Callahan Benjamin J
Department of Applied Physics, Stanford University, Stanford, CA, USA.
Fly (Austin). 2012 Jan-Mar;6(1):16-20. doi: 10.4161/fly.18305. Epub 2012 Jan 1.
Central to the study of molecular evolution, and an area of long-standing debate, is the appropriate model for the fitness landscape of proteins. Much of this debate has focused on the strength and frequency of positive and purifying selection, but the form and frequency of selective correlations is also a vital element. The constituent amino acids within a protein generically interact and share selective pressures in predictable ways, which conflicts with the selective independence assumed by common caricatures of the fitness landscape. Here, I discuss a recent study by myself and coauthors that used whole-genome comparisons of orthologous molecular sequences from closely related Drosophilids to explore the form of the selective correlations and selective interactions (epistasis) between the amino acids within a protein. I outline our results and highlight our finding of a selective length scale of ten amino acids within which individual amino acids are substantially and generically more likely to share selective pressures and interact epistatically. I then focus on the evidence presented in our study supporting a substantial role for epistasis in the process of molecular evolution, and discuss further the implications of this widespread epistasis on the overdispersion of the molecular clock and the efficacy of common tests for positive selection.
蛋白质适应性景观的合适模型是分子进化研究的核心，也是一个长期存在争议的领域。这场争论大多集中在正选择和纯化选择的强度及频率上，但选择相关性的形式和频率也是一个关键因素。蛋白质中的组成氨基酸通常以可预测的方式相互作用并共享选择压力，这与适应性景观常见简化描述中假设的选择独立性相矛盾。在此，我将讨论我与合著者最近进行的一项研究，该研究利用亲缘关系较近的果蝇直系同源分子序列的全基因组比较，来探究蛋白质中氨基酸之间选择相关性和选择相互作用（上位性）的形式。我将概述我们的研究结果，并着重介绍我们的发现：存在一个十个氨基酸的选择长度尺度，在这个尺度内，单个氨基酸更有可能普遍且显著地共享选择压力并发生上位性相互作用。然后，我将重点关注我们研究中提出的支持上位性在分子进化过程中发挥重要作用的证据，并进一步讨论这种广泛存在的上位性对分子钟过度离散以及正选择常用检验功效的影响。
