4.8 Article

Fine-scale mapping of recombination rate in Drosophila refines its correlation to diversity and divergence

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0801848105

Keywords

variation; crossing over

Funding

  1. NIGMS NIH HHS [GM076051, R01 GM076051] Funding Source: Medline

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Regional rates of recombination often correlate with levels of nucleotide diversity, and either selective or neutral hypotheses can explain this relationship. Regional recombination rates also correlate with nucleotide differences between human and chimpanzee, consistent with models where recombination is mutagenic; however, a lack of correlation is observed in the Drosophila melanogaster group, consistent with models invoking natural selection. Here, we revisit the relationship among recombination, diversity, and interspecies difference by generating empirical estimates of these parameters in Drosophila pseudoobscura. To measure recombination rate, we genotyped 1,294 backcross hybrids at 50 markers across the largest assembled linkage group in this species. Genome-wide diversity was estimated by sequencing a second isolate of D. pseudoobscura at shallow coverage. Alignment to the sequenced genome of the closely related species, Drosophila persimilis, provided nucleotide site orthology. Our findings demonstrate that scale is critical in determining correlates to recombination rate: fine-scale cross-over rate estimates are far stronger predictors of both diversity and interspecies difference than broad-scale estimates. The correlation of fine-scale recombination rate to diversity and interspecies difference appears to be genome-wide, evidenced by examination of an X-linked region in greater detail. Because we observe a strong correlation of cross-over rate with interspecies difference, even after correcting for segregating ancestral variation, we suggest that both mutagenic and selective forces generate these correlations, the latter in regions of low crossing over. We propose that it is not cross-overs per se that are mutagenic, but rather repair of DNA double-strand break precursors via crossing over and gene conversion.

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