Abstract
In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution.
Highlights
The extent to which adaptive evolution has shaped the recent evolutionary history of humans is much debated
For GC content, we find a bimodal distribution, with peaks at both very fine scales (2 to 8 kb) and very broad scales (8 to 32 Mb)
Does biased gene conversion (BGC) Drive Base Composition Evolution? While the evidence presented suggests the action of BGC, and we find evidence of very local increases in GC content around recombination hotspots, we do not believe that BGC is sufficient to drive the evolution of base composition
Summary
The extent to which adaptive evolution has shaped the recent evolutionary history of humans is much debated. While polymorphism at certain genes, such as beta-globin or Duffy, is known to be associated with functional variation of selective importance, the functional importance of most DNA variation or substitution since the human-chimpanzee split is unknown. Adaptive evolution is expected to leave its footprint in patterns of genetic variation. Selective sweeps that accompany the fixation of adaptive mutations will eliminate nearby genetic variation [1]. In regions of high recombination, the footprint is expected to be smaller because recombination moves the beneficial mutation onto different genetic backgrounds, allowing linked diversity to persist. The observed positive correlation between recombination rate and genetic diversity [2,3,4] suggests that many loci have been the target of recent adaptive evolution
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