Segregation Distorter Causes Sweep Figure 4. Polytene chromosome squashes reveal two overlapping inversions on arm 2R of ten SD chromosomes. The In(2R)Mal arrangement is endemic in African populations and involves two inversions, In(2R)51B6–11;55E3–12 and In(2R)44F3–12;54E3–10. doi:10.1371/journal.pgen.1000463.g004 controls, we crossed heterozygous SD-MD31/cn bw females to cn bw males (SD-MD31 is inversion free). Among progeny from the SD-MD31 control crosses with a standard arrangement second chromosome, 34.8% carried recombinant chromosomes (n = 2,155 progeny). In contrast, the In(2R)Mal arrangement almost entirely eliminates crossing over between cn and bw: among progeny from crosses with the In(2R)Mal-bearing SD-NK04 chromosome, only 0.2% carried recombinant chromosomes (n = 1,564). By restricting recombination with wildtype chromosomes, In(2R)Mal sequesters a large piece of chromosome arm 2R as an effectively non- recombining region. The lack of recombination helps to explain the long-range LD produced by the selective sweep (Figure 3) as well as the strong population differentiation at loci between SD- Mal and inversion free chromosomes (Snn = 1.0, P#0.0001 [51], for the Sd-RanGAP to 55B regions concatenated; Table 4). We next assayed the strength of segregation distortion by estimating k, the proportion of progeny inheriting SD chromo- somes from heterozygous SD/Rsps males. In preliminary work, we found that the dominantly marked balancer chromosome, In(2LR)Gla (hereafter, Gla), carries a sensitive Responder (Rsps). We therefore measured transmission from heterozygous SD/Gla flies (see Methods). Surprisingly, the two SD chromosomes bearing the minor haplotype showed no detectable distortion: k* = 0.53860.025 for SD-BN19 and k* = 0.41560.012 for SD-MD31 (mean k*6s.e. are corrected for viability; Table 5). SD-BN19 and SD-MD31 chromosomes also failed to cause distortion when heterozygous against the super-sensitive Rspss allele of the lt pk cn bw chromosome (not shown). In contrast, males heterozygous for SD-Mal chromosomes collectively sired 10,664 progeny and failed to produce a single Rsps-bearing offspring (k* = 1.0; Table 5). The genetic and phenotypic data on recombination and distortion thus provide a clear explanation for the rise of the major haplotype- bearing SD-Mal chromosomes in Africa: they recombine less and distort more. The Age of the SD Sweep The complete absence of even low frequency polymorphisms in ,8.1 kb of sequence distributed from Sd-RanGAP on 2L to cytological subdivision 55B on 2R (G) suggests that SD-Mal rose to high frequency among SD chromosomes quickly and recently. To obtain estimates of the upper 95% confidence limit for the age of the sweep, we assumed that the genealogy relating SD-Mal Table 4. Genetic differentiation between SD and non-SD chromosomes. Population comparison SD (12) vs. wildtype (10) SD-Mal (10) vs. wildtype (10) Snn Fst Snn Fst M 37B 0.655 0.119 0.620 0.081 J 43E 0.841** 0.406 1.000** 0.581 P,0.001 and ** P,0.0001, where probabilities determined by 10,000 permutations of the data. doi:10.1371/journal.pgen.1000463.t004 K 45C 0.864* 0.423 0.950** 0.529 7 E 48D6 0.848** 0.599 1.000** 0.771 F 51E 0.777** 0.088 0.855** 0.230 G 55B 0.541* 0.032 0.514 0.032 H 58E 0.314 20.024 0.379 20.012 I 59E 0.462 20.019 0.373 20.043 PLoS Genetics | www.plosgenetics.org May 2009 | Volume 5 | Issue 5 | e1000463