Department of Systems Biology, Columbia University, New York, NY 10032, USA.
BiomEdit, Fishers, IN 46037, USA.
Mol Biol Evol. 2024 Oct 4;41(10). doi: 10.1093/molbev/msae200.
Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues, specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.
理解蛋白质进化的主要决定因素是生物学中的一个基本挑战。尽管已经进行了几十年的积极研究，但细胞蛋白进化率具有很大可变性的分子和细胞机制目前还没有得到很好的理解。此外，蛋白质的分子功能在多细胞物种的背景下是如何被优化的，以及为什么许多蛋白质（如酶）平均来说只有中等的效率，这些问题仍然不清楚。我们对基因组学和功能数据集的分析在多个生物体中揭示了蛋白质分子功能的最优性与蛋白质进化率之间存在很强的负相关关系。此外，我们发现高表达的蛋白质往往具有更高的功能优化。这些结果表明，细胞表达成本导致丰富的蛋白质具有更明显的功能优化，而维持高功能优化水平的净化选择则显著减缓了蛋白质进化的速度。我们观察到，在多细胞物种中，蛋白质进化的速度和蛋白质功能效率的程度主要受到几种不同细胞类型和组织中表达的影响，特别是在动物中具有上调的突触过程的发育神经元，以及在植物中年轻和快速生长的组织中。总的来说，我们的分析揭示了来自分子、细胞和物种水平的组织的各种约束因素如何共同影响蛋白质进化的速度和蛋白质功能适应的水平。
