Genome-Wide Fine-Scale Recombination Rate Variation in Drosophila melanogaster

Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and diversity. Author Summary: Recombination is a process by which chromosomes exchange genetic material during meiosis. It is important in evolution because it provides offspring with new combinations of genes, and so estimating the rate of recombination is of fundamental importance in various population genomic inference problems. In this paper, we develop a new statistical method to enable robust estimation of fine-scale recombination maps of Drosophila, a genus of common fruit flies, in which the background recombination rate is high and natural selection has been prevalent. We apply our method to produce fine-scale recombination maps for a North American population and an African population of D. melanogaster. For both populations, we find extensive fine-scale variation in recombination rate throughout the genome. We provide a quantitative characterization of the similarities and differences between the recombination maps of the two populations; our study reveals high correlation at broad scales and low correlation at fine scales, as has been documented among human populations. We also examine the correlation between various genomic features. Furthermore, using a conservative approach, we find a handful of putative recombination “hotspot” regions with solid statistical support for a local elevation of at least 10 times the background recombination rate.