Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences

Bahir, Iris; Fromer, Menachem; Prat, Yosef; Linial, Michal

In this paper, we set out to determine whether, despite the enormous diversity among viruses, a high-level, generalized trend of adaptation of viruses toward their hosts can be observed. To this end, we provide a strict virus-to-host mapping using a non-redundant set of representative viruses and hosts, ranging from human to bacteria. We develop a statistical framework for the unbiased assessment of the mutual pairwise distances between all viruses and all recognized hosts. To test the hypothesis of general molecular adaptation of a virus toward its hosts, we focus on codon usage and amino acid preferences within groups of viruses that are unified at varying taxonomical granularities. We observe that all bacteriophages are strongly tuned to match their unique hosts and this correspondence is also evident in their GC contents. However, somewhat surprisingly, viruses that infect humans resemble all mammalian hosts equally, and this similarity even extends to aves and several insects. This observation does not hold for viruses of other mammals, despite a strong similarity among the codon usages of most mammals. Finally, we show that viral selection of codon usage toward that of the host has not occurred uniformly for all proteins of the virus, but it is mainly dominated by the set of proteins expressed in high abundance. The implications of these observations for viral evolution and on the potential for zoonotic epidemics are discussed.