Molecular Evolution Studies on Hepatitis C Virus based on NS5B Region

Hepatitis C Virus (HCV) infection is a major health problem that leads to cirrhosis and hepatocellular carcinoma. World over, more than 270-300 million people are estimated to be infected with the virus. HCV is a positive sense single stranded RNA virus and replicates within the cytoplasm of the hepatocyte using its own RNA dependent RNA polymerase (RdRp). RdRp does not have proof reading capacity, and hence generates mutants of the virus, resulting in a chronic infection, which ultimately ends in hepatocellular carcinoma. Such mutations have given rise to several genotypes, subtypes, strains and variants with significant difference in disease outcomes. The mutation rate varies among genotypes, subtypes, strains or even in different sites of the genome. Yet, the extent of heterogeneity is usually moderate, so that estimates of the time of divergence can be computed. The evolution of variants seems to be influenced by the genetic make-up and the immune response of the host and has geographical significance. Here we used phylogenetic analysis and Computational molecular dating techniques to conclude that the ancestral genotype is 7a and that it originated in Canada 363 years ago. Molecular dating was based on the fact that the rate of mutation across all evolutionary lineages is constant over time. Surprisingly, our analyses show that genotype 1d isolated from Canada 5 is the most recent with an evolutionary date of just 33 years. It is evident that HCV is still an emerging virus and demographical parameters seem to have a very strong influence in its evolution. We believe that this emphasizes the need for developing drugs that are customized to act against strains that evolve and become geographically endemic.