Molecular population genetics of ref(2)P, a locus which confers viral resistance in Drosophila

The ref(2)P locus (2-54.2) is polymorphic for two allelic forms in naturalpopulations of Drosophila melanogaster, ref(2)Po and ref(2)Pp. The latterallele confers resistance to the rhabdovirus sigma infecting wildpopulations. Previous work, based on a small sample of prescreenedrestrictive (resistant) and permissive (susceptible) alleles, identified alarge number of amino acid replacement changes (7) relative to synonymouschanges (1). Such protein variability could be the result ofvariation-enhancing selection. To further test the selection hypothesis, wehave examined the DNA sequences of ten randomly chosen lines of D.melanogaster and one line of D. simulans. Nine of the ten lines arepermissive; D. simulans does not harbor the virus. The melanogaster allelescontain 4 synonymous changes, 19 noncoding changes, and 13 amino acidreplacement changes, indicating a relatively high level of polymorphism.Three sequenced restrictive alleles have nearly identical sequences,indicating that they are relatively young. Compared to the permissivealleles, they share only a complex deletion at codon 34, CAG-AAT to GGA,which our analysis indicates to be the site conferring the restrictivephenotype. Patterns of polymorphism and divergence differ from neutralpredictions by several criteria for the amino terminal region, whichcontains the complex deletion (codons 1-91), but not the remainder of theprotein (codons 92-599). We find a higher rate of evolution on the D.melanogaster lineage than on the D. simulans lineage. The relatively largeamount of both replacement and silent polymorphism in the permissivealleles and the lack of divergence between permissive and restrictivealleles suggests that the sigma virus and ref(2)P may be engaged in anevolutionary race in which new restrictive alleles are continually arisingbut are relatively short-lived.