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: 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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    • "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.
    Genetics 05/2015; 200(3). DOI:10.1534/genetics.115.175950 · 5.96 Impact Factor
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    • "The RIAILs used in this study have 1454 genotyped nuclear SNP markers span 98.6% of the physical length of the chromosomes [27]. We used these SNPs to calculate MAC for each RIAIL and found a great variation in MAC among the RIAILs (MAC from ~0.2 to ~0.7) (Supplementary Table S1). "
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    ABSTRACT: We studied the collective effects of single nucleotide polymorphisms (SNPs) on transgenerational inheritance in C. elegans recombinant inbred advanced intercross lines (RIAILs) and yeast segregants. We divided the RIAILs and segregants into two groups of high and low minor allele content (MAC). RIAILs with higher MAC needed less generations of benzaldehyde training to gain a stable olfactory imprint and showed a greater change from normal after benzaldehyde training. Yeast segregants with higher MAC showed a more dramatic shortening of the lag phase length after ethanol exposure. The short lag phase as acquired by ethanol training was more dramatically lost after recovery in ethanol free medium for the high MAC group. We also found a preferential association between MAC and traits linked with higher number of additive QTLs. These results suggest a role for the collective effects of SNPs in transgenerational inheritance, and may help explain human variations in disease susceptibility. Copyright © 2015. Published by Elsevier Inc.
    Genomics 04/2015; 106(1). DOI:10.1016/j.ygeno.2015.04.002 · 2.28 Impact Factor
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    • "In natural populations, male frequencies and outcrossing rates are low (Barrière and Félix 2005, 2007). Genetic diversity in this species is also low, and there are large blocks of strong linkage disequilibrium, even extending across separate chromosomes (Rockman and Kruglyak 2009; Andersen et al. 2012). Patterns of genetic variation in natural populations provide evidence for recent and rapid selective sweeps (Andersen et al. 2012). "
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    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; 4(9). DOI:10.1534/g3.114.012914 · 3.20 Impact Factor
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