Evolution of Enzymatic Activities of Testis-Specific Short-Chain Dehydrogenase/Reductase in Drosophila

The testis-specific gene Jingwei (jgw) is a newly evolved short-chain dehydrogenase/reductase in Drosophila. Preliminary substrate screening indicated that JGW prefers long-chain primary alcohols as substrates, including several exotic alcohols such as farnesol and geraniol. Using steady-state kinetics analyses and molecular docking, we not only confirmed JGW's substrate specificity, but also demonstrated that the new enzymatic activities of JGW evolved extensively after exon-shuffling from a preexisting enzyme. Analysis of JGW orthologs in sister species shows that subsequent evolutionary changes following the birth of JGW altered substrate specificities and enzyme stabilities. Our results lend support to a general mechanism for the evolution of a new enzyme, in which catalytic chemistry evolves first followed by diversification of substrate utilization.