title: Evolution of enzymatic activities of testis-specific short-chain dehydrogenase/reductase in Drosophila.
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.
authors.affiliation: Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Zhang
authors.forename: Huyuan
authors.initials: H
authors.lastname: Yang
authors.forename: Manyuan
authors.initials: M
authors.lastname: Long
authors.forename: Liming
authors.initials: L
authors.lastname: Li
authors.forename: Antony M
authors.initials: AM
authors.lastname: Dean
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D055162:Biocatalysis / Q000187:drug effects; D020134:Catalytic Domain; D003198:Computer Simulation; D003902:Detergents / Q000494:pharmacology; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics*; D004795:Enzyme Stability / Q000187:drug effects; D019143:Evolution, Molecular; D064429:Fatty Acid Synthases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D050506:Mutant Chimeric Proteins / Q000737:chemistry / Q000235:genetics*; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D013379:Substrate Specificity / Q000187:drug effects; D013737:Testis / Q000201:enzymology*
chemical_list: D003902:Detergents; D029721:Drosophila Proteins; C400504:Jingwei protein, Drosophila; D050506:Mutant Chimeric Proteins; D000426:Alcohol Dehydrogenase; C036543:short chain trans-2-enoyl-CoA reductase; D009247:NADH, NADPH Oxidoreductases; D064429:Fatty Acid Synthases
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