{"title":"Most Pleiotropic Effects of Gene Knockouts Are Evolutionarily Transient in Yeasts.","authors":"Li Liu, Yao Liu, Lulu Min, Zhenzhen Zhou, Xingxing He, YunHan Xie, Waifang Cao, Shuyun Deng, Xiaoju Lin, Xionglei He, Xiaoshu Chen","doi":"10.1093/molbev/msae189","DOIUrl":null,"url":null,"abstract":"<p><p>Pleiotropy, the phenomenon in which a single gene influences multiple traits, is a fundamental concept in genetics. However, the evolutionary mechanisms underlying pleiotropy require further investigation. In this study, we conducted parallel gene knockouts targeting 100 transcription factors in 2 strains of Saccharomyces cerevisiae. We systematically examined and quantified the pleiotropic effects of these knockouts on gene expression levels for each transcription factor. Our results showed that the knockout of a single gene generally affected the expression levels of multiple genes in both strains, indicating various degrees of pleiotropic effects. Strikingly, the pleiotropic effects of the knockouts change rapidly between strains in different genetic backgrounds, and ∼85% of them were nonconserved. Further analysis revealed that the conserved effects tended to be functionally associated with the deleted transcription factors, while the nonconserved effects appeared to be more ad hoc responses. In addition, we measured 184 yeast cell morphological traits in these knockouts and found consistent patterns. In order to investigate the evolutionary processes underlying pleiotropy, we examined the pleiotropic effects of standing genetic variations in a population consisting of ∼1,000 hybrid progenies of the 2 strains. We observed that newly evolved expression quantitative trait loci impacted the expression of a greater number of genes than did old expression quantitative trait loci, suggesting that natural selection is gradually eliminating maladaptive or slightly deleterious pleiotropic responses. Overall, our results show that, although being prevalent for new mutations, the majority of pleiotropic effects observed are evolutionarily transient, which explains how evolution proceeds despite complicated pleiotropic effects.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":null,"pages":null},"PeriodicalIF":11.0000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414406/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular biology and evolution","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/molbev/msae189","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pleiotropy, the phenomenon in which a single gene influences multiple traits, is a fundamental concept in genetics. However, the evolutionary mechanisms underlying pleiotropy require further investigation. In this study, we conducted parallel gene knockouts targeting 100 transcription factors in 2 strains of Saccharomyces cerevisiae. We systematically examined and quantified the pleiotropic effects of these knockouts on gene expression levels for each transcription factor. Our results showed that the knockout of a single gene generally affected the expression levels of multiple genes in both strains, indicating various degrees of pleiotropic effects. Strikingly, the pleiotropic effects of the knockouts change rapidly between strains in different genetic backgrounds, and ∼85% of them were nonconserved. Further analysis revealed that the conserved effects tended to be functionally associated with the deleted transcription factors, while the nonconserved effects appeared to be more ad hoc responses. In addition, we measured 184 yeast cell morphological traits in these knockouts and found consistent patterns. In order to investigate the evolutionary processes underlying pleiotropy, we examined the pleiotropic effects of standing genetic variations in a population consisting of ∼1,000 hybrid progenies of the 2 strains. We observed that newly evolved expression quantitative trait loci impacted the expression of a greater number of genes than did old expression quantitative trait loci, suggesting that natural selection is gradually eliminating maladaptive or slightly deleterious pleiotropic responses. Overall, our results show that, although being prevalent for new mutations, the majority of pleiotropic effects observed are evolutionarily transient, which explains how evolution proceeds despite complicated pleiotropic effects.
期刊介绍:
Molecular Biology and Evolution
Journal Overview:
Publishes research at the interface of molecular (including genomics) and evolutionary biology
Considers manuscripts containing patterns, processes, and predictions at all levels of organization: population, taxonomic, functional, and phenotypic
Interested in fundamental discoveries, new and improved methods, resources, technologies, and theories advancing evolutionary research
Publishes balanced reviews of recent developments in genome evolution and forward-looking perspectives suggesting future directions in molecular evolution applications.