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

Abstract

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 broadscale 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.variation ͉ crossing over O ne of the most influential observations in molecular evolutionary biology is the relationship between recombination rate and nucleotide diversity within species. In a pioneering study, Begun and Aquadro (1) identified a strong positive association between nucleotide polymorphism in Drosophila melanogaster (as measured from restriction site data of 20 loci) and recombination rate. If this relationship was caused by recombination itself being mutagenic, a similar relationship between recombination rate and nucleotide divergence to the sister species, Drosophila simulans, should also exist; however, this relationship was not observed. More recently, Begun et al.(2) examined whole-genome shotgun sequences from multiple strains of D. simulans and the published D. melanogaster genome assembly and confirmed these initial observations at an unprecedented scale. The association between recombination rate and diversity, but not divergence, in Drosophila is considered to be driven primarily by natural selection (3-5): fixation of positively selected variants and associated hitchhiking effects (6) and/or background selection eliminating deleterious alleles (7).Similar studies in o...

How closely does genetic diversity in finite populations conform to predictions of neutral theory? Large deficits in regions of low recombination

“…Nucleotide diversity across chromosomes is positively correlated with recombination rate in Drosophila (Begun and Aquadro, 1992;Shapiro et al, 2007;Kulathinal et al, 2008), humans (Hellmann et al, 2005), white-throated sparrows , tomatoes (Stephan and Langley, 1998) and maize (Tenaillon et al, 2001), but not in A. lyrata (Wright et al, 2006). In several Drosophila species, nucleotide diversity differs by B10-fold between regions of high and low recombination (Stephan et al, 1992;Aquadro et al, 1994;Begun et al, 2007).…”

Great majority of recombination events in Arabidopsis are gene conversion events

“…S6) suggests instead that either (i) there is a preference for DSBs to occur in domains of high polymorphism or (ii) DSBs promote polymorphism. The latter may be mediated by a coupling between DSB repair and the mutation process (32) or reflect the activity of biased gene conversion, which can increase load at gene conversion hot spots even if inbreeding levels are very high (33). Biased gene conversion is supported by SNP analysis (see above) and from the finding that in the 100-bp sequences around the tracts of gene conversion, the gene conversion content (0.368) in shared loci, with two or more gene conversions among different individuals, is higher than that at unshared (0.345) or randomly sampled loci (0.348; P = 14 × 10 −10 ).…”

Recombination rate variation in closely related species

“…First, conflicting results may simply reflect taxon-specific mutagenicity, but this hypothesis requires more empirical work. Second, correlations of diversity or divergence to recombination rate may change according to the scale with which recombination is assayed (Bussell et al, 2006;Spencer et al, 2006;Kulathinal et al, 2008;Noor, 2008a;Stevison and Noor, 2010), making it a priority to assess these measures using fine-scale recombination over varying magnitudes. Third, and most relevant to the primary topic of this review, many studies up to this point have only assayed recombination in one species of interest, assuming recombination rates are conserved.…”