Data from: The biochemical architecture of an ancient adaptive landscape

Molecular evolution is moving from statistical descriptions of adaptive molecular changes toward predicting the fitness effects of mutations. Here, we characterize the fitness landscape of the six amino acids controlling coenzyme use in isopropylmalate dehydrogenase (IMDH). Although all natural IMDHs use nicotinamide adenine dinucleotide (NAD) as a coenzyme, they can be engineered to use nicotinamide adenine dinucleotide phosphate (NADP) instead. Intermediates between these two phenotypic extremes show that each amino acid contributes additively to enzyme function, with epistatic contributions confined to fitness. The genotype-phenotype-fitness map shows that NAD use is a global optimum.

分子进化正从针对适应性分子变化的统计学描述，转向预测突变的适合度效应。本研究对控制异丙基苹果酸脱氢酶（isopropylmalate dehydrogenase, IMDH）辅酶使用的6种氨基酸的适合度景观（fitness landscape）进行了系统表征。尽管所有天然IMDH均以烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide, NAD）为辅酶，但可通过工程改造使其改用烟酰胺腺嘌呤二核苷酸磷酸（nicotinamide adenine dinucleotide phosphate, NADP）。这两种表型极端之间的中间表型显示，每种氨基酸对酶功能均呈加性贡献，而上位效应的影响仅局限于适合度层面。基因型-表型-适合度图谱（genotype-phenotype-fitness map）显示，使用NAD为全局最优表型。