A combination of structural and cis-regulatory factors drives biochemical differences in Drosophila melanogaster malic enzyme.
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.
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON, P3E 2C6, Canada.
Teresa Z
TZ
Rzezniczak
Thomas E
TE
Lum
Robert
R
Harniman
Thomas J S
TJ
Merritt
D000595:Amino Acid Sequence; D000818:Animals; D059006:Chromosomes, Insect / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation; D004795:Enzyme Stability; D019143:Evolution, Molecular; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017344:Genes, Insect; D056426:Genetic Loci; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D019476:Insect Proteins / Q000737:chemistry* / Q000235:genetics; D008291:Malate Dehydrogenase / Q000737:chemistry* / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D012995:Solubility; D013379:Substrate Specificity
D019476:Insect Proteins; D008291:Malate Dehydrogenase; C034544:D-malate dehydrogenase (decarboxylating)