Recombinational Landscape and Population Genomics of
Matthew V. Rockman1,2,3,4*, Leonid Kruglyak1,2,5*
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America, 2Department of Ecology and Evolutionary Biology,
Princeton University, Princeton, New Jersey, United States of America, 3Department of Biology, New York University, New York, New York, United States of America,
4Center for Genomics and Systems Biology, New York University, New York, New York, United States of America, 5Howard Hughes Medical Institute, Chevy Chase,
Maryland, United States of America
Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical
parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We
performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C.
elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic
patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we
show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome,
spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the
genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C.
elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that
some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the
remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The
population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the
estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low,
corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate
and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of
genomic similarity, permit association mapping in wild C. elegans strains.
Citation: Rockman MV, Kruglyak L (2009) Recombinational Landscape and Population Genomics of Caenorhabditis elegans. PLoS Genet 5(3): e1000419.
Editor: Molly Przeworski, University of Chicago, United States of America
Received November 20, 2008; Accepted February 12, 2009; Published March 13, 2009
Copyright: ? 2009 Rockman, Kruglyak. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: We are supported by the NIH (R01 HG004321), by a James S. McDonnell Foundation Centennial Fellowship, a Jane Coffin Childs Fellowship, and New
York University start-up funds. LK is an Investigator of the HHMI. The funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: email@example.com (MVR); firstname.lastname@example.org (LK)
The allelic variants that underlie heritable phenotypic variation
are distributed along chromosomes. Their distribution is shaped
by the machinery of meiosis within individuals and by mutation,
selection, and drift among them. To discover the genetic basis of
complex traits, and to understand the evolutionary dynamics that
shape this genetic architecture, we must characterize empirical
patterns of linkage and linkage disequilibrium. We have
undertaken this task in the nematode C. elegans.
Mapping of thousands of mutants to the genome and molecular
studies of meiotic machinery have provided a view of the large-
scale landscape of the C. elegans recombination map. The
chromosomes exhibit nearly complete crossover interference ,
such that each chromosome experiences one crossover per meiosis
and has a genetic length of 50 cM . Accumulated data from
thousands of two- and three-point mapping crosses and small-scale
SNP-based analyses have demonstrated a general pattern of large,
nearly constant-rate domains on the autosomes, with high
recombination in chromosome arms and low recombination in
chromosome centers. Despite strong global regulation of crossover
number, many details remain unclear, including the locations of
the domain boundaries, the occurrence of fine-scale variation
within domains, and the existence of domain structure on the X
chromosome. Moreover, evidence for the genetic control of
crossover number and position [1–4] leaves open the possibility
that segregating variants may influence recombination patterns in
experimental crosses of natural isolates. Because recombination
patterns have been studied only on broad scales in individual
crosses, involving fewer than two dozen markers per chromosome,
dense characterization of a massive cross promises to clarify the
C. elegans is one of the most exhaustively studied of all species
with respect to developmental, behavioral, and physiological
genomics, but studies of its population biology have lagged.
Although natural genetic variation has been a source of alleles for
genetic analysis in C. elegans since long before the system became a
model , the widely accepted notion that worms exhibit little
variation has discouraged investigations of their diversity. The
difficulty of collecting C. elegans from the wild has compounded the
problem. Nevertheless, recent work has revealed abundant
heritable phenotypic variation among wild C. elegans strains [6–
PLoS Genetics | www.plosgenetics.org1March 2009 | Volume 5 | Issue 3 | e1000419
20] and has begun to reveal the ecological context for this species
[16,17,21–25]. C. elegans geneticists have exploited this variation to
map quantitative trait loci [26–37], and in a handful of cases to
identify the causal mutations underlying phenotypic variation (in
genes npr-1, mab-23, tra-3, zeel-1, plg-1, and scd-2 [10,30,38–43]).
In parallel, studies of variation at molecular markers have begun
to provide an account of the distribution of genetic variation
within and among localities and across genomic regions
[6,7,23,24,40,41,43–60]. These studies have shown that the
species exhibits substantially lower levels of polymorphism and
higher levels of linkage disequilibrium than other model systems,
even those, like Arabidopsis thaliana, that share with C. elegans a
primarily selfing mating system. The empirical pattern of linkage
disequilibrium may result as much from selection against
recombinant genotypes as from attributes of population biology
such as population size and outcrossing rate [24,61]. A genome-
wide assessment of linkage disequilibrium is required to determine
whether natural isolates of C. elegans will be useful for mapping loci
We generated and genetically characterized a recombinant
inbred advanced intercross population to gain insights into the
recombination map in C. elegans, and we characterized a large
panel of wild strains to characterize linkage disequilibrium. The
data on recombination in the lab and in the wild reveal the role of
population genomic processes in shaping genotypic diversity in C.
elegans, and they lay the groundwork for rapid discovery of the
genes underlying phenotypic variation.
