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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Protein stability imposes limits on organism complexity and speed of molecular evolution
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Protein stability imposes limits on organism complexity and speed of molecular evolution

机译：蛋白质的稳定性限制了生物的复杂性和分子进化的速度

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Classical population genetics a priori assigns fitness to alleles without considering molecular or functional properties of proteins that these alleles encode. Here we study population dynamics in a model where fitness can be inferred from physical properties of proteins under a physiological assumption that loss of stability of any protein encoded by an essential gene confers a lethal pheno-type. Accumulation of mutations in organisms containing Γ genes can then be represented as diffusion within the Γ-dimensional hypercube with adsorbing boundaries determined, in each dimension, by loss of a protein's stability and, at higher stability, by lack of protein sequences. Solving the diffusion equation whose parameters are derived from the data on point mutations in proteins, we determine a universal distribution of protein stabilities, in agreement with existing data. The theory provides a fundamental relation between mutation rate, maximal genome size, and ther-modynamic response of proteins to point mutations. It establishes a universal speed limit on rate of molecular evolution by predicting that populations go extinct (via lethal mutagenesis) when mutation rate exceeds approximately six mutations per essential part of genome per replication for mesophilic organisms and one to two mutations per genome per replication for thermophilic ones. Several RNA viruses function close to the evolutionary speed limit, whereas error correction mechanisms used by DNA viruses and nonmutant strains of bacteria featuring various genome lengths and mutation rates have brought these organisms universally ≈1,000-fold below the natural speed limit.
机译：经典的人口遗传先验地将适合性分配给等位基因，而不考虑这些等位基因编码的蛋白质的分子或功能特性。在这里，我们研究了一个模型中的种群动态，在该模型中，可以根据生理假设（由必需基因编码的任何蛋白质的稳定性丧失赋予致命的表型）的生理假设来推断适合度。然后，可以将包含Γ基因的生物中突变的积累表示为Γ维超立方体内的扩散，其吸附边界在每个维中均由蛋白质稳定性的丧失以及在更高的稳定性下由缺乏蛋白质序列决定。通过求解扩散方程，该方程的参数来自蛋白质中点突变的数据，我们确定了蛋白质稳定性的普遍分布，与现有数据一致。该理论提供了突变率，最大基因组大小和蛋白质对点突变的热力学响应之间的基本关系。它通过预测嗜温生物每次复制的每个基因组每个基本部分的突变率超过大约六个突变，而嗜热嗜热的每个基因组每个复制每个基因组一个至两个突变，从而预测种群灭绝（通过致命诱变），从而对分子进化速率建立普遍的速度限制。那些。几种RNA病毒的功能接近进化速度极限，而DNA病毒和具有各种基因组长度和突变率的细菌的非突变菌株所使用的纠错机制使这些生物普遍比自然速度极限低约1,000倍。

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