Eanes W F, Kirchner M, Taub D R, Yoon J, Chen J T
Department of Ecology and Evolution, State University of New York, Stony Brook 11794, USA.
Genetics. 1996 May;143(1):401-6. doi: 10.1093/genetics/143.1.401.
Identifying the amino acid changes responsible for electrophoretic variants is essential to understanding the significance of allozyme polymorphism in adaptation. The amino acid mutations responsible for the common G6PD allozyme polymorphisms in Drosophila melanogaster have been recently described. This study characterizes the amino acid changes associated with 11 rare electrophoretic G6PD variants. The 11 rare electrophoretic 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 of the Pro/Leu mutation responsible for the A/B allozyme polymorphism in each variant. Two mutations destabilize quaternary structure resulting in shifts from tetrameric dimeric alleles, and one of these also results in a variant with in vivo function intermediate to A and B. That mutation is an aspartic-acid-to-asparagine change that is two residues away from the Pro/Leu polymorphism responsible for the A/B dimertetramer quaternary shift. Structure-function relationships based on studies of human G6PD deficiency-associated mutations predict that these last two amino acid changes fall within the protein domain responsible for NADP binding.
确定导致电泳变异体的氨基酸变化对于理解等位酶多态性在适应性方面的意义至关重要。最近已经描述了果蝇中常见的G6PD等位酶多态性所涉及的氨基酸突变。本研究对与11种罕见的电泳G6PD变异体相关的氨基酸变化进行了表征。这11种罕见的电泳变异体源于六个独立的氨基酸突变。在早期的一项研究中确定了这些罕见变异体的体内功能，大多数变异体属于两种功能类别之一。本文表明，罕见变异体的功能反映了每种变异体中导致A/B等位酶多态性的Pro/Leu突变状态。两个突变使四级结构不稳定，导致从四聚体向二聚体等位基因转变，其中一个突变还产生了一种体内功能介于A和B之间的变异体。该突变是天冬氨酸到天冬酰胺的变化，距离导致A/B二聚体/四聚体四级结构转变的Pro/Leu多态性有两个残基。基于对人类G6PD缺乏相关突变的研究得出的结构-功能关系预测，这最后两个氨基酸变化位于负责NADP结合的蛋白质结构域内。
