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Codon usage of human hepatitis C virus clearance genes in relation to its expression
Pratichi Singh1, Arthi Venkatesan1, Parasuraman Padmanabhan2
1Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India.
Insights
Investigating Hepatitis C virus (HCV) clearance, this study links gene expression to codon bias in liver tissues. Certain genes like CCL5 and APOA2 show higher expression, aiding HCV clearance strategies.
Area of Science:
- Virology
- Genomics
- Bioinformatics
Background:
- Hepatitis C virus (HCV) infection is a major cause of liver cancer and cirrhosis.
- While HCV disease progression is understood, spontaneous HCV clearance mechanisms remain unclear.
Purpose of the Study:
- To investigate the relationship between codon bias and the expression of candidate genes involved in HCV clearance.
- To identify potential genetic markers for spontaneous HCV clearance.
Main Methods:
- Analysis of 112 coding sequences (151,679 codons) for codon bias indices (e.g., relative synonymous codon usage, effective number of codons).
- Assessment of gene expression data using BioGPS to correlate codon bias with differential gene expression in normal and HCV-infected liver tissues.
- Evaluation of base compositions and other codon indices (GC3s, GC12, hydropathicity, aromaticity) to infer selection pressures.
Main Results:
- Codon indices suggest both mutational and translational selection influence candidate genes.
- A significant correlation was found between gene expression in normal and cancerous liver tissues and codon bias (effective number of codons).
- Genes such as CCL5, APOA2, CD28, IFITM1, and TNFSF4 exhibited higher expression correlating with relative codon bias.
Conclusions:
- Codon bias is significantly correlated with the expression of genes involved in HCV clearance.
- Identified genes (CCL5, APOA2, CD28, IFITM1, TNFSF4) are promising candidates for enhancing spontaneous HCV clearance.
- Further research may uncover additional genes contributing to HCV clearance mechanisms.
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.
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