation
of protein-coding changes on the same haplotype. Similar scenarios have
been seen for white coat colour in dogs and pigs, where repeated selection
for additional mutations has resulted in an allelic series of white spotting
at the MITF and KIT loci, respectively
Once starch has been digested to glucose it is absorbed through
the luminal plasma membrane of the small intestine by the sodium/
glucose cotransporter 1 (SGLT1)
. To benefit from an increased
capacity to digest starch, dogs would therefore be expected to show a
parallel increase in glucose uptake. A CDR on chromosome 26 (Sup-
plementary Fig. 5a, b) encompasses SGLT1 and a gene (SGLT3) encod-
ing the glucose-sensing sodium/glucose cotransporter 3 protein
characterize the haplotype diversity we genotyped 48 randomly chosen
SNPs across this CDR in the reference panel and identified a 50.5-kb
region, spanning the 39section of SGLT1 as well as the 39end of SGLT3,
that is highly divergent between dog and wolf (Supplementary Fig. 5c).
In this region all dogs tested were carriers of a particular haplotype,
for which 63 were homozygous and eight heterozygous. This con-
trasts to 19 wolves where a single individual carried one copy of the
haplotype. Based on the high haplotype differentiation (average F
for 18 SNPs in 50.5-kb haplotype 50.81) it is likely that SGLT1 and
its 39region represents an additional dog domestication locus.
The 50.5-kb region includes a conservative isoleucine to valine
substitution in SGLT1 (residue 244) that affects a loop facing the
extracellular side of the luminal membrane (Supplementary Table 15).
Heterologous expression analysis
shows that glycosylation at a nearby
site (residue 248) affects glucose transport, indicating that it is possible
that dogs acquired improved glucose uptake as a result of the observed
substitution. In addition, we see only non-significant differences in SGLT1
expression in pancreas of dog (n59) and wolf (n54) (P50.39,
Wilcoxon) (Supplementary Fig. 6), indicating that selection primarily
targeted a structural rather than regulatory mutation in SGLT1.
In conclusion, we have presented evidence that dog domestication
was accompanied by selection at three genes with key roles in starch
digestion: AMY2B,MGAM and SGLT1. Our results show that adapta-
tions that allowed the early ancestorsof modern dogs to thrive on a diet
rich in starch, relative to the carnivorous diet of wolves, constituted a
crucial step in early dog domestication. This may suggest that a change
of ecological niche could have been the driving force behind the
domestication process, and that scavenging in waste dumps near the
increasingly common human settlements during the dawn of the agri-
cultural revolution may have constituted this new niche
. In light of
previous results describing the timing and location of dog domestica-
tion, our findings may suggest that the development of agriculture
catalysed the domestication of dogs.
The results presented here demonstrate a striking case of parallel
evolution whereby the benefits of coping with an increasingly starch-
rich diet during the agricultural revolution caused similar adaptive
responses in dog and human
. This emphasizes how insights from
dog domestication may benefit our understanding of human recent
evolution and disease. Finally, by understanding the genetic basis of
adaptive traits in dogs we have come closer to unlocking the potential
in dog and wolf comparisons to decipher the genetics of behaviour.
Sequencing. We pooled genomic DNA from 12 individuals before mate-pair
library construction and sequencing on the AB SOLiD system, version 3, accord-
ing to standard manufacturer protocols. Sequencing reads were aligned to the
CanFam 2.0 reference sequence using the Bioscope 1.1 software.
Selection analyses. We identified variable sites in data combined from all pools
and required a minimum of three reads supporting an alternative allele to call a
SNP. We used allele countsat variable sites to identify signals of selection in 200-kb
windows using two approaches: for each window we calculated (1) the average
pooled heterozygosity, H
(ref. 10), and (2) the average fixation index, F
between dog and wolf. Putatively selected regions were located by extracting
Wolf Dog
Relative expression
Wolf Dog
MGAM activity
310 20 30 40 50 60
9.2 10.1 11.0
10.09 10.23
<<<<< >>>
Figure 3
Selection is associated with increased maltase activity. a, Pooled
heterozygosity, H
(blue), and average fixation index, F
(orange), plotted for
200-kb windows across a chromosome 16 region harbouring MGAM.
b, Heterozygosity, H(blue), andfixation index, F
(orange), for single SNPs in
the selected region. c, Haplotypes inferred from genotyping of 47 SNPs across
the MGAM locus in 71 dogs and 19 wolves (red and blue colour are major and
minor dog allele, respectively). Genes in the genotyped region are shown below
panel c.d,MGAM mRNA expression levels in pancreas of wolf (n58) and dog
(n59). e, MGAM activity in serum from wolf (n58) and dog (n57).
