The Fine-Scale Structure of Recombination Rate Variation in the Human Genome

Abstract We examine the effect of variation in gene density per centimorgan on quantitative trait locus (QTL) mapping studies using data from the Drosophila melanogaster genome project and documented regional rates of recombination. There is tremendous variation in gene density per centimorgan across this genome, and we observe that this variation can cause systematic biases in QTL mapping studies. Specifically, in our simulated mapping experiments of 50 equal-effect QTL distributed randomly across the physical genome, very strong QTL are consistently detected near the centromeres of the two major autosomes, and few or no QTL are often detected on the X chromosome. This pattern persisted with varying heritability, marker density, QTL effect sizes, and transgressive segregation. Our results are consistent with empirical data collected from QTL mapping studies of this species and its close relatives, and they explain the “small X-effect” that has been documented in genetic studies of sexual isolation in the D. melanogaster group. Because of the biases resulting from recombination rate variation, results of QTL mapping studies should be taken as hypotheses to be tested by additional genetic methods, particularly in species for which detailed genetic and physical genome maps are not available.

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The genomic landscape of recombination rate variation in Chlamydomonas reinhardtii reveals a pronounced effect of linked selection

10.1101/340992 ◽

2018 ◽

Cited By ~ 1

Author(s):

Ahmed R. Hasan ◽

Rob W. Ness

Keyword(s):

Chlamydomonas Reinhardtii ◽

Recombination Rate ◽

Natural Populations ◽

Gc Content ◽

Sexual Cycle ◽

Rate Variation ◽

Effective Population ◽

Entire Genome ◽

Recombination Rate Variation ◽

Linked Selection

AbstractRecombination confers a major evolutionary advantage by breaking up linkage disequilibrium (LD) between harmful and beneficial mutations and facilitating selection. Here, we use genome-wide patterns of LD to infer fine-scale recombination rate variation in the genome of the model green alga Chlamydomonas reinhardtii and estimate rates of LD decay across the entire genome. We observe recombination rate variation of up to two orders of magnitude, finding evidence of recombination hotspots playing a role in the genome. Recombination rate is highest just upstream of genic regions, suggesting the preferential targeting of recombination breakpoints in promoter regions. Furthermore, we observe a positive correlation between GC content and recombination rate, suggesting a role for GC-biased gene conversion or selection on base composition within the GC-rich genome of C. reinhardtii. We also find a positive relationship between nucleotide diversity and recombination, consistent with widespread influence of linked selection in the genome. Finally, we use estimates of the effective rate of recombination to calculate the rate of sex that occurs in natural populations of this important model microbe, estimating a sexual cycle roughly every 770 generations. We argue that the relatively infrequent rate of sex and large effective population size creates an population genetic environment that increases the influence of linked selection on the genome.

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