Natural and Synthetic Alleles Provide Complementary Insights into the Nature of Selection Acting on the Men Polymorphism of Drosophila Melanogaster

Abstract

Two malic enzyme alleles, Men113A and Men113G, occur at approximately equal frequency in North American populations of Drosophila melanogaster, while only Men113A occurs in African populations. We investigated the population genetics, biochemical characteristics, and selective potential of these alleles. Comparable levels of nucleotide polymorphism in both alleles suggest that the Men113G allele is not recently derived, but we find no evidence in the DNA sequence data for selection maintaining the polymorphism. Interestingly, the alleles differ in both Vmax and Km for the substrate malate. Triglyceride concentration and isocitrate dehydrogenase (IDH) and glucose-6-phosphate dehydrogenase (G6PD) activities are negatively correlated with the in vivo activities of the Men alleles. We examined the causality of the observed correlations using P-element excision-derived knockout alleles of the Men gene and found significant changes in the maximum activities of both IDH and G6PD, but not in triglyceride concentration, suggesting compensatory interactions between MEN, IDH, and G6PD. Additionally, we found significantly higher than expected levels of MEN activity in knockout heterozygotes, which we attribute to transvection effects. The distinct differences in biochemistry and physiology between the naturally occurring alleles and between the engineered alleles suggest the potential for selection on the Men locus.

Department(s)

Biological Sciences

Keywords and Phrases

glucose 6 phosphate dehydrogenase; isocitrate dehydrogenase; malate dehydrogenase (decarboxylating); triacylglycerol; Africa; allele; controlled study; DNA polymorphism; DNA sequence; Drosophila melanogaster; enzyme activity; gene interaction; genetic polymorphism; genetic selection; insect genetics; knockout gene; nonhuman; nucleotide sequence; population genetics; priority journal; protein DNA interaction; protein interaction; protein variant; triacylglycerol blood level; Alleles; Animals; Base Sequence; DNA Primers; Gene Deletion; Genetics; Population; Glucosephosphate Dehydrogenase; Malate Dehydrogenase; Malates; Molecular Sequence Data; Polymorphism; Genetic; Selection (Genetics); Sequence Analysis; DNA; Insecta

International Standard Serial Number (ISSN)

0016-6731

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2005 Genetics Society of America, All rights reserved.

Publication Date

01 Dec 2005

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