21 MARCH 2013 | VOL 495 | NATURE | 363
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windows from the extreme tails of the Z-transformed H
and F
distributions by
applying a threshold of 5 standard deviations.
Functional assays. We used multiplex TaqMan assays and SYBR Green real-time
PCR to quantify CNVs and gene expression, respectively. Serum amylase activity
was analysed using an Architect e400 instrument and serum maltase activity was
quantified based on the amount of maltose to glucose turnover.
Full Methods and any associated references are available in the online version of
the paper.
Received 1 July; accepted 11 December 2012.
Published online 23 January 2013.
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hepatic glucose metabolism. Nature Med. 12, 1048–1055 (2006).
26. Mochizuki, K., Honma, K., Shimada, M. & Goda, T. The regulation of jejunal
inductionof the maltase-glucoamylase gene by a high-starch/low-fat diet in mice.
Mol. Nutr. Food Res. 54, 1445–1451 (2010).
27. Andersson, L. Studying phenotypic evolution in domestic animals: a walk in the
footsteps of Charles Darwin. Cold Spring Harb. Symp. Quant. Biol. 74, 319–325
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Natl Acad. Sci. USA 100, 11753–11758 (2003).
29. Hediger, M. A., Mendlein, J., Lee, H. S. & Wright, E. M. Biosynthesis of the cloned
intestinal Na
glucose cotransporter. Biochim. Biophys. Acta 1064, 360–364
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Supplementary Information is available in the online version of the paper.
Acknowledgements We thank Ja
¨rvzoo, Nordens ark and the Canine Biobank at
Uppsala University and the Swedish University of Agricultural Sciences for providing
samples, Uppsala Genomics Platform at SciLifeLab Uppsala for generating the
resequencing data, the UPPNEX platform for assisting with computational
infrastructure for data analysis and the Broad Institute Genomics Platform for
validation genotyping. The project was funded by the SSF, the Swedish Research
Council, the Swedish Research Council Formas, Uppsala University and a EURYI to
K.L.-T.funded by the ESF supportingalso E.A.; K.M. was funded by the HigherEducation
Commission, Pakistan.
Author Contributions K.L.-T. and A
˚.H. designed the study. K.L.-T. and E.A. oversaw the
study. M.-L.A.coordinated and performedthe majority of the samplecollecting and O.L.
and J.M.A. provided samples of critical importance. E.A. performed the SNP detection
and selection analyses; A.R. identified candidate causative mutations and analysed
haplotypes in CDRs; K.M. detected CNVs bioinformatically; M.T.W. performed
phylogenetic analysis and analysed the Canine HD-array data; A.R. performed the
maltase activity assay; M.-L.A. validated CNVs and quantified mRNA expression of
candidate genes; M.P. performed validation SNP genotyping; E.A., A.R., M.-L.A. and
K.L-T. interpreted the data; E.A. and K.L.-T. wrote the paper with input from the other
Author Information Sequence reads are available under the accession number
SRA061854 (NCBI Sequence Read Archive). Reprints and permissions information is
available at The authors declare no competing financial
interests. Readers are welcome to comment on the online version of the paper.
Correspondence and requests for materials should be addressed to E.A.
( and K.L-T. (
364 | NATURE | VOL 495 | 21 MARCH 2013
Macmillan Publishers Limited. All rights reserved
DNA extraction. DNA was extracted from tissue using Qiagen tissue DNA
extraction kits or from EDTA blood using either manual salt precipitation or
the QIASymphony DNA Midikit (Qiagen) on the QIASymphony robot (Qiagen).
Sequencing. We pooled DNA from 12 individuals per pool before mate-pair
library construction and sequencing on the AB SOLiD system, version 3, accord-
ing to standard manufacturer protocols (Applied Biosystems). Sequencing reads
were aligned to the CanFam 2.0 reference sequence using the Bioscope 1.1 soft-
ware. We removed duplicated ( and poorly mapped
reads (mapping quality ,20 in Samtools)
and retained only uniquely mapped
reads for further analyses.
