Adaptive Threonine Increase in Transmembrane Regions of Mitochondrial Proteins in Higher Primates
Adaptive Threonine Increase in Transmembrane Regions of Mitochondrial Proteins in Higher Primates
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DOI：
10.1371/journal.pone.0003343
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发表时间：
2008-10-06
期刊：
影响因子：
3.7
通讯作者：
Tanaka, Masashi
中科院分区：
文献类型：
--
作者：
Kitazoe, Yasuhiro;Kishino, Hirohisa;Tanaka, Masashi
背景：与核基因树相比，胎盘哺乳动物的线粒体 (mt) 基因树揭示了氨基酸 (AA) 替代率的强烈加速以及导致高等灵长类动物 (猿猴) 的谱系中 AA 组成偏差的变化。这种加速和组成偏差是否是由 AA 水平的适应性进化或 DNA 水平的定向突变压力引起的，一直存在激烈争论。方法/主要发现：我们的系统发育分析表明，猿类谱系的速率加速伴随着 mt DNA 编码蛋白跨膜螺旋区域中苏氨酸 (Thr) 残基的显着增加。 Thr 的增加涉及膜内部疏水性 AA 的替换。即使考虑到由于系统发育而缺乏独立性，回归分析也显示灵长类动物的 Thr 组成与寿命之间存在统计上显着的正相关性。 结论/意义：由于 Thr 和 Ser 在膜蛋白中的关键作用被认为是形成氢键增强螺旋-螺旋相互作用，因此在高等灵长类动物中检测到的 Thr 增加可能是通过增强内膜中 mt 蛋白的稳定性来适应的。膜内部的苏氨酸组成与动物寿命之间的相关性是惊人的，特别是因为一些线粒体功能被认为与衰老有关。
Background: The mitochondrial (mt) gene tree of placental mammals reveals a very strong acceleration of the amino acid (AA) replacement rate and a change in AA compositional bias in the lineage leading to the higher primates (simians), in contrast to the nuclear gene tree. Whether this acceleration and compositional bias were caused by adaptive evolution at the AA level or directional mutation pressure at the DNA level has been vigorously debated.Methodology/Principal Findings: Our phylogenetic analysis indicates that the rate acceleration in the simian lineage is accompanied by a marked increase in threonine (Thr) residues in the transmembrane helix regions of mt DNA-encoded proteins. This Thr increase involved the replacement of hydrophobic AAs in the membrane interior. Even after accounting for lack of independence due to phylogeny, a regression analysis reveals a statistical significant positive correlation between Thr composition and longevity in primates.Conclusion/Significance: Because crucial roles of Thr and Ser in membrane proteins have been proposed to be the formation of hydrogen bonds enhancing helix-helix interactions, the Thr increase detected in the higher primates might be adaptive by serving to reinforce stability of mt proteins in the inner membrane. The correlation between Thr composition in the membrane interior and the longevity of animals is striking, especially because some mt functions are thought to be involved in aging.