Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.
Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins across the Tree of Life.
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DOI：
10.1093/molbev/msw164
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发表时间：
2016-11
影响因子：
10.7
通讯作者：
Lane N
中科院分区：
文献类型：
--
作者：
Sojo V;Dessimoz C;Pomiankowski A;Lane N
膜蛋白在运输、信号传递、生物能量学、催化和药物靶标等方面起着至关重要的作用。在这里，我们表明，膜蛋白的可检测到的同源蛋白比水溶蛋白少得多，在大多数被分析的物种中不到一半。这种稀疏的分布可能反映了快速分化或基因丢失。我们发现，这两种机制都是有效的。首先，膜蛋白比水溶性蛋白进化得更快，特别是在它们面向外部的部分。其次，我们证明了预测的祖先膜蛋白在古菌和细菌的密切相关物种中优先丢失，而不是水溶蛋白。这些模式在整个生命树上是一致的，在古生物、细菌和真核生物这三个领域中的每一个领域都是一致的。我们的发现指出了一个基本的进化原理：膜蛋白由于在不断变化的环境中更强的适应性选择而进化得更快，而胞质蛋白在细胞内处于更严格的自我平衡的净化选择之下。这种作用在原核生物中应该是最强的，在单细胞真核生物中(有细胞内膜)较弱，在多细胞真核生物中最弱(有细胞外稳态)。我们证明确实是这样的。类似地，我们发现胞外水溶蛋白比膜蛋白表现出更强的低同源性模式。膜蛋白与水溶蛋白在保守性方面的这些显著差异对进化和医学具有重要意义。
Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis, and as drug targets. Here, we show that membrane proteins have dramatically fewer detectable orthologs than water-soluble proteins, less than half in most species analyzed. This sparse distribution could reflect rapid divergence or gene loss. We find that both mechanisms operate. First, membrane proteins evolve faster than water-soluble proteins, particularly in their exterior-facing portions. Second, we demonstrate that predicted ancestral membrane proteins are preferentially lost compared with water-soluble proteins in closely related species of archaea and bacteria. These patterns are consistent across the whole tree of life, and in each of the three domains of archaea, bacteria, and eukaryotes. Our findings point to a fundamental evolutionary principle: membrane proteins evolve faster due to stronger adaptive selection in changing environments, whereas cytosolic proteins are under more stringent purifying selection in the homeostatic interior of the cell. This effect should be strongest in prokaryotes, weaker in unicellular eukaryotes (with intracellular membranes), and weakest in multicellular eukaryotes (with extracellular homeostasis). We demonstrate that this is indeed the case. Similarly, we show that extracellular water-soluble proteins exhibit an even stronger pattern of low homology than membrane proteins. These striking differences in conservation of membrane proteins versus water-soluble proteins have important implications for evolution and medicine.
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影响因子：
4.4
作者：
Hedin, Linnea E.;Illergard, Kristoffer;Elofsson, Arne
通讯作者：
Elofsson, Arne
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
30.8
作者：
Pál, C;Papp, B;Lercher, MJ
通讯作者：
Lercher, MJ
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
DOI：
10.1016/j.nhtm.2014.08.001
发表时间：
2014-09-01
期刊：
NEW HORIZONS IN TRANSLATIONAL MEDICINE
影响因子：
--
作者：
Denayer, Tinneke;Stoehr, Thomas;Van Roy, Maarten
通讯作者：
Van Roy, Maarten