SNP detection. We searched for variable sites in data combined from all pools
(including wolf) to increase sensitivity to rare alleles. We required a minimum of
three reads supporting an alternative allele to call a SNP, and applied a further
filtering step implemented in varFilter (settings: –Q25 –q10 –d3
–D120 –G25–w10 –N2 –l30) to ensure a high callaccuracy that is largely unaffected
by, for example, paralogous sequence variants. We called genotypesfor all SNPs in
all dog pools and the single wolf pool by counting sequencing reads supporting the
reference and variant allele, given a minimum base quality of 20, to estimate allele
frequencies in the dog and wolf populations. A random selection representing
25% of the sequencing reads from pools 4 and 5 were included in this process to
achieve unbiased allele frequency estimates.
Selection analyses. Allele counts and allele frequencies at all identified variable
sites were used to search the dog genome for regions that may have been affected
by selection duringthe early phase of dog domesticationusing two complementary
approaches. First we calculated the average pooled heterozygosity (H
) in 200-kb
windows sliding 100kb at a time, for all five dog pools combined, and in the single
wolf pool separately, following the methodology described in ref. 10. Briefly, this
method sums all minor and major allele counts, respectively, at all variable sites
within a window, and estimates the heterozygosity based on the combined allele
counts for the entire window. The advantage of this method over calculating a
simple arithmeticmean of all single-site heterozygosity estimatesis that it accounts
for variable sequence coverage across the window. To avoid spurious selection
signals we discarded 49 out of 21,927 windows containing fewer than 10 inform-
ative sites from both this and the subsequent F
analysis. We Z-transformed the
resultant distribution of H
scores and extracted putatively selected windows in
the extreme tail of the distribution by applying a Z(H
),25 cut-off.
Second we calculated F
values between dog and wolf for individual SNPs
using a method that adjusts for sample size differences
. We averaged F
across 200-kb windows, sliding 100 kb at a time and Z-transformed the resultant
distribution. Putative selection targets were extracted from the extreme tail of the
distribution by applying a Z(F
).5 cut-off, and attributed to selection in dog if
the corresponding Z(H
, to selection in wolf if Z(H
(three regions), and to selection in both taxa if Z(H
,24 and
Gene ontology analysis. We used the Ensembl gene annotationsto identify genes
residing within regions extending 100kb up- and downstream of CDRs to include
potential effects of regulatory changes on loci at some distance, and to reduce the
risk of excluding the outermostportions of the selected haplotypes by using sliding
windows of fixed size. We tested for enrichment of gene ontology terms (GOa-
human) assigned to the subset of these CDR genes for which human orthology
could be established (79 out of 122) using the GOstat program
Genotyping validation. We designed an iPLEX assay targeting 124 SNPs located
in CDRs showing a high degree of homozygosity or population differentiation. A
total of 71 dogs, representing 38 different breeds, and 19 wolves (Supplementary
Table 14) were genotyped using standard protocols provided by the manufacturer
(Sequenome). Haplotypes were phased using fastPHASE
qPCR CNV detection. We quantified DNA copy number variation using Multi-
plex TaqMan assays containing primers and probes (Supplementary Table 20)
matching both the target and reference sequence (housekeeping gene C7orf28b)
according to the manufacturer’s protocol. All reactions were run in triplicate and
data was analysed using the CopyCaller software (Applied Biosystems). Copy
numbers for each target were normalized to the same wolf to account for inter-
plate variability.
qPCR expression analyses. Pancreatic tissue samples from dogs and wolves
where collected postmortem, stored in RNAlater at 4 uC for 24 h and subsequently
freeze-stored at 280uC. We used TRIzol to isolate RNA from these samples,
followed by complementary DNA synthesis using the Advantage RT for PCR
kit according to the manufacturers’ protocols (Life Technologies and Clontech,
respectively). We designed exonic primers (Supplementary Table 21) and quan-
tified the amount of cDNA using SYBR Green real-time PCR (Applied bio-
sciences) on a 7900HT Fast real time PCR system (Applied Biosystems) and
analysed the data using the qbasePLUS (Biogazelle) software according to the
method. All reactions where run in triplicate and normalized by compari-
sons to housekeeping genes RPL32 and RPL13A.
Amylase activity. Peripheral EDTA and serum blood samples where collected
from dogs and both captive and free-ranging wolves. Serum amylase activity was
analysed at the Clinical Pathology service (Swedish Agricultural University) using
an Architect e400 instrument (Abott Laboratories), except for 8 serum samples
(Supplementary Table 13) which were run on a VetScan instrument (Abaxis).
