From DNA to fitness differences: sequences and structures of adaptive variants of Colias phosphoglucose isomerase (PGI).

From DNA to fitness differences: sequences and structures of adaptive variants of Colias phosphoglucose isomerase (PGI).
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从 DNA 到适应性差异:Colias 磷酸葡萄糖异构酶 (PGI) 适应性变体的序列和结构。

DOI:
10.1093/molbev/msj062
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发表时间:
2006
影响因子:
10.7
通讯作者:
Schulte,PatriciaM
Schulte,PatriciaM
中科院分区:
生物学1区
文献类型:
--
作者:
Wheat,ChristopherW;Watt,WardB;Pollock,DavidD;Schulte,PatriciaM

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广红蝶大肠杆菌在磷酸葡萄糖异构酶(PGI)中表现出广泛的等位酶多态性。早期对这些基因型的生物化学和适应性影响的研究发现了在野生环境中保持这种多态性的强大自然选择的证据。在这里,我们分析了这种多态性的分子特征,通过测序多个等位基因和建模它们的结构。PGI是具有旋转对称性的二聚体。每个单体为另一个单体的催化中心提供关键残基。测序的等位基因在多个氨基酸位置上不同,包括隐藏的电荷中性变异,但电晶型等位基因之间最一致的差异是在电荷变化的氨基酸位点。通过结构和功能分析及其变体的群体频率鉴定的主要候选选择位点发生在单体之间界面的互穿环中,在那里它们可能改变亚基相互作用和催化中心几何形状。与第二个(和基础)物种相比,在自然选择下PGI也具有多态性的米氏大肠杆菌揭示了它们的PGI之间的一个固定氨基酸差异,该差异位于互穿环中,并伴随着它们变体之间的功能差异。我们还研究了PGI等位基因之间的核苷酸变异性,将这些数据与另一种糖酵解酶基因甘油醛-3-磷酸脱氢酶的类似数据进行比较。尽管广泛的非同义和同义多态性在PGI在每个物种中,物种之间固定的唯一的碱基变化是两个引起氨基酸替换;这种同义固定的情况下产生一个显着的麦克唐纳-Kreitman测试。对这些数据的分析表明,历史上人口增长。田岛D统计的正峰值,代表中性的“搭便车”的区域,被发现周围的主要候选网站的选择。这项研究提供了新的观点的分子结构机制,并开始的历史证据,在PGI在这些和其他物种的长期持久的平衡酶多态性。
Colias eurythemebutterflies display extensive allozyme polymorphism in the enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness effects of these genotypes found evidence of strong natural selection maintaining this polymorphism in the wild. Here we analyze the molecular features of this polymorphism by sequencing multiple alleles and modeling their structures. PGI is a dimer with rotational symmetry. Each monomer provides a critical residue to the other monomer's catalytic center. Sequenced alleles differ at multiple amino acid positions, including cryptic charge-neutral variation, but most consistent differences among the electromorph alleles are at the charge-changing amino acid sites. Principal candidate sites of selection, identified by structural and functional analyses and by their variants' population frequencies, occur in interpenetrating loops across the interface between monomers, where they may alter subunit interactions and catalytic center geometry. Comparison to a second (and basal) species,Colias meadii, also polymorphic for PGI under natural selection, reveals one fixed amino acid difference between their PGIs, which is located in the interpenetrating loop and accompanies functional differences among their variants. We also study nucleotide variability among the PGI alleles, comparing these data to similar data from another glycolytic enzyme gene, glyceraldehyde-3-phosphate dehydrogenase. Despite extensive nonsynonymous and synonymous polymorphism at PGI in each species, the only base changes fixed between species are the two causing the amino acid replacement; this absence of synonymous fixation yields a significant McDonald-Kreitman test. Analyses of these data suggest historical population expansion. Positive peaks of Tajima'sDstatistic, representing regions of neutral “hitchhiking,” are found around the principal candidate sites of selection. This study provides novel views of molecular-structural mechanisms, and beginnings of historical evidence, for a long-persistent balanced enzyme polymorphism at PGI in these and perhaps other species.
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