Rockman MV, Kruglyak L. Recombinational landscape and population genomics of Caenorhabditis elegans. PLoS Genet 5: e1000419

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
PLoS Genetics (Impact Factor: 7.53). 04/2009; 5(3):e1000419. DOI: 10.1371/journal.pgen.1000419
Source: PubMed


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.

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    • "Natural genetic variation is also found in resistance toward different pathogens such as Bacillus thuringiensis (Schulenburg and M€ uller 2004; Volkers et al. 2013) or viruses (Ashe et al. 2013), suggesting that these may exert high selective pressure in nature. Similar variation among natural isolates has also been identified for several other life-history traits, for example, different environmentally dependent influences on fecundity (Harvey and Viney 2007; Diaz and Viney 2014), generation and developmental time (Volkers et al. 2013), copulatory plug formation (Hodgkin and Doniach 1997; Rockman and Kruglyak 2009), dauer formation (Green et al. 2013), or male frequency and mating ability (Hodgkin and Doniach 1997; Teot onio et al. 2006; Wegewitz et al. 2008; Anderson et al. 2010), indicating that these may similarly be subject to natural selection. To date, however , the number of populations with sufficiently large sample size, repeated sampling time points, collected substrate types, and considered environmental parameters is still comparatively small, limiting the generality of the current findings. "
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    ABSTRACT: The nematode Caenorhabditis elegans is a central laboratory model system in almost all biological disciplines, yet its natural life history and population biology are largely unexplored. Such information is essential for in-depth understanding of the nematode's biology because its natural ecology provides the context, in which its traits and the underlying molecular mechanisms evolved. We characterized natural phenotypic and genetic variation among North German C. elegans isolates. We used the unique opportunity to compare samples collected 10 years apart from the same compost heap and additionally included recent samples for this and a second site, collected across a 1.5-year period. Our analysis revealed significant population genetic differentiation between locations, across the 10-year time period, but for only one location a trend across the shorter time frame. Significant variation was similarly found for phenotypic traits of likely importance in nature, such as choice behavior and population growth in the presence of pathogens or naturally associated bacteria. Phenotypic variation was significantly influenced by C. elegans genotype, time of isolation, and sampling site. The here studied C. elegans isolates may provide a valuable, genetically variable resource for future dissection of naturally relevant gene functions.
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    • "We characterized 66 components of the escape response (the same as those used for association mapping above) in 138 RIAILs, made from Bristol and Hawaii parent strains (Rockman and Kruglyak 2009). We found substantial phenotypic variation in different behavioral components among the RIAILs. "
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    ABSTRACT: Individuals within a species vary in their responses to a wide range of stimuli, partly as a result of differences in their genetic makeup. Relatively little is known about the genetic and neuronal mechanisms contributing to diversity of behavior in natural populations. By studying intra-species variation in innate avoidance behavior to thermal stimuli in the nematode Caenorhabditis elegans, we uncovered genetic principles of how different components of a behavioral response can be altered in nature to generate behavioral diversity. Using a thermal pulse assay, we uncovered heritable variation in responses to a transient temperature increase. Quantitative trait locus mapping revealed that separate components of this response were controlled by distinct genomic loci. The loci we identified contributed to variation in components of thermal pulse avoidance behavior in an additive fashion. Our results show that the escape behavior induced by thermal stimuli is composed of simpler behavioral components that are influenced by at least six distinct genetic loci. The loci that decouple components of the escape behavior reveal a genetic system that allows independent modification of behavioral parameters. Our work sets the foundation for future studies of evolution of innate behaviors at the molecular and neuronal level. Copyright © 2015, The Genetics Society of America.
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    • "Next, we looked at the distribution of the SNVs and indels across and within the chromosomes. C. elegans chromosomes have a distinctive organization, with the outer 20– 30% of each chromosome (the arms) exhibiting a higher rate of recombination and a higher fraction of repeated sequences (Barnes et al. 1995; Rockman and Kruglyak 2009). They also contain the bulk of genes for large, rapidly evolving gene families. "
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    ABSTRACT: The Hawaiian strain (CB4856) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. The CB4856 genome when compared against the N2 reference has 327,050 single nucleotide variants (SNVs) and 79,529 insertion-deletion events (indels) that result in a total of 3.3 megabasepairs (Mb) of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 not present in N2. As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, that have a greatly elevated SNV density, ranging from 2% to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes. Copyright © 2015, The Genetics Society of America.
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