Recombinational Landscape and Population Genomics of Caenorhabditis elegans

Abstract

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.

Author Summary

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.