Large-Scale Selective Sweep among Segregation Distorter Chromosomes in African Populations of Drosophila melanogaster Daven C. Presgraves1,2*, Pierre R. Ge´ rard1, Anjuli Cherukuri1, Terrence W. Lyttle3 1 Department of Biology, University of Rochester, Rochester, New York, United States of America, 2 Radcliffe Institute for Advanced Study, Harvard University, Cambridge, Massachusetts, United States of America, 3 Department of Cell and Molecular Biology, University of Hawaii, Honolulu, Hawaii, United States of America Abstract Segregation Distorter (SD) is a selfish, coadapted gene complex on chromosome 2 of Drosophila melanogaster that strongly distorts Mendelian transmission; heterozygous SD/SD+ males sire almost exclusively SD-bearing progeny. Fifty years of genetic, molecular, and theory work have made SD one of the best-characterized meiotic drive systems, but surprisingly the details of its evolutionary origins and population dynamics remain unclear. Earlier analyses suggested that the SD system arose recently in the Mediterranean basin and then spread to a low, stable equilibrium frequency (1–5%) in most natural populations worldwide. In this report, we show, first, that SD chromosomes occur in populations in sub-Saharan Africa, the ancestral range of D. melanogaster, at a similarly low frequency (,2%), providing evidence for the robustness of its equilibrium frequency but raising doubts about the Mediterranean-origins hypothesis. Second, our genetic analyses reveal two kinds of SD chromosomes in Africa: inversion-free SD chromosomes with little or no transmission advantage; and an African-endemic inversion-bearing SD chromosome, SD-Mal, with a perfect transmission advantage. Third, our population genetic analyses show that SD-Mal chromosomes swept across the African continent very recently, causing linkage disequilibrium and an absence of variability over 39% of the length of the second chromosome. Thus, despite a seemingly stable equilibrium frequency, SD chromosomes continue to evolve, to compete with one another, or evade suppressors in the genome. Citation: Presgraves DC, Ge´rard PR, Cherukuri A, Lyttle TW (2009) Large-Scale Selective Sweep among Segregation Distorter Chromosomes in African Populations of Drosophila melanogaster. PLoS Genet 5(5): e1000463. doi:10.1371/journal.pgen.1000463 Editor: Harmit S. Malik, Fred Hutchinson Cancer Research Center, United States of America Received February 3, 2009; Accepted March 30, 2009; Published May 1, 2009 Copyright: 2009 Presgraves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by funds to DCP from a NIH Ruth L. Kirschstein NRSA postdoctoral fellowship, the Radcliffe Institute for Advanced Study at Harvard University, and the University of Rochester. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: dvnp@mail.rochester.edu Introduction The Segregation Distorter (SD) system of the fruitfly, Drosophila melanogaster, is a naturally occurring meiotic drive complex— instead of fair Mendelian transmission, heterozygous SD/SD+ males transmit SD chromosomes to most, if not all, progeny [1–8]. Full strength distortion is caused by three interacting loci clustered around the centromere of chromosome 2 (an autosome): the trans- acting Segregation distorter (Sd) locus; an upward modifier, Enhancer of SD (E(SD)); and a cis-acting distortion-insensitive allele at the target locus, Responder (Rspi). (By convention, Sd refers to the locus whereas SD refers to chromosomes assumed to carry the full complex of loci.) SD chromosomes are thus Sd E(SD) Rspi, whereas SD+ chromosomes, which lack the distorting Sd locus and usually carry sensitive alleles of Rsp, are Sd+ E(SD)+ Rsps (Figure 1A). During spermiogenesis in heterozygous SD/SD+ males, the sperm-specific histone transition required for proper chromatin packaging is disrupted in Rsps-bearing SD+ sperm, leaving functional Rspi- bearing SD sperm to monopolize fertilization [9–12]. For decades, the SD system has been a model in evolutionary genetics, not only for being selfish, propagating at the expense of its bearers, but as a coadapted gene complex whose fitness is determined by multiple epistatic interactors [5–7,13–15]. The evolution and persistence of the SD complex depend critically on genetic linkage. Multilocus drive systems can only invade a population when recombination is restricted among loci, as the transmission advantage of distorter chromosomes (Sd Rspi) must not be offset by the formation of so-called ‘suicide’ chromosomes (Sd Rsps) that distort against themselves [16]. The clustering of SD loci around the centromere of chromosome 2, where crossing over is reduced, is therefore unsurprising [15]. Epistatic selection further favors the evolution of secondary suppressors of recombination [15,17,18]. Many SD chromosomes, for instance, have recruited a pericentric inversion, In(2LR)39D- 42A, that further reduces crossing over in the centromeric region, while some have recruited paracentric inversions on 2R (reviewed in [2,5,6,17]). The paracentric inversions are thought to reduce crossing over between the centromeric SD elements and modifiers of distortion distributed across 2R, such as Modifier of SD (M(SD)), Stabilizer of SD (St(SD)), and possibly others [19–22]. Thus, SD chromosomes have evolved a complex of multiple, epistatically interacting loci with coadapted alleles whose linkage relationships are usually further tightened by one or more chromosomal inversions. The geographic distribution of inversions on different SD chromosomes may shed light on the origins, and possibly the age, PLoS Genetics | www.plosgenetics.org 1 May 2009 | Volume 5 | Issue 5 | e1000463