An episode of accelerated amino acid change in Drosophila esterase-6 associated with a change in physiological function

In most lineages of the subgenus Sophophora esterase-6 is a homodimeric hae molymph protein. In the melanogaster subgroup of species it has become a mo nomer which is mainly expressed in the male sperm ejaculatory duct. Our ana lyses of esterase-6 sequences from three melanogaster subgroup species and two close relatives reveal a brief period of accelerated amino acid sequenc e change during the transition between the ancestral and derived states. In this period of 2-6Myr the ratio of replacement to silent site substitution s (0.51) is about three times higher than the values in other lineages of t he phylogeny. There are about 50 more replacements in this period than woul d be predicted from the ratios of replacement to silent site substitutions found elsewhere in the phylogeny. Modelling on the known structure of a rel ated acetylcholinesterase suggests that an unusually high proportion of the replacements in the transitional branch are non-conservative changes on th e protein surface. Up to half the accelerated replacement rate can be accou nted for by clusters of changes to the face of the molecule containing the opening of the active site gorge. This includes changes in and around regio ns homologous to peripheral substrate binding sites in acetylcholinesterase . There are also three changes in glycosylation status. One region predicte d to lie on the protein surface which becomes markedly more hydrophilic is proposed to be the ancestral dimerisation site that is lost in the transiti onal branch.