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

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

In viruses infecting multicellular animals, such translational biases may lead to increased virion production rates within the infected cell and reduce the accessibility of viruses to the immune response of the host (Bonhoeffer and Nowak, 1994) . However, to the best of our knowledge, the analysis of codon biases of eukaryotic (alongside prokaryotic) viruses compared with their hosts has yet to be undertaken on a large scale. However, related phenomena have been described. Specifically, the codon usage bias in the poxviridae family (dsDNA viruses) was determined by measuring the effective number of codons in the viral proteome. Neither the expression level nor the gene size was shown to be a determinant of the measured codon usage biases. Nonetheless, for most poxviruses, the codon usage was close to the value predicted based on the GC content (Barrett et al, 2006) . Similar results were shown for coronavirus (Gu et al, 2004) and other vertebrate-infecting DNA viruses (Shackelton et al, 2006) . In papillomavirus, the codon bias was attributed to the AT content rather than to host specificity (Zhao et al, 2003) . In the case of retroviruses, it was shown that strong discrimination against CpG sequences directly shapes the codon usage and, as a result, even indirectly restricts the choice of amino acids (Berkhout et al, 2002) . Thus, in general, GC and, specifically, the GC content were thus far found to be the major determinants of codon usage in vertebrate DNA viruses (Shackelton et al, 2006) . It has been found that for many viruses, genome-wide mutational pressures override the selection for specific codons (Jenkins and Holmes, 2003) . Studies of the evolutionary history of viral adaptation propose a cross talk between codon usage, replication mode, genome size, and host range (Koonin et al, 2006) . Furthermore, the observation that there exist both eukaryotic viruses that have adapted their codon usage toward their hosts and those that show little evidence for such adaptation recently prompted the hypothesis that this simply reflects the limited time of the latter for optimization toward their hosts (Barrai et al, 2008) . A contrary view would suggest that the extremely high mutation rates in viruses (especially in RNA viruses) outpace the evolutionary processes of selection that drive such optimization of the virus to the host.