Selection for Cheaper Amino Acids Drives Nucleotide Usage at the Start of Translation in Eukaryotic Genes

作     者：Na L.Gao Zilong He Qianhui Zhu Puzi Jiang Songnian Hu Wei-Hua Chen Na L.Gao;Zilong He;Qianhui Zhu;Puzi Jiang;Songnian Hu;Wei-Hua Chen

作者机构：Key Laboratory of Molecular Biophysics of the Ministry of EducationHubei Key Laboratory of Bioinformatics and Molecular-imagingDepartment of Bioinformatics and Systems BiologyCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Institute for Computer Science and Cluster of Excellence on Plant SciencesHeinrich Heine UniversityD-40225 DuesseldorfGermany CAS Key Laboratory of Genome Sciences and InformationBeijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China State Key Laboratory of Microbial ResourcesInstitute of MicrobiologyChinese Academy of SciencesBeijing 100101China Beijing Advanced Innovation Center for Big Data-Based Precision MedicineInterdisciplinary Innovation Institute of Medicine and EngineeringBeihang UniversityBeijing 100191China University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Genomics, Proteomics & Bioinformatics》 (基因组蛋白质组与生物信息学报（英文版）)

年 卷 期：2021年第19卷第6期

页      面：949-957页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学] 

基　　金：supported by the National Key R&D Program of China(Grant No.2018YFC0910500). 

主　　题：Macroevolution Prioritization of selective forces Energy efficiency Transcription Translation initiation 

摘      要：Coding regions have complex interactions among multiple selective forces,which are manifested as biases in nucleotide composition.Previous studies have revealed a decreasing GC gradient from the 5′-end to 3′-end of coding regions in various organisms.We confirmed that this gradient is universal in eukaryotic genes,but the decrease only starts from the~25th codon.This trend is mostly found in nonsynonymous(ns)sites at which the GC gradient is universal across the eukaryotic genome.Increased GC contents at ns sites result in cheaper amino acids,indicating a universal selection for energy efficiency toward the N-termini of encoded proteins.Within a genome,the decreasing GC gradient is intensified from lowly to highly expressed genes(more and more protein products),further supporting this hypothesis.This reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns sites.Elevated GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation initiation.Conversely,the GC gradients at four-fold and two-fold synonymous sites vary across species.They could decrease or increase,suggesting different constraints acting at the GC contents of different codon sites in different species.This study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shape the nucleotide sequences,especially efficient energy usage.