A Combination of Structural and Cis-Regulatory Factors Drives Biochemical Differences in Drosophila melanogaster Malic Enzyme

Abstract

The evolutionary significance of molecular variation is still contentious, with much current interest focusing on the relative contribution of structural changes in proteins versus regulatory variation in gene expression. We present a population genetic and biochemical study of molecular variation at the malic enzyme locus (Men) in Drosophila melanogaster. Two amino acid polymorphisms appear to affect substrate-binding kinetics, while only one appears to affect thermal stability. Interestingly, we find that enzyme activity differences previously assigned to one of the polymorphisms may, instead, be a function of linked regulatory differences. These results suggest that both regulatory and structural changes contribute to differences in protein function. Our examination of the Men coding sequences reveals no evidence for selection acting on the polymorphisms, but earlier work on this enzyme indicates that the biochemical variation observed has physiological repercussions and therefore could potentially be under natural selection.

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Acknowledgments

This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (3414-07) and Canada Research Chair (950-215763) to TJSM. TZR was supported by a NSERC Undergraduate Student Research Award and a Laurentian University Research Fund award.

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Correspondence to Thomas J. S. Merritt.

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Rzezniczak, T.Z., Lum, T.E., Harniman, R. et al. A Combination of Structural and Cis-Regulatory Factors Drives Biochemical Differences in Drosophila melanogaster Malic Enzyme. Biochem Genet 50, 823–837 (2012). https://doi.org/10.1007/s10528-012-9523-3

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Keywords

  • Malic enzyme (Men)
  • Molecular evolution
  • Genetic variation
  • Enzyme function