NUCLEOTIDE SEQUENCE VARIATION OF ALCOHOL DEHYDROGENASE IN DROSOPHILA MELANOGASTER

A comparative DNA sequence analysis of eleven cloned Drosophila melanogaster alcohol dehydrogenase genes from five natural populations has revealed thirty-eight nucleotide and three length polymorphisms within the structural locus. Only one of fourteen polymorphisms in the coding regions produces an amino acid replacement, thr-lys at codon 192, which defines the electrophoretic polymorphism, Adh-f - Adh-s. This disparity implies that most amino acid replacements in Adh have been selectively deleterious. However, the magnitude of selection against such mutations need not be large.

Only two of the eleven genes were found to be identical to one another. The five Adh-f alleles differed, on average, from the six Adh-s alleles by 23 substitutions (including insertion/deletion) over a 2.7 kilobase region including the complete structural locus and a 800 base pair 3' flanking region. Although there was also considerable variability within the two classes of alleles, identical or closely related sequences were broadly distributed geographically, suggesting there is little long-term geographical isolation in the species.

The distribution of shared nucleotides among the polymorphic positions in the eleven alleles contains evidence for intragenic recombination in the structural gene. Two intragenic recombinations are inferred from the sequence analysis.

An 800bp 3' flanking region is highly conserved among the eleven alleles, exhibiting a one order of magnitude lower level of polymorphism than silent polymorphisms in the exons and introns. The region contains no long open reading frames suggestive of a structural locus. Either this large region is highly constrained by yet undetermined functions or it has a low rate of mutation.