Su Weiheng, Li Xue, Chen Meili, Dai Wenwen, Sun Shiyang, Wang Shuai, Sheng Xin, Sun Shixiang, Gao Chen, Hou Ali, Zhou Yan, Sun Bo, Gao Feng, Xiao Jingfa, Zhang Zhewen, Jiang Chunlai
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China; Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, China.
BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Infect Genet Evol. 2017 Sep;53:212-217. doi: 10.1016/j.meegid.2017.06.004. Epub 2017 Jun 15.
Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) have been considered major pathogens of hand, foot and mouth disease (HFMD) throughout the world for decades. In recent years, coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) have raised attention as two other serious pathogens of HFMD. The present study focused on the synonymous codon usage of four viruses isolated from 2008 to 2015, with particular attention on P1 (encoding capsid proteins) and P2-P3 regions (both encoding non-structural proteins) in the genomic RNA. Relative synonymous codon usage, effective number of codons, neutrality and correspondence were analyzed. The results indicated that these viruses prefer A/T at the third position in codons rather than G/C. The most frequent codons of 4 essential and 2 semi-essential amino acids, as well as a key amino acid of metabolic junctions (Glu) used in the four viruses are also the most frequently used in humans. Effective number of codons (ENC) values indicated weak codon usage bias in all the viruses. Relatively, the force of mutation pressure in the P1 region was found to be stronger than that in the P2-P3 region, and this force in the P1 region of CVA6 and EV71 was stronger than that of CVA10 and A16. The neutrality analysis results implied that mutation pressure plays a minor role in shaping codon bias of these viruses. Correspondence analysis indicated that the codon usage of EV71 strains varied much more than that of other viruses. In conclusion, the present study provides novel and comparative insight into the evolution of HFMD pathogens at the codon level.
几十年来，肠道病毒71型（EV71）和柯萨奇病毒A16型（CVA16）一直被认为是全球手足口病（HFMD）的主要病原体。近年来，柯萨奇病毒A6型（CVA6）和柯萨奇病毒A10型（CVA10）作为手足口病的另外两种严重病原体受到关注。本研究聚焦于2008年至2015年分离出的四种病毒的同义密码子使用情况，尤其关注基因组RNA中的P1区（编码衣壳蛋白）和P2 - P3区（均编码非结构蛋白）。分析了相对同义密码子使用情况、有效密码子数、中性和对应性。结果表明，这些病毒在密码子的第三位更倾向于A/T而非G/C。四种病毒中使用的4种必需氨基酸和2种半必需氨基酸以及代谢连接点的一个关键氨基酸（Glu）的最常用密码子在人类中也是最常用的。有效密码子数（ENC）值表明所有病毒的密码子使用偏好较弱。相对而言，发现P1区的突变压力比P2 - P3区更强，并且CVA6和EV71的P1区的这种压力比CVA10和A16更强。中性分析结果表明，突变压力在塑造这些病毒的密码子偏好方面起次要作用。对应分析表明，EV71毒株的密码子使用变化比其他病毒大得多。总之，本研究在密码子水平上为手足口病病原体的进化提供了新的比较性见解。
