Epistatic interactions modulate the evolution of mammalian mitochondrial respiratory complex components.
Epistatic interactions modulate the evolution of mammalian mitochondrial respiratory complex components.
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DOI：
10.1186/1471-2164-10-266
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发表时间：
2009-06-13
期刊：
影响因子：
4.4
通讯作者：
Amorim A
中科院分区：
文献类型：
--
作者：
Azevedo L;Carneiro J;van Asch B;Moleirinho A;Pereira F;Amorim A
突变的有害影响可以通过第二个相互作用的残基逆转。这是一个上位性的补偿过程，解释了为什么在某些物种中有害的突变在系统发育相关的谱系中是被容忍的，这表明这些突变无论如何都只在特定物种的背景下是有害的。尽管关于补偿进化的广泛和完善的理论框架确实存在，但支持证据仍然有限，特别是对于蛋白质模型。在这项研究中，我们结合了深入的结构和序列分析，重点研究了哺乳动物线粒体OXPHOS蛋白上位性代偿过程的分子机制。在这项研究中，模拟的人类结构被用来分别预测结构损伤和有害突变的恢复，并与相互作用的补偿伙伴结合。在两种情况下，COI和COIII，空间连接残基之间的分子内相互作用恢复了被有害突变破坏的折叠模式。在第三种情况下，线粒体CyB和细胞核CyT1编码的细胞色素Bc1复合体成分之间的分子间接触可能恢复蛋白质结合。此外，我们观察到了不同的补偿进化模式，这些模式要么导致突变和相应的补偿伙伴几乎同时发生，要么导致不同谱系中总是在补偿位置之前的突变的独立发生。涉及有害突变的个体替换之间的上位性相互作用似乎遵循一种简约的进化模式，在这种模式下，基因组保持预补偿状态，随后容忍有害突变。这一现象很可能限制了共同进化位点的可变性，并塑造了线粒体和核基因组之间的相互作用。
The deleterious effect of a mutation can be reverted by a second-site interacting residue. This is an epistatic compensatory process explaining why mutations that are deleterious in some species are tolerated in phylogenetically related lineages, rendering evident that those mutations are, by all means, only deleterious in the species-specific context. Although an extensive and refined theoretical framework on compensatory evolution does exist, the supporting evidence remains limited, especially for protein models. In this current study, we focused on the molecular mechanism underlying the epistatic compensatory process in mammalian mitochondrial OXPHOS proteins using a combination of in-depth structural and sequence analyses. Modeled human structures were used in this study to predict the structural impairment and recovery of deleterious mutations alone and combined with an interacting compensatory partner, respectively. In two cases, COI and COIII, intramolecular interactions between spatially linked residues restore the folding pattern impaired by the deleterious mutation. In a third case, intermolecular contact between mitochondrial CYB and nuclear CYT1 encoded components of the cytochrome bc1 complex are likely to restore protein binding. Moreover, we observed different modes of compensatory evolution that have resulted in either a quasi-simultaneous occurrence of a mutation and corresponding compensatory partner, or in independent occurrences of mutations in distinct lineages that were always preceded by the compensatory site. Epistatic interactions between individual replacements involving deleterious mutations seems to follow a parsimonious model of evolution in which genomes hold pre-compensating states that subsequently tolerate deleterious mutations. This phenomenon is likely to have been constraining the variability at coevolving sites and shaping the interaction between the mitochondrial and the nuclear genome.
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影响因子：
30.8
作者：
Kern, AD;Kondrashov, FA
通讯作者：
Kondrashov, FA
影响因子：
1.5
作者：
Higgs, PG
通讯作者：
Higgs, PG
影响因子：
56.9
作者：
Kulathinal, RJ;Bettencourt, BR;Hartl, DL
通讯作者：
Hartl, DL
影响因子：
2.8
作者：
MANFREDI, G;SCHON, EA;DIMAURO, S
通讯作者：
DIMAURO, S
DOI：
10.1073/pnas.1932834100
发表时间：
2003-09-30
影响因子：
11.1
作者：
Chen, Y;Stephan, W
通讯作者：
Stephan, W