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.

All three viral species are subdivided into genotypes and subtypes therein, based on hypervariable regions of their genomes. For HAV, three genotypes that infect humans (I, II and II, each with subtypes A and B) are recognized, and these belong to a single serotype. Three more genotypes are specific to the simian host (Costa-Mattioli et al., 2003) , while a previously described genotype VII is reclassified as IIB. A substitution rate of 9.76 × 10 -4 substitutions per site per year (ssy) was calculated, based on complete VP1 sequences from French genotype IA isolates (Moratorio et al., 2007) , but this may be an overestimate, as an analysis of complete genome sequences from multiple countries produced an estimate of 1.00 × 10 -4 ssy (Kulkarni, Walimbe, Cherian, & Arankalle, 2009 ). Thus, the range is likely to be around one in ten thousand substitutions per site per year, or roughly one or two substitutions per viral genome per year. This reflects the slow evolutionary rate of this virus. A last common ancestor of human HAV and the simian genotypes was estimated to have existed between 1,250 and 3,500 years ago (Kulkarni et al., 2009 ).