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.

Nevertheless, nonpreferred third bases can slow down the translation machinery, which presumably allows better protein folding of the capsid protein (Pintó et al., 2018) . Costafreda and coworkers have shown that selection for deoptimized HAV codons was related to transcription efficiency, antigenicity of capsid protein, plaque size, and survival rates of virions (Costafreda et al., 2014) . However, it is hard to envisage how this situation might have evolved when an ancestor of HAV had a codon usage that was better adapted to the mammalian host. In general, the direction of virus evolution would be toward more efficient, not toward less efficient translation and replication in a given host, as it would result in more (or more rapid) virion production. Moreover, if the selective pressure would mostly apply to optimal folding of the capsid protein, only that coding region of the genome would depend on using deoptimized codons, but the virus proteome is consistently using codons that human cells do not prefer, over its complete ORF length This is shown in Appendix Figure A2 . We consider the most likely explanation for the current codon usage of HAV that it is a remnant of an ancestor virus that replicated in a host with a codon usage preference different to that of humans.