Abstract
Antagonistic host-parasite interactions can drive rapid adaptive evolution in genes of the immune system, and such arms races may be an important force shaping polymorphism in the genome. The RNA interference pathway gene Argonaute-2 (AGO2) is a key component of antiviral defense in Drosophila, and we have previously shown that genes in this pathway experience unusually high rates of adaptive substitution. Here we study patterns of genetic variation in a 100-kbp region around AGO2 in three different species of Drosophila. Our data suggest that recent independent selective sweeps in AGO2 have reduced genetic variation across a region of more than 50 kbp in Drosophila melanogaster, D. simulans, and D. yakuba, and we estimate that selection has fixed adaptive substitutions in this gene every 30-100 thousand years. The strongest signal of recent selection is evident in D. simulans, where we estimate that the most recent selective sweep involved an allele with a selective advantage of the order of 0.5-1% and occurred roughly 13-60 Kya. To evaluate the potential consequences of the recent substitutions on the structure and function of AGO2, we used fold-recognition and homology-based modeling to derive a structural model for the Drosophila protein, and this suggests that recent substitutions in D. simulans are overrepresented at the protein surface. In summary, our results show that selection by parasites can consistently target the same genes in multiple species, resulting in areas of the genome that have markedly reduced genetic diversity.
