Positive selection has driven the evolution of the Drosophila insulin-like receptor (InR) at different timescales

The highly conserved insulin-signaling pathway influences very diverse processes including intermediary metabolism, reproduction, aging, and growth. The first pathway component is the insulin receptor that upon insulin binding triggers the signal-transduction cascade. Its variation, like that of other pathway components, might therefore affect many organismal traits. Variation at the "Insulin-like" receptor (InR) gene was surveyed both within Drosophila melanogaster and between species across the Drosophila phylogeny. In D. melanogaster, the level and pattern of variation at the approximately 8-kb region surveyed did not provide any indication of a recent selective event in this region. Maximum likelihood (ML) analyses revealed the past action of purifying selection acting differentially both across the phylogeny and along the studied gene. Moreover, the ML analyses and the McDonald and Kreitman test revealed the footprint of positive selection driving amino acid changes to fixation in the branch separating the Sophophora and the Drosophila subgenera, and in the D. melanogaster lineage, respectively. The oldest selective events could have affected either the insulin binding or the signal-transduction capacities of the receptor, whereas mutations affecting signal transduction would seem to underlie the more recent events.