Maltase activity. Maltase activity was assayed according to the principle outlined
in ref. 35, whereby a known amount of maltose substrate is added to serum and
the resultant glucose produced is measured as the change in absorbance after
five minutes (DA
). We used reagents from the ab83388 Maltose assay kit
(Abcam) and serum sampled as described above. For each individual, glu-
cose residuals were measured in duplicate and maltase assays were performed
in triplicate.
Indel calling. We used Bioscope 1.1 to call small insertions and deletions in each
pool separately. We then combined the results of all pools and extracted a set of
high confident indels by requiring that indels were supported by at least three
sequencing reads.
CNV detection. Four methods were used to detect structural variation in the dog
genome. We searched for deviations in insert size using the large indel tool imple-
mented in Bioscope1.1. We compared the coverage depth between the pooled
samples using CNVseq
and the Fixed deletions method
and finally identified
regions in which the coverage depth deviated from the pool average using
. Methods relying on comparisons of sequence coverage between
pools always used the wolf as reference pool.
Ethics. All animals contributingtissue samples to this study died for other reasons
than participating in this study. All dog samples were taken with the owners
consent. The sampling conformed to the decision of the Swedish Animal
Ethical Committee (no. C62/10) and the Swedish Animal Welfare Agency
31. Li, H. et al. The sequence alignment/map format and SAMtools. Bioinformatics
25, 2078–2079 (2009).
32. Weir, B. S. & Cockerham, C. C. Estimating F-statistics for the analysis of
population-structure. Evolution 38, 1358–1370 (1984).
33. Beissbarth, T. & Speed, T. P. GOstat: find statistically overrepresented Gene
Ontologies within a group of genes. Bioinformatics 20, 1464–1465 (2004).
34. Scheet, P. & Stephens, M. A fast and flexible statistical model for large-scale
population genotype data: applications to inferring missing genotypes and
haplotypic phase. Am. J. Hum. Genet. 78, 629–644 (2006).
35. Dahlqvist, A. Method for assay of intestinal disaccharidases. Anal. Biochem. 7,
18–25 (1964).
36. Xie, C. & Tammi, M. T. CNV-seq, a new method to detect copy number variation
using high-throughput sequencing. BMC Bioinformatics 10, 80 (2009).
37. Abyzov, A., Urban, A. E., Snyder, M. & Gerstein, M. CNVnator: An approach to
discover, genotype, and characterize typical and atypical CNVs from family and
population genome sequencing. Genome Res. 21, 974–984 (2011).
Macmillan Publishers Limited. All rights reserved
... Comparing the genomes of closely related animals that have evolved different specializations offers opportunities to understand how differences in their physiology are attributed to differences on the genomic level. Whether it is epistatic interactions of suites of genes affecting phenotypes (e.g., Chen et al. 2022), changes in gene copy number impacting gene expression, which in turn affects enzyme activity levels (Axelsson et al. 2013;Heras et al. 2020;Perry et al. 2007), or molecular convergence of genes underlying unique phenotypic traits (Protas et al. 2005), genomic evidence of adaptation to environmental variables abound in the comparative genomics literature (Fan et al. 2020;Lamichhaney et al. 2015;Taylor et al. 2021;Yuan et al. 2018). As the nutrient supply organ that interfaces directly with items consumed from the environment, the digestive tract has become an attractive system in which to examine how animals can specialize on specific resources (Brun et al. 2020;Karasov Communicated by Joan Cerdá. ...
... But how does dietary specialization impact an animal's genome? With whole genome sequencing becoming more affordable and genomic analyses becoming more accessible, we are now better equipped to explore genomic adaptations to dietary specializations such as carnivory or herbivory (e.g., Axelsson et al. 2013;Heras et al. 2020;Wang et al. 2015). ...
... Depending on the approach, one can start at the genomic level, find areas of a genome that may be under selection, and then scale up to discern what traits are impacted by the molecular changes identified (Axelsson et al. 2013;Yuan et al. 2018). Conversely, one can take a well-known system with well-studied physiological and biochemical processes and dig down to the genetic level to identify the underpinnings of specific phenotypes. ...
