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 study, we set out to analyze the overall potential adaptability of known virus families by using the complete set of virus representatives that reflect the current knowledge of all major viruses. Clearly, our analyses are strongly dependent on the correct mapping of viruses to their hosts. We analyzed 122 viruses at the higher taxonomical levels and 64 viruses at the host-species level, where each such virus represents a different viral genus (Table I; Supplementary Table S2 ). By the strict mapping of a set of 30 virus genera that exclusively infect 30 different hosts, we limited the set of viruses and often remained with only one or very few representatives for a unique host. It is possible that the set of viruses that have a restricted range of hosts is skewed. They may reflect (i) poorly studied cases, which leads to partial information regarding the virus and its hosts; and (ii) cases where the dependency on virus-host pair is stronger because of a specific molecular barrier that restricts the host range. We cannot separate these two instances, but for many cases the restricted host assignment is supported by a large body of literature. For example, the observed overwhelming similarity in amino acid distributions and in the codon usage among viruses infecting the tomato, lettuce, rice, and arabidopsis plants ( Figure 4 ) seems more likely to be a result of incomplete annotation in the viral database, where each of these viruses overlap and, in reality, infect the other plants but are simply not yet annotated as such. This is in accord with the current view of plant-infecting viruses (Roossinck, 1997) . Although the statistical power for some analyses may be affected by this 'reduction to representatives,' we argue that the trends observed in this study hold and will be further substantiated when additional viruses with accurate annotations become available. We analyzed a representative set of viruses irrespective of their mode of replication according to a partition to the 7 standard classes (Melnick, 1972) that are indicated by I-VII. Note that host specificity does not determine the class. For example, although most viruses that infect humans (Supplementary Table S1 ) belong to class I, human-infecting viruses are represented in all other classes, including the well-known health-threatening viruses, such as the Coronavirus family (SARS, class IV), Lentivirus (AIDS virus, class VI), and Ebola virus (class V). The genomic structures, nucleotide composition, replicative mode, replication time, and rates of mutation in the different classes are estimated to show great differences, where, for example, RNA viruses mutate much faster than other groups. Despite these differences, the analysis of humaninfecting viruses based on this classification showed that the observed adaptation of human viruses characterizes viruses from a broad range of life cycles and replication modes.