Center for Biosystems Dynamics Research (BDR), RIKEN, Osaka 565-0874, Japan.
Universal Biology Institute, School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
G3 (Bethesda). 2022 Nov 4;12(11). doi: 10.1093/g3journal/jkac235.
The evolutionary speed of a protein sequence is constrained by its expression level, with highly expressed proteins evolving relatively slowly. This negative correlation between expression levels and evolutionary rates (known as the E-R anticorrelation) has already been widely observed in past macroevolution between species from bacteria to animals. However, it remains unclear whether this seemingly general law also governs recent evolution, including past and de novo, within a species. However, the advent of genomic sequencing and high-throughput phenotyping, particularly for bacteria, has revealed fundamental gaps between the 2 evolutionary processes and has provided empirical data opposing the possible underlying mechanisms which are widely believed. These conflicts raise questions about the generalization of the E-R anticorrelation and the relevance of plausible mechanisms. To explore the ubiquitous impact of expression levels on molecular evolution and test the relevance of the possible underlying mechanisms, we analyzed the genome sequences of 99 strains of Escherichia coli for evolution within species in nature. We also analyzed genomic mutations accumulated under laboratory conditions as a model of de novo evolution within species. Here, we show that E-R anticorrelation is significant in both past and de novo evolution within species in E. coli. Our data also confirmed ongoing purifying selection on highly expressed genes. Ongoing selection included codon-level purifying selection, supporting the relevance of the underlying mechanisms. However, the impact of codon-level purifying selection on the constraints in evolution within species might be smaller than previously expected from evolution between species.
蛋白质序列的进化速度受到其表达水平的限制，表达水平高的蛋白质进化相对较慢。这种表达水平和进化速度之间的负相关关系（称为 E-R 反相关）已经在过去从细菌到动物的物种间的宏观进化中得到了广泛观察。然而，目前尚不清楚这一看似普遍的规律是否也支配着物种内的近期进化，包括过去和从头进化。然而，基因组测序和高通量表型分析的出现，特别是针对细菌的研究，揭示了这两个进化过程之间的根本差距，并提供了与广泛认为的可能潜在机制相悖的经验数据。这些冲突引发了关于 E-R 反相关的普遍性和可能潜在机制的相关性的问题。为了探索表达水平对分子进化的普遍影响并检验可能潜在机制的相关性，我们分析了 99 株大肠杆菌在自然界中种内进化的基因组序列。我们还分析了实验室条件下积累的基因组突变，作为种内从头进化的模型。在这里，我们表明 E-R 反相关在大肠杆菌的种内过去和从头进化中都是显著的。我们的数据还证实了高度表达基因的持续纯化选择。持续选择包括密码子水平的纯化选择，支持潜在机制的相关性。然而，与种间进化相比，密码子水平的纯化选择对种内进化的约束的影响可能较小。