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Digestion is driven by digestive enzymes and digestive enzyme gene copy number can provide insights on the genomic underpinnings of dietary specialization. The "Adaptive Modulation Hypothesis" (AMH) proposes that digestive enzyme activity, which increases with increased gene copy number, should correlate with substrate quantity in the diet. To test the AMH and reveal some of the genetics of herbivory vs carnivory, we sequenced, assembled, and annotated the genome of Anoplarchus purpurescens, a carnivorous prickleback fish in the family Stichaeidae, and compared the gene copy number for key digestive enzymes to that of Cebidichthys violaceus, a herbivorous fish from the same family. A highly contiguous genome assembly of high quality (N50 = 10.6 Mb) was produced for A. purpurescens, using combined long-read and short-read technology, with an estimated 33,842 protein-coding genes. The digestive enzymes that we examined include pancreatic α-amylase, carboxyl ester lipase, alanyl aminopeptidase, trypsin, and chymotrypsin. Anoplarchus purpurescens had fewer copies of pancreatic α-amylase (carbohydrate digestion) than C. violaceus (1 vs. 3 copies). Moreover, A. purpurescens had one fewer copy of carboxyl ester lipase (plant lipid digestion) than C. violaceus (4 vs. 5). We observed an expansion in copy number for several protein digestion genes in A. purpurescens compared to C. violaceus, including trypsin (5 vs. 3) and total aminopeptidases (6 vs. 5). Collectively, these genomic differences coincide with measured digestive enzyme activities (phenotypes) in the two species and they support the AMH. Moreover, this genomic resource is now available to better understand fish biology and dietary specialization.
... Studies [12][13][14] describe the structure, feeding pattern and the biology of Ticks. While studies [15][16][17][18] describe the structure, feeding pattern and the biology of dogs. ...
... Research such as those conducted studies [12][13][14] investigate the structure, feeding patterns, and biology of ticks, while others [15][16][17][18] delve into the same aspects for dogs. ...
... This move is facilitated by progress in computer-aided identification of structural variants based on genome-wide sequencing (Ionita-Laza et al., 2009;Teo et al., 2012). Arguments for the role of structural variants in obesity traits can be found in the discussions on the relationship between copy number variation (CNV) in the AMY gene and process of domestication (Axelsson et al., 2013). The first clue that structural variants in genes from the AMY family are associated with obesity was found in humans, where some data show correlation between the copy number of the AMY1 gene, coding for pancreatic amylase, and body mass in children (Mejía-Benítez et al., 2015;León-Mimila et al., 2018), as well as Type 2 diabetes (Liu et al., 2020). ...
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Although obesity in the domestic dog ( Canis lupus familiaris) is known to decrease well-being and shorten lifespan, the genetic risk variants associated with canine obesity remain largely unknown. In our study, which focused on the obesity-prone Labrador Retriever breed, we conducted a genome-wide analysis to identify structural variants linked to body weight and obesity. Obesity status was based on a 5-point body condition score (BCS) and the obese dog group included all dogs with a BCS of 5, along with dogs with the highest body weight within the BCS 4 group. Data from whole-gene sequencing of fifty dogs, including 28 obese dogs, were bioinformatically analyzed to identify potential structural variants that varied in frequency between obese and healthy dogs. The seven most promising variants were further analyzed by droplet digital PCR in a group of 110 dogs, including 63 obese. Our statistical evidence suggests that common structural mutations in or near six genes, specifically ALPL , KCTD8 , SGSM1 , SLC12A6 , RYR3 , and VPS26C , may contribute to the variability observed in body weight and body condition scores among Labrador Retriever dogs. These findings emphasize the need for additional research to validate the associations and explore the specific functions of these genes in relation to canine obesity.
... Globally, more than 400 dog breeds were registered in these associations (10). The history of domesticated dog in China was over 10,000 years (11)(12)(13)(14)(15) and more than 50 breeds with stable genetic characteristic were retained after long time artificial selection, such as ancient Guangdong Shapi dogs, Thin dogs, and Tibetan Mastiff. Chinese indigenous dogs have markedly difference from their ancestor gray wolves, especially their morphological characteristics (16). ...
