The extensive and condition-dependent nature of epistasis among whole-genome duplicates in yeast
The extensive and condition-dependent nature of epistasis among whole-genome duplicates in yeast
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DOI：
10.1101/gr.076174.108
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发表时间：
2008-07-01
期刊：
影响因子：
7
通讯作者：
Zhang, Zhaolei
中科院分区：
文献类型：
--
作者：
Musso, Gabriel;Costanzo, Michael;Zhang, Zhaolei
由于现存的重复（旁系同源）之间的完全冗余在进化上是不利的，因此最终会失去一定程度的功能一致性。然而，在芽殖酵母中，针对重复代谢酶和全球物理相互作用调查收集的实验证据表明旁系同源物之间存在广泛的功能重叠。虽然保持功能重叠被认为赋予对遗传突变的鲁棒性并促进环境适应性，但尚未确定什么性质定义可以补偿删除姐妹基因的表型后果的旁系同源物，这种上位性有多广泛，以及它对替代环境状态的适应性如何。为此，我们已经进行了全面的实验分析上位性加剧旁系同源物之间的遗传相互作用，从一个古老的全基因组复制（WGD）事件发生在芽殖酵母酿酒酵母，从而能够比较大量的上位性和非上位性旁系同源物的属性相同的进化时间，因为分歧。我们发现，在标准实验室条件下，399个可检查的WGD parastasis对中超过三分之一（140）是上位性的，并且只有在设计用于诱导细胞应激的培养基条件下，上位性的额外情况才变得明显。尽管种内序列共保守显着增加，蛋白质相互作用的分析表明，旁系同源上位在标准实验室条件下没有更多的功能重叠比那些非上位。由于实验条件对被认为上位的旁系同源物的功能分类产生了影响，并且这里只询问了一小部分潜在的应激条件，我们假设许多上位关系仍未得到解决。
Since complete redundancy between extant duplicates (paralogs) is evolutionarily unfavorable, some degree of functional congruency is eventually lost. However, in budding yeast, experimental evidence collected for duplicated metabolic enzymes and in global physical interaction surveys had suggested widespread functional overlap between paralogs. While maintained functional overlap is thought to confer robustness against genetic mutation and facilitate environmental adaptability, it has yet to be determined what properties define paralogs that can compensate for the phenotypic consequence of deleting a sister gene, how extensive this epistasis is, and how adaptable it is toward alternate environmental states. To this end, we have performed a comprehensive experimental analysis of epistasis as indicated by aggravating genetic interactions between paralogs resulting from an ancient whole-genome duplication (WGD) event occurring in the budding yeast Saccharomyces cerevisiae, and thus were able to compare properties of large numbers of epistatic and non-epistatic paralogs with identical evolutionary times since divergence. We found that more than one-third ( 140) of the 399 examinable WGD paralog pairs were epistatic under standard laboratory conditions and that additional cases of epistasis became obvious only under media conditions designed to induce cellular stress. Despite a significant increase in within-species sequence co-conservation, analysis of protein interactions revealed that paralogs epistatic under standard laboratory conditions were not more functionally overlapping than those non-epistatic. As experimental conditions had an impact on the functional categorization of paralogs deemed epistatic and only a fraction of potential stress conditions have been interrogated here, we hypothesize that many epistatic relationships remain unresolved.