柯萨奇A2、A4、A6、A10和A12型病毒的密码子使用偏好性分析  

Codon Usage Bias of Coxsackievirus A2,A4,A6,A10 and A12

作　　者：姚雪 谢彬 韦庆娟 王敏 宗帅 胡弢 高蕾 邢薇佳 王建醒[7] 李娟 YAO Xue;XIE Bin;WEI Qingjuan;WANG Min;ZONG Shuai;HU Tao;GAO Lei;XING Weijia;WANG Jianxing;LI Juan(Key Laboratory of Emerging Infectious Diseases in Universities of Shandong,Shandong First Medical University&Shandong Academy of Medical Sciences,Tai’an 271000,China;Department of Pathogen Biology,School of Clinical and Basic Medical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Ji’nan 271016,China;Tai’an Maternal and Child Health Hospital,Tai’an 271000,China;Ji’nan Children's Hospital,Ji’nan 250022,China;School of Life Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Tai’an 271000,China;School of Public Health,Shandong First Medical University&Shandong Academy of Medical Sciences,Ji’nan 271016,China;Shandong Center for Disease Control and Prevention,Ji’nan 250014,China;Shandong Provincial Hospital Affiliated to Shandong First Medical University,Ji’nan 250021,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)山东省高等学校新发传染病病因流行病学实验室,泰安271000 [2]山东第一医科大学(山东省医学科学院)临床与基础医学院(基础医学研究所)病原生物学系,济南271016 [3]泰安市妇幼保健院,泰安271000 [4]济南市儿童医院,济南250022 [5]山东第一医科大学(山东省医学科学院)生命科学学院,泰安271000 [6]山东第一医科大学(山东省医学科学院)公共卫生与健康管理学院,济南271016 [7]山东省疾病预防控制中心,济南250014 [8]山东第一医科大学附属山东省立医院,济南250021

出　　处：《病毒学报》2023年第1期75-86,共12页Chinese Journal of Virology

基　　金：国家自然科学基金(项目号:81902065),题目:长链非编码RNA-RP11-54O7.17下调干扰素刺激基因15(ISG15)表达促进EV71感染致重症的机制研究;山东省自然科学基金(项目号:ZR2018PH034),题目:柯萨奇病毒A2型分子流行病学特征及对ICR鼠中枢神经系统致病性研究;泰山学者青年专家计划项目。

摘　　要：近年来,引起手足口病的多种柯萨奇病毒逐渐引起人们的关注。为探索柯萨奇病毒进化和变异的潜在机制,本文以柯萨奇A2、A4、A6、A10、A12五种型别病毒的全基因组RNA为研究对象,针对编码结构蛋白的P1区和编码非结构蛋白的P2-P3区基因,分别计算五种型别柯萨奇病毒的核苷酸和氨基酸遗传距离、相对同义密码子使用度(Relative synonymous codon usage,RSCU)、有效密码子数(Effective number of codon,ENC),并进行中性进化分析以及对应分析。结果表明,五种型别柯萨奇病毒的密码子使用均存在多样性,偏倚较弱;与G/C相比,它们的密码子第三位更偏向于使用A/U。ENC-plot分析表明,五种型别柯萨奇病毒P1区受到的突变压力作用均强于P2-P3区。然而,中性进化和对应分析的结果提示,突变压力对这些病毒密码子偏倚的形成仅起着较小的作用,而自然选择在病毒的进化过程中起着更重要的作用。本研究基于密码子水平的生物信息学分析,评估了突变压力和自然选择在柯萨奇A2、A4、A6、A10、A12这五种型别病毒进化中的作用,为深入了解柯萨奇病毒的遗传进化机制提供了理论依据。Multiple coxsackievirus types as pathogens of hand,foot and mouth disease have garnered attention recently.We wished to explore the evolutionary mechanism of coxsackieviruses.Hence,we calculated the genetic distances for nucleotides and amino acids,Relative synonymous codon usage(RSCU)and Effective number of codon(ENC).We also analyzed neutral evolution according to the P1 region encoding structural protein and P2-P3 region encoding non-structural protein of coxsackievirus A2,A4,A6,A10 and A12.Results showed that the codon usage of coxsackievirus A2,A4,A6,A10 and A12 was diverse,with a weak bias.The codon usage frequency of A/U was higher than that of G/C at the third position.Analyses of ENC plots showed that the force of mutation pressure in the P1 region of these coxsackieviruses was stronger than that in the P2-P3region.However,neutral evolution analysis and its correspondence analysis indicated that the role of mutation pressure in driving the codon usage bias was minor,whereas that of natural selection was major.In summary,we evaluated the role of mutation pressure and natural selection in the evolution of coxsackievirus A2,A4,A6,A10 and A12 by analyzing their codon usage pattern using bioinformatics tools,which provided a theoretical basis for further understanding of the evolutionary mechanism of coxsackieviruses.

关 键 词：柯萨奇病毒 密码子使用分析 中性进化 突变压力 

分 类 号：R373.23[医药卫生—病原生物学]