Comparative genomics of hepatitis A virus, hepatitis C virus, and hepatitis E virus provides insights into the evolutionary history of Hepatovirus species

Wassenaar, Trudy M.; Jun, Se-Ran; Robeson, Michael; Ussery, David W.

The genomic variation of HCV is much more extensive than that of HAV. HCV is subdivided in at least 7 major genotypes, with multiple subtypes therein (Simmonds et al., 2005; Smith et al., 2014) . Genetic diversity between the HCV genotypes is about 30%, while subtypes within a given genotype differ by 15%-25% (Hartlage, Cullen, & Kapoor, 2016; Preciado et al., 2014) . The different genotypes roughly coincide with geographical distribution, with genotypes 1, 2, and 3 being globally detected; genotypes 4 and 5 are more prevalent in Africa and the Middle East, and genotype 6 is found in Southeast Asia, as is reviewed elsewhere (Ansaldi et al., 2014) . The RNA-dependent RNA polymerase of HCV lacks proof-reading activity, resulting in a high mutational rate of 10 -5 -10 -4 nucleotides per replication cycle (Duffy, Shackelton, & Holmes, 2008) , thus producing a heterogenic quasi-species population within infected individuals. Estimates for individual nucleotides produced a substitution rate of between 1.40 and 1.72 × 10 −3 ssy (Takahashi et al., 2004) , which is 10 times higher than that of HAV.