Author Summary Mendel’s first law of segregation holds that a heterozygous parent will transmit alternative alleles to offspring equally. Segregation Distorter (SD) is a naturally occurring selfish gene complex in D. melanogaster that subverts Mendel’s first law. During spermatogenesis in heterozygous SD/SD+ males, SD effectively kills SD+-bearing sperm, monopoliz- ing fertilization. SD chromosomes carry a distorter gene and a complement of genetically linked enhancers, often held together by inversions. Thus, SD chromosomes are selfish, co-adapted gene complexes. Although SD is one of our best-characterized selfish gene systems, we still have a poor understanding of its evolutionary history and population dynamics. We therefore performed a large screen for SD chromosomes in African populations of D. melanogaster and studied their genetic properties and history. We found a new SD chromosome type, SD-Mal (endemic to Africa), that has a perfect transmission advantage and lacks recombination over much of the chromosome. This new SD chromosome rapidly swept across sub-Saharan Africa sometime within the last ,3,000 years. These findings show that selfish gene complexes evolve continuously to evade suppression by other genes in the genome and to compete with one another for a place in the population. Segregation Distorter Causes Sweep of the complex. SD can be found in nearly all populations of D. melanogaster at a frequency of ,1–5% [23] (but see ref. [24]). In North America, Hawaii, Japan, and Australia, SD chromosomes invariably carry inversions (though not necessarily the same ones). In Italy and Spain, however, both inversion-bearing and presumably ancestral, inversion-free SD chromosomes occur. The presence of both derived and ancestral types has been taken as evidence that SD chromosomes originated in the Mediterranean basin [3,4]. An origin in Mediterranean Europe further implies that the SD complex evolved recently, as D. melanogaster is a sub- Saharan African species whose range expanded to Europe only ,15,000 years ago, probably via a single major out-of-Africa founder event [25–28]. The first population genetic analysis of SD found little divergence between four loci on SD versus SD+ chromosomes, consistent with a recent origin for the complex [14,29]. Much about the evolutionary history and population dynamics of SD in natural populations remains unclear. For one, a recent, Mediterranean origin for SD in the D. melanogaster lineage has important implications, explaining its absence from closely related species and suggesting that the multiple genetic components of the complex evolved very quickly. But the Mediterranean origins hypothesis hinges on few data—the presence of inversion-free SD chromosomes from collections in Italy and Spain and nowhere else. For another, what little is known about the population Figure 1. A molecular screen for SD chromosomes. (A) Part of chromosome arm 2L and all of 2R are shown with the approximate cytological locations of SD loci. The centromere occurs at the transition between cytological divisions 40 and 41. (B) A three-primer assay was used to screen isofemale lines for the presence of the Sd-RanGAP duplication. There are two potential primer pairs: the F-R1 primer pair, a positive control, amplifies a 463-bp product from RanGAP; the F-R2 primer pair amplifies a 353-bp product from the proximal breakpoint of the Sd-RanGAP duplicate gene, if present. Note that the R2 primer anneals to the 59 region of both RanGAP and Sd-RanGAP; for Sd-RanGAP, however, there is no corresponding forward primer. An example gel is shown: flies carrying Sd-RanGAP yield two amplicons (from Sd-RanGAP and RanGAP), whereas those lacking Sd-RanGAP produce only one (from RanGAP only). doi:10.1371/journal.pgen.1000463.g001 PLoS Genetics | www.plosgenetics.org 2 May 2009 | Volume 5 | Issue 5 | e1000463