Patterns of Recombination in Recombinant Inbred
Advanced Intercross Lines
We genotyped 1454 nuclear SNP markers in 236 recombinant
inbred advanced intercross lines (RIAILs). These lines represent
the terminal generation of a 20-generation pedigree founded by
reciprocal crosses between the laboratory wild type strain N2
(Bristol) and the Hawaiian isolate CB4856. The pedigree includes
ten generations of intercrossing (random pair mating with equal
contributions of each pair to succeeding generations ) followed
by 10 generations of selfing.
The SNP markers span 98.6% of the physical length of the
chromosomes (Table S1). The median spacing is 61,160 bp, and
80% of intervals are shorter than 100 kb. Only 35 marker intervals
(2.4%) are greater than 200 kb. The RIAILs contain 3,629
breakpoints in 772 marker intervals; some breakpoints may be
identical by descent because of the shared ancestry during the
intercrossing phase of RIAIL construction. An estimate of the
mapping resolution of the panel, based on the distances between
intervals containing breakpoints, yields a median bin size of 98 kb.
Because larger bins contain more of the genome than smaller bins,
the expected size of a bin in which a uniformly distributed QTL
will fall is 225 kb.
The RIAILs exhibit a genetic map length of 1588 cM, a 5.3-
fold expansion of the 300 cM F2 genetic map. The realized
expansion is 93% of the expected 5.7-fold map expansion, a
difference attributable, at least in part, to the action of selection
during the construction of the lines.
Although selection and drift may alter the relationship between
recombination fraction and meiotic recombination rate [63,64],
the observed recombination fractions are qualitatively informative
about global patterns of recombination rate variation across C.
elegans chromosomes. The genetic maps for the six C. elegans
chromosomes are similar to one another and exhibit five distinct
domains: two tips with effectively zero recombination, two high
recombination arms, and a low recombination center, consistent
with the pattern observed in classical two- and three-point
mapping crosses . These domains are evident in Marey maps
, which show genetic position as a function of physical position
(Figure 1; Table 1). As the recombination rate within each domain
Figure 1. Recombination rate domains. Marey maps for each
chromosome show genetic position of each marker (black points) as a
function of physical position. Genetic position is measured in
centiMorgans as defined on the recombinant inbred advanced
intercross line population; these are not meiotic distances. Gray lines
show the fits of segmented linear regressions, which estimate the
boundaries of the recombination domains and their relative recombi-
nation rates. The shaded boxes above each plot show the genetically
defined positions of the pairing centers .
C. elegans is a model system for diverse fields of biology,
but its ability to serve as a model for quantitative trait
gene mapping depends on its recombination rate in the
laboratory and in nature. The latter is a function of how
worms mate and migrate in the wild. We examined the
patterns of recombination in a population that we put
through thousands of meioses in the laboratory and in a
collection of strains isolated from nature. The data suggest
that meiotic recombination rate is highly regular in worms,
with discrete domains whose boundaries we identify. The
pattern in natural strains suggests that population
structure, population size, outcrossing rate, and selection
combine to suppress the overall effects of recombination.
Moreover, some ‘‘wild’’ strains appear to be laboratory
contaminants. Nevertheless, the history of recombination
in wild worms is sufficient to permit correlations between
genotype and phenotype to pinpoint the loci responsible
for phenotypic variation.
Linkage and LD in C. elegans
PLoS Genetics | www.plosgenetics.org2March 2009 | Volume 5 | Issue 3 | e1000419
is relatively constant, we used a segmented linear regression to
identify the boundaries between the domains.
The central domain of each autosome occupies roughly half the
chromosome’s length, despite the very different lengths of the
chromosomes (Table 1). For example, the center of chromosome
V is 10.7 Mb, 51% of the chromosome length, while the center of
chromosome III is 6.6 Mb, 48% of that chromosome’s length.
Because all the centers have very similar rates of recombination
per base pair (Table 1), their different physical lengths mean that
the amount of recombination in each center (its genetic length)
varies with total chromosome length. The constraint of one
breakpoint per chromosome then requires that the amount of
recombination in the arms of each chromosome varies inversely
with chromosome length; shorter chromosomes have a larger
fraction of their recombination events in their arms, and the
physical sizes of the arms explain much of the variation among
arms in recombination rates (r2=0.51, p=0.009). Nevertheless,
the arms are heterogeneous in relative and absolute length and
recombination rate, and the central domains are not perfectly
centered on the chromosomes, consistent with the finding of
Barnes et al. . Most notably, the left arm of chromosome IV
has a relative recombination rate more than twice that of the right
arm, though they differ in size by only 15% (Figure 1; Table 1).