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The significant morphological differences and abundant germplasm resources of Chinese indigenous dog breeds can be attributed to the diverse geographical environment, including plateaus, mountains, and a long history of raising dogs. The combination of both natural and artificial selection during the past several thousand years has led to hundreds of dog breeds with distinct morphological traits and environmental adaptations. China is one of the earliest countries to domesticate dogs and there are more than 50 ancient indigenous dog breeds. In this study, the run of homozygosity (ROH) and proportion of the autosomal genome covered by ROHs ( F ROH ) were calculated for 10 dog breeds that are the most representative Chinese indigenous dogs based on 170K SNP microarray. The results of F ROH showed that the Chuandong hound dogs (HCSSC) have the highest level of inbreeding among the tested breeds. The inbreeding in HCSSC occurred more recently than the Liangshan dogs (SCLSQ) dogs because of more numbers of long ROHs in HCSSC dogs, and the former also have higher inbreeding degree. In addition, there are significant differences in the inbreeding degree among different subpopulations of the same breed, such as the Thin dogs from Shaanxi and Shandong province. To explore genome-wide selection signatures among different breeds, including coat color, ear shape, and altitude adaptability, we performed genome selection analyses of F ST and cross population extended haplotype homozygosity (XP-EHH). For the coat color, the F ST analysis between Xiasi dogs (XSGZ) and HCSSC dogs was performed and identified multiple genes involved in coat color, hair follicle, and bone development, including MC1R , KITLG , SOX5 , RSPO2 , and TBX15 . For the plateau adaptability, we performed F ST and XP-EHH analyses between dogs from Tibet (Tibetan Mastiffs and Nyingchi dogs) and plain regions (Guangxi Biwei dogs GXBWQ and Guandong Sharpei dogs). The results showed the EPAS1 gene in dogs from Tibet undergo strong selection. Multiple genes identified for selection signals based on different usage of dogs. Furthermore, the results of ear shape analyses showed that MSRB3 was likely to be the main gene causing the drop ear of domestic dogs. Our study provides new insights into further understanding of Chinese indigenous dogs.
... Both dogs and wolves fall within the family Canidae, order Carnivora (2), and are considered omnivores or facultative carnivores based on their feeding strategies and gastrointestinal anatomy and physiology (3). Though the diets of free-roaming wolves and dogs are characterised by intake of prey(4), the domestic dog adapted to consume diet richer in plant materials (5), and show some preference for starch as a dietary energy source (6). Most commercial dog foods contain animal ingredients; indeed, the pet food industry relies heavily on by-products from the slaughter of animals for human consumption (7,8). ...
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Dogs are considered omnivores based on their evolution, consuming diets that include animal tissue. Few feeding trials evaluating the nutritional suitability of exclusively plant-based (vegan) diets in dogs have been published, and the efficacy of vitamin D2 in maintaining canine serum vitamin D levels has not been clearly determined. A blinded dietary trial included 61 healthy desexed adult dogs: 31 fed an experimental extruded vegan diet (PLANT) and 30 fed a commercial extruded meat-based diet (MEAT) for three months. Dogs were screened via veterinary examination and routine laboratory analyses prior to enrolment in the study, at baseline and exit timepoints. Body composition was measured by dual-energy x-ray absorptiometry and blood was collected for vitamin D profiling. All dogs maintained health parameters, body weight and composition throughout the study. Dogs maintained on PLANT demonstrated a significant reduction in platelet count, creatinine, blood urea nitrogen and cholesterol, though values remained within normal reference ranges. Dogs fed PLANT also demonstrated a shift from vitamin D3 to vitamin D2 metabolites, though total vitamin D analogue levels were unchanged, with the exception of 24,25-dihydroxyvitamin D. Bone mineral content and density did not differ from baseline values. Health status was maintained in dogs fed PLANT and vitamin D2 appeared efficacious in maintaining serum total vitamin D concentrations and bone mineralization. Findings support the hypothesis that PLANT was comparable to MEAT for maintenance of healthy adult dogs for at least three months and identified areas where further research is warranted to elucidate the potential risks and benefits of exclusively plant-based vegan diets.
