Darwin's theory of evolution emphasized that positive selection of functional proficiency provides the fitness that ultimately determines the structure of life, a view that has dominated biochemical thinking of enzymes as perfectly optimized for their specific functions. The 20th-century modern synthesis, structural biology, and the central dogma explained the machinery of evolution, and nearly neutral theory explained how selection competes with random fixation dynamics that produce molecular clocks essential e.g. for dating evolutionary histories. However, quantitative proteomics revealed that selection pressures not relating to optimal function play much larger roles than previously thought, acting perhaps most importantly via protein expression levels. This paper first summarizes recent progress in the 21st century toward recovering this universal selection pressure. Then, the paper argues that proteome cost minimization is the dominant, underlying ‘non-function’ selection pressure controlling most of the evolution of already functionally adapted living systems. A theory of proteome cost minimization is described and argued to have consequences for understanding evolutionary trade-offs, aging, cancer, and neurodegenerative protein-misfolding diseases.

中文翻译：

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最便宜的生存：蛋白质组成本最小化如何推动进化

达尔文的进化论强调，对功能熟练度的积极选择提供了最终决定生命结构的适应性，这一观点主导了酶的生化思维，因为它们的特定功能完美优化。20 世纪的现代综合、结构生物学和中心法则解释了进化的机制，而近乎中性的理论解释了选择如何与随机固定动力学竞争，从而产生分子钟，例如用于确定进化历史的日期。然而，定量蛋白质组学表明，与最佳功能无关的选择压力所起的作用比以前认为的要大得多，可能最重要的是通过蛋白质表达水平发挥作用。本文首先总结了 21 世纪在恢复这种普遍选择压力方面取得的最新进展。然后，该论文认为蛋白质组成本最小化是主导的、潜在的“非功能”选择压力，控制着已经适应功能的生命系统的大部分进化。蛋白质组成本最小化理论被描述并认为对理解进化权衡、衰老、癌症和神经退行性蛋白质错误折叠疾病有影响。