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Biological Effects of Single-Nucleotide Polymorphisms in the Drosophila melanogaster Malic Enzyme Locus

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Abstract

A pair of amino acid polymorphisms within the Drosophila melanogaster Malic enzyme (Men) locus presents an interesting case of genetic variation that appears to be under selection. The two alleles at each site are biochemically distinct, but their biological effects are unknown. One polymorphic site is near the active site and the other is buried within the protein. Strikingly, in twelve different populations, the first polymorphism is always found at approximately a 50:50 allelic frequency, whereas the second polymorphism is always found at approximately 90:10. The consistency of the frequencies between populations suggests that the polymorphisms are under selection and it is possible that balancing selection is at play. We used 16 lines of flies to create the nine genotypes needed to quantify both effects of the polymorphic sites and possible genetic background effects, which we found to be widespread. The alleles at each site differ, but in different biochemical characteristics. The first site significantly influences MEN Km and Vmax, whereas the second site affects the Km and the Vmax/Km ratio (relative activity). Interestingly, the rarest allele is the most biochemically distinct. We also assayed three more distal phenotypes, triglyceride concentration, carbohydrate concentration, and longevity. In all cases, the phenotypes of the heterozygous genotypes are intermediate between those of the respective homozygotes suggesting that if balancing selection is maintaining the observed allele frequencies it is not through non-linear combinations of the biochemical phenotypes.

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Acknowledgements

This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-2018–05551) and Canada Research Chair (950–230113) to TJSM. The authors thank Drs Nadia Singh, Guangdong Yang, and Eric Gauthier for reading earlier versions of this manuscript.

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  1. Department of Chemistry & Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada

    Simran Baath & Thomas J. S. Merritt

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  1. Simran Baath
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  2. Thomas J. S. Merritt
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Correspondence to Thomas J. S. Merritt.

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Baath, S., Merritt, T.J.S. Biological Effects of Single-Nucleotide Polymorphisms in the Drosophila melanogaster Malic Enzyme Locus. Biochem Genet 58, 129–156 (2020). https://doi.org/10.1007/s10528-019-09932-2

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