Article

Journal of Molecular Evolution

, Volume 71, Issue 4, pp 241-249

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

  • Jianming ZhangAffiliated withDepartment of Ecology and Evolution, The University of ChicagoDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • , Huyuan YangAffiliated withDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • , Manyuan LongAffiliated withDepartment of Ecology and Evolution, The University of Chicago
  • , Liming LiAffiliated withDepartment of Molecular Pharmacology and Biological Chemistry, The Feinberg School of Medicine, Northwestern University Email author 
  • , Antony M. DeanAffiliated withThe BioTechnology Institute, University of Minnesota, 240 Gortner Laboratories Email author 

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Abstract

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.

Keywords

Enzyme evolution Short-chain dehydrogenase/reductase Drosophila alcohol dehydrogenase Exon-shuffling Drosophila