Recombinational landscape and population genomics of Caenorhabditis elegans.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
PLoS Genetics (Impact Factor: 8.17). 04/2009; 5(3):e1000419. DOI: 10.1371/journal.pgen.1000419
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Micro-RNA (miRNA) genes encode abundant small regulatory RNAs that play key roles during development and in homeostasis by fine-tuning and buffering gene expression. This layer of regulatory control over transcriptional networks is preserved by selection across deep evolutionary time, yet selection pressures on individual miRNA genes in contemporary populations remain poorly characterized in any organism. Here, we quantify nucleotide variability for 129 miRNAs in the genome of the nematode Caenorhabditis remanei to understand the micro-evolution of this important class of regulatory genes. Our analysis of three population samples and C. remanei's sister species revealed ongoing natural selection that constrains evolution of all sequence domains within miRNA hairpins. We also show that new miRNAs evolve faster than older miRNAs but that selection nevertheless favors their persistence. Despite the ongoing importance of purging of new mutations, we discover a trove of >400 natural miRNA sequence variants that include SNPs in seed motifs, indels that ablate miRNA functional domains, and origination of new miRNAs by duplication. Moreover, we demonstrate substantial nucleotide divergence of pre-miRNA hairpin alleles between populations and sister species. These findings from the first global survey of miRNA microevolution in Caenorhabditis support the idea that changes in gene expression, mediated through divergence in miRNA regulation, can contribute to phenotypic novelty and adaptation to specific environments in the present day as well as the distant past.
    Genome Biology and Evolution 10/2014; · 4.53 Impact Factor
  • Source
    Bulletin of Marine Science -Miami- 01/2014; 90(1):79-122. · 1.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Experimental evolution studies, coupled with new advances in DNA sequencing technology, have become a powerful tool for exploring how populations respond to selection at the genomic level. Recent experiments in microbes have typically found evidence for multiple novel mutations, which are usually fixed. In contrast, in animal model systems, evolutionary responses seem to involve more modest changes in the frequencies of pre-existing alleles, probably because these populations outcross and are usually initialized with higher levels of standing variation. In this experiment, I used whole-genome re-sequencing to estimate allele frequencies and look for novel substitutions in experimentally evolved populations of Caenorhabditis elegans. These populations were founded with a fixed pair of deleterious mutations introgressed into multiple wild genetic backgrounds, and allowed to evolve for fifty generations with a mixed mating system. There is evidence for some recombination between ancestral haplotypes, but selective sweeps seem to have resulted in the fixation of large chromosomal segments throughout most of the genome. In addition, a few new mutations were detected. Simulations suggest that strong selection and low outcrossing rates are likely explanations for the observed outcomes, consistent with earlier work showing large fitness increases in these populations over fifty generations. These results also show clear parallels to population genetic patterns in C. elegans in nature: recent selective sweeps, high linkage disequilibrium, and low effective recombination rates. Thus, the genomic consequences of selection depend heavily on the biology of the organism in question, including its mating system and levels of genetic variation.
    G3-Genes Genomes Genetics 07/2014; · 2.51 Impact Factor

Preview (2 Sources)

Available from