Department of Systems Biology, Center for Computational Biology and Bioinformatics, Columbia University, New York City, NY 10032, USA, Integrated Program in Cellular, Molecular, Structural, and Genetic Studies, Columbia University, New York City, NY 10032, USA and Department of Biomedical Informatics, Columbia University, New York City, NY 10032, USA.
Nucleic Acids Res. 2014 Feb;42(4):2405-14. doi: 10.1093/nar/gkt1200. Epub 2013 Nov 27.
Gene duplications are a major source of evolutionary innovations. Understanding the functional divergence of duplicates and their role in genetic robustness is an important challenge in biology. Previously, analyses of genetic robustness were primarily focused on duplicates essentiality and epistasis in several laboratory conditions. In this study, we use several quantitative data sets to understand compensatory interactions between Saccharomyces cerevisiae duplicates that are likely to be relevant in natural biological populations. We find that, owing to their high functional load, close duplicates are unlikely to provide substantial backup in the context of large natural populations. Interestingly, as duplicates diverge from each other, their overall functional load is reduced. At intermediate divergence distances the quantitative decrease in fitness due to removal of one duplicate becomes smaller. At these distances, yeast duplicates display more balanced functional loads and their transcriptional control becomes significantly more complex. As yeast duplicates diverge beyond 70% sequence identity, their ability to compensate for each other becomes similar to that of random pairs of singletons.
基因重复是进化创新的主要来源。理解重复的功能分化及其在遗传稳健性中的作用是生物学中的一个重要挑战。以前，遗传稳健性的分析主要集中在几个实验室条件下重复的必需性和上位性。在这项研究中，我们使用了几个定量数据集来理解酿酒酵母重复之间可能在自然生物群体中相关的补偿相互作用。我们发现，由于它们的高功能负荷，紧密重复在大的自然种群中不太可能提供实质性的备份。有趣的是，随着重复彼此分化，它们的整体功能负荷减少。在中等分化距离下，由于去除一个重复而导致的适应性降低变得更小。在这些距离上，酵母重复显示出更平衡的功能负荷，其转录控制变得明显更加复杂。当酵母重复的序列同一性超过 70%时，它们彼此补偿的能力变得类似于随机单倍体对的能力。
