THE HITCHHIKING EFFECT ON THE SITE FREQUENCY-SPECTRUM OF DNA POLYMORPHISMS

The level of DNA sequence variation is reduced in regions of the Droso phila melanogaster genome where the rate of crossing over per physical distance is also reduced. This observation has been interpreted as su pport for the simple model of genetic hitchhiking, in which directiona l selection on rare variants, e.g., newly arising advantageous mutants , sweeps linked neutral alleles to fixation, thus eliminating polymorp hisms near the selected site. However, the frequency spectra of segreg ating sites of several loci from some populations exhibiting reduced l evels of nucleotide diversity and reduced numbers of segregating sites did not appear different from what would be expected under a neutral equilibrium model. Specifically, a skew toward an excess of rare sites was not observed in these samples, as measured by Tajima's D. Because this skew was predicted by a simple hitchhiking model, yet it had nev er been expressed quantitatively and compared directly to DNA polymorp hism data, this paper investigates the hitchhiking effect on the site frequency spectrum, as measured by Tajima's D and several other statis tics, using a computer simulation model based on the coalescent proces s and recurrent hitchhiking events. The results presented here demonst rate that under the simple hitchhiking model (1) the expected value of Tajima's D is large and negative (indicating a skew toward rare varia nts), (2) that Tajima's test has reasonable power to detect a skew in the frequency spectrum for parameters comparable to those from actual data sets, and (3) that the Tajima's Ds observed in several data sets are very unlikely to have been the result of simple hitchhiking. Conse quently, the simple hitchhiking model is not a sufficient explanation for the DNA polymorphism at those loci exhibiting a decreased number o f segregating sites yet not exhibiting a skew in the frequency spectru m.