AMINO-ACID POLYMORPHISM AND RARE ELECTROPHORETIC VARIANTS OF G6PD FROM NATURAL-POPULATIONS OF DROSOPHILA-MELANOGASTER

Identifying the amino acid changes responsible for electrophoretic var iants is essential to understanding the significance of allozyme polym orphism in adaptation. The amino acid mutations responsible for the co mmon G6PD allozyme polymorphisms in Drosophila melanogaster have been recently described. This study characterizes the amino acid changes as sociated with 11 rare electrophoretic G6PD variants. The 11 rare elect rophoretic variants result from six independent amino acid mutations. The in vivo function of the rare variants was determined in an earlier study and most variants fell into one of two function classes. It is shown here that the function of the rare variants reflects the state o f the Pro/Leu mutation responsible for the A/B allozyme polymorphism i n each variant. Two mutations destabilize quaternary structure resulti ng in shifts from tetrameric to dimeric alleles, and one of these also results in a variant with in vivo function intermediate to A and B. T hat mutation is an aspartic-acid-to-asparagine change that is two resi dues away from the Pro/Leu polymorphism responsible for the A/B dimert etramer quaternary shift. Structure-function relationships based on st udies of human G6PD deficency-associated mutations predict that these last two amino acid changes fall within the protein domain responsible for NADP binding.