... Las distintas teorías sobre las causas que están detrás o que impulsaron este proceso de domesticación van desde una asociación interesada para aprovechar los recursos derivados de la caza, la cría de lobos para usarlos en ella y para guardar los lugares de habitación, a la presencia de un gen en los cánidos, que en seres humanos se asocia al síndrome de Williams-Beuren, que se manifestaría en una hipersociabilidad por parte de algunos ejemplares, lo que facilitaría su integración en ambientes humanos (VonHoldt et al. 2017), pasando por la modificación genética del perro o vinculada al metabolismo del almidón en contextos más avanzados, pertenecientes ya a sociedades agrícolas (Axelsson et al. 2013). Aunque hay evidencias del control humano en la alimentación de estos cánidos, es evidente que el proceso evolutivo para la aparición del Canis familiaris debió comenzar mucho antes de las primeras sociedades agrícolas, porque la presencia del perro en tumbas o formando parte de rituales en contextos neolíticos es ya constante y está documentada en Europa y Próximo Oriente y, por otra parte, la llegada al continente americano de los primeros perros es anterior a la aparición de la agricultura, lo que implica que la transformación del lobo en perro tuvo que producirse con anterioridad. ...
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Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.
The range of aggressive behaviors observed in humans cannot be studied in a single animal model, but a spectrum of animal models can facilitate an understanding of the genetic regulation of aggression. This chapter discusses recent discoveries in the genetics of aggression in rodents, canids, and primates. Rodents, often used to study intermale aggression, provide advantages for functional studies using gene modification techniques. Dramatic changes in aggressive behavior, which took place during dog and fox domestication, allow the investigation of a wider array of aggressive behaviors. Finally, studies of individual differences in the behavior of rhesus monkeys and other primates provide insight into developmental aspects of aggression and gene–environment interactions. Although studies of human social behavior using animal models present challenges, a spectrum of such models, each of which provides its own unique information, can work synergistically to yield robust insights into human aggressive behavior.
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Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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THREE canid finds from the Natufian in the northern Israeli sites of Bin Mallaha (Eynan) and Hayonim terrace indicate a special man–animal relationship. These consist of a diminutive carnassial and mandible, and a wolf or dog puppy skeleton buried with a human. The finding of a puppy skeleton in such close association with man is of particular significance as an indication of a close relationship between man and dog.
Strong evidence indicates that regulated mRNA translation in neuronal dendrites underlies synaptic plasticity and brain development. The fragile X mental retardation protein (FMRP) is involved in this process; here, we show that it acts by inhibiting translation initiation. A binding partner of FMRP, CYFIP1/Sra1, directly binds the translation initiation factor eIF4E through a domain that is structurally related to those present in 4E-BP translational inhibitors. Brain cytoplasmic RNA 1 (BC1), another FMRP binding partner, increases the affinity of FMRP for the CYFIP1-eIF4E complex in the brain. Levels of proteins encoded by known FMRP target mRNAs are increased upon reduction of CYFIP1 in neurons. Translational repression is regulated in an activity-dependent manner because BDNF or DHPG stimulation of neurons causes CYFIP1 to dissociate from eIF4E at synapses, thereby resulting in protein synthesis. Thus, the translational repression activity of FMRP in the brain is mediated, at least in part, by CYFIP1.
1.1. A procedure is described for assay of disaccharidase activities in extracts of intestinal mucosa, using a Tris-glucose oxidase reagent for assay of the glucose liberated from the substrate. The incubation conditions are discussed.2.2. A unit for disaccharidase activity is defined that is in accord with recommendations made by the Joint Sub-Commission on Clinical Enzyme Units of the International Unions of Biochemistry and of Pure and Applied Chemistry.
Experiments indicate that selection against aggression in mammals can have multiple effects on their morphology, physiology, behaviour and psychology, and that these results resemble a syndrome of changes observed in domestic animals. We hypothesize that selection against aggression in some wild species can operate in a similar way. Here we consider the bonobo, Pan paniscus, as a candidate for having experienced this 'self-domestication' process. We first detail the changes typically seen in domesticated species including shifts in development. We then show that bonobos show less severe forms of aggression than chimpanzees, Pan troglodytes, and suggest that this difference evolved because of relaxed feeding competition. We next review evidence that phenotypic differences in morphology and behaviour between bonobos and chimpanzees are analogous to differences between domesticates and their wild ancestors. We then synthesize the first set of a priori experimental tests of the self-domestication hypothesis comparing the psychology of bonobos and chimpanzees. Again, bonobo traits echo those of domesticates, including juvenilized patterns of development. We conclude that the self-domestication hypothesis provides a plausible account of the origin of numerous differences between bonobos and chimpanzees, and note that many of these appear to have arisen as incidental by-products rather than adaptations. These results raise the possibility that self-domestication has been a widespread process in mammalian evolution, and suggest the need for research into the regulatory genes responsible for shifts in developmental trajectories in species that have undergone selection against aggression.