Codon usage of human hepatitis C virus clearance genes in relation to its expression

J Cell Biochem. 2020 Jan;121(1):534-544. doi: 10.1002/jcb.29290. Epub 2019 Jul 16.

Abstract

Hepatitis C virus (HCV) infection is among the leading causes of hepatocellular carcinoma and liver cirrhosis globally, with a high economic burden. The disease progression is well established, but less is known about the spontaneous HCV infection clearance. This study tries to establish the relationship between codon biasness and expression of HCV clearance candidate genes in normal and HCV infected liver tissues. A total of 112 coding sequences comprising 151 679 codons were subjected to the computation of codon indices, namely relative synonymous codon usage, an effective number of codon (Nc), frequency of optimal codon, codon adaptation index, codon bias index, and base compositions. Codon indices report of GC3s, GC12, hydropathicity, and aromaticity implicates both mutational and translational selection in the candidate gene set. This was further correlated with the differentially expressed genes among the selected genes using BioGPS. A significant correlation is observed between the gene expression of normal liver and cancerous liver tissues with codon bias (Nc). Gene expression is also correlated with relative codon bias values, indicating that CCL5, APOA2, CD28, IFITM1, and TNFSF4 genes have higher expression. These results are quite encouraging in selecting the high responsive genes in HCV clearance. However, there could be additional genes which could also orchestrate the clearance role with the above mentioned first line of defensive genes.

Keywords: HCV clearance candidate genes; codon usage bias; gene expression; mutational pressure; natural selection.

MeSH terms

  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Apolipoprotein A-II / genetics
  • Apolipoprotein A-II / metabolism
  • Biomarkers / metabolism*
  • CD28 Antigens / genetics
  • CD28 Antigens / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Codon Usage / genetics*
  • Hepacivirus / genetics*
  • Hepacivirus / pathogenicity*
  • Hepatitis C / genetics
  • Hepatitis C / virology*
  • Humans
  • OX40 Ligand / genetics
  • OX40 Ligand / metabolism
  • Viral Load*

Substances

  • APOA2 protein, human
  • Antigens, Differentiation
  • Apolipoprotein A-II
  • Biomarkers
  • CCL5 protein, human
  • CD28 Antigens
  • Chemokine CCL5
  • OX40 Ligand
  • TNFSF4 protein, human
  • leu-13 antigen