Purifying selection enduringly acts on the sequence evolution of highly expressed proteins in Escherichia coli

Abstract

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 ER 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 two 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 ER anticorrelation and the relevance of plausible mechanisms. To explore the ubiquitous impact of expression level on molecular evolution, and to test the relevance of the possible underlying mechanisms, we analyzed the genome sequences of 99 strains of Escherichia coli for microevolution in nature. We also analyzed genomic mutations accumulated under laboratory conditions as a model of de novo microevolution. Here, we show that the ER anticorrelation is significant in both past and de novo microevolution in E. coli. Our data also confirmed ongoing purifying selection acting on highly expressed genes. Ongoing selection included codon-level purifying selection, supporting the relevance of the underlying mechanisms. However, their contributions to the constraints in recent evolution might be smaller than previously expected from past macroevolution.

Gene expression is the main driver of purifying selection in large penguin populations

“…Considering diversity at the population level, E-R anticorrelation should explain differences in nonsynonymous and synonymous segregating polymorphisms (p) across genes (i.e., pN/pS or as the corrected estimate πN/πS). Although such a pattern has been observed in a few wild populations (Carneiro et al 2012, Williamson et al 2014, Hodgins et al 2016, Galtier et al 2016, recent laboratory experiments on model organisms have instead provided contrasting results (Wu et al 2022, Shibai et al 2022. More importantly, the relative contribution of gene expression and effective population size to purifying selection has not been empirically explored.…”

“…Evidence for E-R anticorrelation was found in interspecific comparisons by estimating nonsynonymous over synonymous (i.e., nearly neutral) fixation rates (dN/dS) in genes with different expression levels (Zhang and Yang 2015). However, only weak marks of anticorrelation between gene expression and genetic polymorphism (i.e., segregating nonsynonymous over synonymous variants, pN/pS) have recently been found in population-level genetic variation, but only in model organisms in controlled laboratory populations (Wu et al 2022, Shibai et al 2022. On the other hand, such effects have never been estimated in natural populations experiencing real-world selection regimes.…”