MOLECULAR POPULATION-GENETICS OF REF(2)P, A LOCUS WHICH CONFERS VIRALRESISTANCE IN DROSOPHILA

The ref(2)P locus (2-54.2) is polymorphic for two allelic forms in nat ural populations of Drosophila melanogaster, ref(2)P-o and ref(2)P-p. The latter allele confers resistance to the rhabdovirus sigma infectin g wild populations. Previous work, based on a small sample of prescree ned restrictive (resistant) and permissive (susceptible) alleles, iden tified a large number of amino acid replacement changes (7) relative t o synonymous changes (1). Such protein variability could be the result of variation-enhancing selection. To further test the selection hypot hesis, we have examined the DNA sequences of ten randomly chosen lines of D. melanogaster and one line of D. simulans. Nine of the ten lines are permissive; D. simulans does not harbor the virus. The melanogast er alleles contain 4 synon ymous changes, 19 noncoding changes, and 13 amino acid replacement changes, indicating a relatively high level of polymorphism. Three sequenced restrictive alleles have nearly identic al sequences, indicating that they are relatively young. Compared to t he permissive alleles, they share only a complex deletion at codon 34, CAG-AAT to GGA, which our analysis indicates to be the site conferrin g the restrictive phenotype. Patterns of polymorphism and divergence d iffer from neutral predictions by several criteria for the amino termi nal region, which contains the complex deletion (codons 1-91), but not the remainder of the protein (codons 92-599). We find a higher rate o f evolution on the D. melanogaster lineage than on the D. simulans lin eage. The relatively large amount of both replacement and silent polym orphism in the permissive alleles and the lack of divergence between p ermissive and restrictive alleles suggests that the sigma virus and re f(2)P may be engaged in an evolutionary race in which new restrictive alleles are continually arising but are relatively short-lived.