Molecular evolution of the Est-6 gene in Drosophila melanogaster: contrasting patterns of DNA variability in adjacent functional regions

We have investigated nucleotide polymorphism at the esterase 6 gene (Est-6) gene, including the complete coding region (1686 bp), as well as the 5'-flanking (1183 bp) and 3'-flanking (193 bp) regions of the gene, in 30 strains of Drosophila melanogaster and in one strain of Drosophila simulans. The level of silent variation is similar in the coding and in the 3'-flanking region, but smaller in the 5'-flanking region. Strong linkage disequilibrium occurs within each region; and also, although less pronounced, between the 5'-flanking region and the rest of the gene, including the 3'-flanking region. We suggest that the pattern of nucleotide polymorphism of Est-6 may be shaped by: (1) directional and balancing selection acting on the promoter and the coding region; and (2) interactions between the two regions that involve variable degrees of hitchhiking. The patterns of linkage disequilibrium, as well as the statistics Z(nS) (Genetics 146 (1997)1197) and B and Q (Genet. Res. 74 (1999) 65), may be interpreted as there being multiple targets of selection within the gene. The previously reported Est-6 allozyme latitudinal clines may be accounted for by the interaction between selective processes in the promoter and coding regions.