Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg, Austria.
Department of Systems Biology, Columbia University, New York, NY, United States of America.
PLoS Genet. 2019 Apr 10;15(4):e1008079. doi: 10.1371/journal.pgen.1008079. eCollection 2019 Apr.
Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Furthermore, at 67% of sites, amino acid replacements were under sign epistasis, having both strongly positive and negative effect in different genetic backgrounds. 46% of sites were under reciprocal sign epistasis. The fitness impact of amino acid replacements was influenced by only a few genetic backgrounds but involved interaction of multiple sites, shaping a rugged fitness landscape in which many of the shortest paths between highly fit genotypes are inaccessible.
描述适应度景观，即大量基因型的适应度表现，是理解遗传信息如何被解释以创造功能生物体的关键。在这里，我们确定了 His3 适应度景观的进化相关部分，His3 是编码组氨酸合成途径中酶的基因，重点关注在现存物种的同源位点发现的氨基酸状态组合。在酵母 His3 同源物中发现的只有 15%的氨基酸总是处于中性状态，而其余 85%的氨基酸对适应度的影响取决于遗传背景。此外，在 67%的位点上，氨基酸替换受到符号上位性的影响，在不同的遗传背景下具有强烈的正效应和负效应。46%的位点受到相互符号上位性的影响。氨基酸替换对适应度的影响只受到少数遗传背景的影响，但涉及多个位点的相互作用，形成了一个崎岖不平的适应度景观，其中许多高度适应的基因型之间的最短路径是无法到达的。