Inspection of the Marey maps suggests that there may be
additional rate variation within the defined domains. To
determine whether such variation is expected in the case of
constant-rate domains, we simulated chromosomes along the
RIAIL pedigree with discrete, constant-rate recombination
domains, and we recorded the simulated genotypes at the same
marker intervals as our actual genotype data. The simulated
chromosomes exhibit patterns of variation within the discrete rate
domains qualitatively similar to the observed data, preventing us
from placing confidence in the fine-scale patterns in the data
(Figure 2A). Nevertheless, the fine-scale variation observed in our
data is largely concordant with that present in genetic maps
derived from independent two- and three-point mapping crosses
with classic visible markers (Figure S1), compiled in WormBase
. The general concordance between our map, derived from
meioses at 25uC, and the WormBase map, which comes from
crosses performed at various temperatures but primarily at 20uC,
does not support the notion that the distribution of crossovers is
strongly temperature dependent .
In our data, each chromosome has one very sharp center-arm
boundary and one that is less sharp, and boundaries exhibit the
identical pattern in the classical maps. In five of the six
chromosomes, the less-sharp boundary is on the side of the
chromosome that holds the pairing center  (Figure 1). The
exception is chromosome III.
We find two points of disagreement between our results and
previous discussion of recombination maps in C. elegans. First, the
X chromosome clearly possesses domain structure similar to that
of the autosomes (Figure 1), contrary to inferences from sparser
data. The major distinguishing feature of the X-chromosome
center is its relative size, 36% of the chromosome length, which is
substantially less than the 47–52% on the autosomes. Second, we
find that the chromosome tips have extremely low recombination
rates; the terminal domain of each chromosome end is a region of
Table 1. Chromosomal Domains.
Chr left tip left arm centerright arm right tip
I Size (kb)527 33317182 3835197
Size (%) 3.5 22.147.7 25.41.3
Right end (kb) 5273,858 11,04014,875 15,072
Ratea(cM/Mb)0 3.43 1.346.780
IISize (kb) 306 457371412589670
Size (%)2.0 29.946.7 16.94.4
Right end (kb) 3064,87912,02014,609 15,279
IIISize (kb) 494 3228 66182877567
Right end (kb)4943,72210,34013,21713,784
Size (%)4.118.2 51.921.4 4.5
Right end (kb)7203,89612,97016,71217,494
VSize (kb) 6435254106533787583
Size (%)220.127.116.11 18.12.8
Right end (kb)6435,89716,55020,33720,920
XSize (kb) 5725565634339371302
Size (%)3.2 31.435.822.27.3
Right end (kb)5726,13712,48016,41717,719
aRates are derived from the slopes of the segmented linear fits, scaled to yield a
total genetic length of 50 cM for each chromosome.
Figure 2. Simulated chromosomes. (A) The Marey maps for actual
chromosome III data (black) and 10 chromosome III datasets simulated
with discrete, constant-rate recombination domains (colors) show that
variation within domains and indistinct boundaries between domains
are expected. (B) The observed genetic length of chromosome III is
smaller than expected. The histogram shows the lengths of 1000
chromosome III datasets simulated assuming one crossover per meiosis.
Linkage and LD in C. elegans
PLoS Genetics | www.plosgenetics.org3March 2009 | Volume 5 | Issue 3 | e1000419
Found at: doi:10.1371/journal.pgen.1000419.s008 (0.03 MB
expected positions, and map-based positions.
Found at: doi:10.1371/journal.pgen.1000419.s009 (0.02 MB
Misplaced SNP markers. Illumina oligo sequences,
We thank Marie-Anne Fe ´lix, Antoine Barrie `re, and the Caenorhabditis
Genetics Center, funded by the NIH National Center for Research
Resources, for strains. We thank Semyon Kruglyak for designing the
genotyping assays and Connie Zhao for performing the genotyping. We
thank Joshua Shapiro, Rajarshi Ghosh, Hannah Seidel, Daniel Pollard,
Marie-Anne Fe ´lix, and participants in the Kavli Institute for Theoretical
Physics program on Population Genetics and Genomics (supported by
National Science Foundation Grant PHY05-51164) for valuable sugges-
Conceived and designed the experiments: MVR LK. Performed the
experiments: MVR. Analyzed the data: MVR. Wrote the paper: MVR.
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Linkage and LD in C. elegans
PLoS Genetics | www.plosgenetics.org 16March 2009 | Volume 5 | Issue 3 | e1000419