Evolutionary Rate Covariation in Meiotic Proteins Results from Fluctuating Evolutionary Pressure in Yeasts and Mammals

Evolutionary Rate Covariation in Meiotic Proteins Results from Fluctuating Evolutionary Pressure in Yeasts and Mammals
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DOI:
10.1534/genetics.112.145979
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发表时间:
2013-02-01
期刊:
影响因子:
3.3
通讯作者:
Aquadro, Charles F.
Aquadro, Charles F.
中科院分区:
生物学2区
文献类型:
--
作者:
Clark, Nathan L.;Alani, Eric;Aquadro, Charles F.

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功能相关蛋白质的进化速率往往随着进化时间的推移而平行变化。这种进化速率共变(ERC)是一种基于序列的共同进化特征,也是推断蛋白质之间功能关系的潜在有用特征。解释 ERC 的一个主要假设是,作用于整个通路的进化压力的波动会导致功能相关蛋白质的平行速率变化。为了探索这一假设,我们分析了 18 个酵母物种和 22 个哺乳动物物种的系统发育中 DNA 错配修复 (MMR) 和减数分裂蛋白中的 ERC。我们在参与减数分裂交换的八种酵母蛋白之间发现了 ERC 的强特征,这似乎是由于光滑念珠菌中的限制放松所致。光滑 C. glabrata 中的这些和其他减数分裂蛋白显示出显着的速率加速,可能是由于其明显的克隆繁殖策略以及由此导致的减数分裂蛋白的不频繁使用。生殖模式的变化和约束变化之间的这种相关性支持了 ERC 的进化压力起源。此外,我们还提供了在其他致病酵母物种中类似放松限制的证据。哺乳动物 MMR 和减数分裂蛋白也显示出具有统计学意义的 ERC;然而,正如在酵母中观察到的那样,交叉蛋白之间没有很强的 ERC。相反,哺乳动物通过不同的途径表现出 ERC,例如 piRNA 介导的针对转座元件的防御。总的来说,如果进化压力的波动是 ERC 的原因,那么它就可以揭示整个蛋白质通路内的功能关系,无论它们是否物理上相互作用,只要该通路的约束存在变化。
Evolutionary rates of functionally related proteins tend to change in parallel over evolutionary time. Such evolutionary rate covariation (ERC) is a sequence-based signature of coevolution and a potentially useful signature to infer functional relationships between proteins. One major hypothesis to explain ERC is that fluctuations in evolutionary pressure acting on entire pathways cause parallel rate changes for functionally related proteins. To explore this hypothesis we analyzed ERC within DNA mismatch repair (MMR) and meiosis proteins over phylogenies of 18 yeast species and 22 mammalian species. We identified a strong signature of ERC between eight yeast proteins involved in meiotic crossing over, which seems to have resulted from relaxation of constraint specifically in Candida glabrata. These and other meiotic proteins in C. glabrata showed marked rate acceleration, likely due to its apparently clonal reproductive strategy and the resulting infrequent use of meiotic proteins. This correlation between change of reproductive mode and change in constraint supports an evolutionary pressure origin for ERC. Moreover, we present evidence for similar relaxations of constraint in additional pathogenic yeast species. Mammalian MMR and meiosis proteins also showed statistically significant ERC; however, there was not strong ERC between crossover proteins, as observed in yeasts. Rather, mammals exhibited ERC in different pathways, such as piRNA-mediated defense against transposable elements. Overall, if fluctuation in evolutionary pressure is responsible for ERC, it could reveal functional relationships within entire protein pathways, regardless of whether they physically interact or not, so long as there was variation in constraint on that pathway.