Genome-wide analysis for identification of adaptive diversification between hepatitis C virus subtypes 1a and 1b

Abstract

Hepatitis C virus (HCV) is a major cause of liver disease and has been estimated to infect approximately 2%–3% of the world’s population. HCV genotype 1 is the subject of intense research and clinical investigations because of its worldwide prevalence and poor access to treatment for patients in developing countries and marginalized populations. The predominant subtypes 1a and 1b of HCV genotype 1 present considerable differences in epidemiological features. However, the genetic signature underlying such phenotypic functional divergence is still an open question. Here, we performed a genome-wide evolutionary study on HCV subtypes 1a and 1b. The results show that adaptive selection has driven the diversification between these subtypes. Furthermore, the major adaptive divergence-related changes have occurred on proteins E1, NS4B, NS5A, and NS5B. Structurally, a number of adaptively selected sites cluster in functional regions potentially relevant to (i) membrane attachment and (ii) the interactions with viral and host cell factors and the genome template. These results might provide helpful hints about the molecular determinants of epidemiological divergence between HCV 1a and 1b.