Synonymous codon usage analysis of hand, foot and mouth disease viruses: A comparative study on coxsackievirus A6, A10, A16, and enterovirus 71 from 2008 to 2015.

Weiheng Su, Xue Li, Meili Chen, Wenwen Dai, Shiyang Sun, Shuai Wang, Xin Sheng, Shixiang Sun, Chen Gao, Ali Hou, Yan Zhou, Bo Sun, Feng Gao, Jingfa Xiao, Zhewen Zhang, Chunlai Jiang
Author Information
  1. Weiheng Su: 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.
  2. Xue Li: 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.
  3. Meili Chen: 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.
  4. Wenwen Dai: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
  5. Shiyang Sun: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
  6. Shuai Wang: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
  7. Xin Sheng: 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.
  8. Shixiang Sun: 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.
  9. Chen Gao: 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.
  10. Ali Hou: 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.
  11. Yan Zhou: 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.
  12. Bo Sun: 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.
  13. Feng Gao: 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.
  14. Jingfa Xiao: 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.
  15. Zhewen Zhang: 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. Electronic address: zhangzw@big.ac.cn.
  16. Chunlai Jiang: 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. Electronic address: jiangcl@jlu.edu.cn.

Abstract

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.

Keywords

MeSH Term

Amino Acids
Capsid Proteins
Codon
Enterovirus A, Human
Gene Expression
Genetic Code
Genome, Viral
Hand, Foot and Mouth Disease
Humans
Sequence Analysis, DNA
Viral Nonstructural Proteins

Chemicals

Amino Acids
Capsid Proteins
Codon
Viral Nonstructural Proteins