School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.
Science. 2013 Jun 14;340(6138):1324-7. doi: 10.1126/science.1236862.
Epistatic interactions between mutant sites in the same protein can exert a strong influence on pathways of molecular evolution. We performed protein engineering experiments that revealed pervasive epistasis among segregating amino acid variants that contribute to adaptive functional variation in deer mouse hemoglobin (Hb). Amino acid mutations increased or decreased Hb-O2 affinity depending on the allelic state of other sites. Structural analysis revealed that epistasis for Hb-O2 affinity and allosteric regulatory control is attributable to indirect interactions between structurally remote sites. The prevalence of sign epistasis for fitness-related biochemical phenotypes has important implications for the evolutionary dynamics of protein polymorphism in natural populations.
在同一种蛋白质中的突变位点之间的上位性相互作用可以对分子进化途径产生强烈影响。我们进行了蛋白质工程实验,揭示了在导致鹿鼠血红蛋白(Hb)适应性功能变异的分离氨基酸变异体之间普遍存在的上位性。氨基酸突变增加或降低了 Hb-O2 亲和力,这取决于其他位点的等位基因状态。结构分析表明,Hb-O2 亲和力和变构调节控制的上位性归因于结构上遥远的位点之间的间接相互作用。与适合度相关的生化表型的符号上位性的普遍性对自然种群中蛋白质多态性的进化动态具有重要意义。