We know little about several important properties of beneficial mutations, including their mutational origin, their phenotypic effects (e.g., protein structure changes vs. regulatory changes), and the frequency and rapidity with which they become fixed in a population. One signature of the spread of beneficial mutations is the reduction of heterozygosity at linked sites. Here, we present population genetic data from several loci across chromosome arm 2R in Drosophila simulans. A 100-kb segment from a freely recombining region of this chromosome shows extremely reduced heterozygosity in a California population sample, yet typical levels of divergence between species, suggesting that at least one episode of strong directional selection has occurred in the region. The 5 flanking sequence of one gene in this region, Cyp6g1 (a cytochrome P450), is nearly fixed for a Doc transposable element insertion. Presence of the insertion is correlated with increased transcript abundance of Cyp6g1, a phenotype previously shown to be associated with insecticide resistance in Drosophila melanogaster. Surveys of nucleotide variation in the same genomic region in an African D. simulans population revealed no evidence for a high-frequency Doc element and no evidence for reduced polymorphism. These data are consistent with the notion that the Doc element is a geographically restricted beneficial mutation. Data from D. simulans Cyp6g1 are paralleled in many respects by data from its sister species D. melanogaster.T he spread of beneficial mutations is expected to reduce variation at linked sites, a phenomenon known as genetic hitchhiking (1, 2). All else being equal, the size of the swept region depends on the selection coefficient of the beneficial mutant and the local recombination rate. Theoretical results show that for regions of normal recombination in Drosophila, hitchhiking effects associated with moderately strong selection should result in localized regions of reduced heterozygosity (3). Thus, in principle, the frequency and locations of selective sweeps can be determined by scanning chromosomes for ''valleys'' of reduced variation (4). The paucity of large genomic regions of severely reduced heterozygosity from recombining regions in Drosophila and other organisms (4-7) suggests that novel mutations with large positive selection coefficients are rare, although it does not rule out the evolutionary importance of such mutations.In this study, we document the existence of a 100-kb chromosomal region that has extremely reduced heterozygosity in a Drosophila simulans population sample from California, but not in a sample from Africa, indicating the recent and geographically restricted sweep of a unique, beneficial mutation. Furthermore, we report the unusual observation of an intact transposable element in this region, which occurs at very high frequency in the California, but not Africa, sample. The transposon insertion is associated with increased transcript abundance of the downstream cytochrome P450 gene Cyp6g1. These data are...