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

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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.

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Abbreviations

JGW:

Jingwei

SDR:

Short-chain dehydrogenase/reductase

ADH:

Alcohol dehydrogenase

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Acknowledgments

We thank all the members in the Dean laboratory at the University of Minnesota, Li laboratory at Northwestern University, and Long laboratory at the University of Chicago for experimental assistance and helpful discussions. This study was supported by grants to A.M.D. from the National Institutes of Health, L.L from National Institute of Health (R01NS056086), and M.L. from the National Science Foundation and the National Institutes of Health, a National Science Foundation CAREER award, and a Packard Fellowship in Science and Engineering. Hinds fund from the University of Chicago to J.Z.

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Correspondence to Liming Li or Antony M. Dean.

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239_2010_9384_MOESM1_ESM.doc

Supplementary material: Supplementary material includes data of structural based sequence alignment and Ramachandran Plot of JGW protein: D. teissieri and D. yakuba JGW. (DOC 329 kb)

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Zhang, J., Yang, H., Long, M. et al. Evolution of Enzymatic Activities of Testis-Specific Short-Chain Dehydrogenase/Reductase in Drosophila . J Mol Evol 71, 241–249 (2010). https://doi.org/10.1007/s00239-010-9384-5

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  • DOI: https://doi.org/10.1007/s00239-010-9384-5

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