Evolutionary pathways of the PA genes of influenza A viruses

Nucleotide sequences of the PA genes of influenza A viruses, isolated from a variety of host species, were analyzed to determine the evolutionary pathways of these genes and the host specificity of the genes. Results of maximum parsimony analysis of the nucleotide sequences indicate at least five lineages for the PA genes. Those from human strains represent a single lineage, whereas the avian genes appear to have evolved as two lineages--one comprising genes from many kinds of birds (e.g., chickens, turkeys, shorebirds, and ducks) and the other comprising only genes from gulls. H3N2 swine influenza virus PA genes are closely related to the currently circulating duck virus PA gene. By contrast, the H1N1 swine and equine virus PA genes appear to have evolved along independent lineages. Comparison of predicted amino acid sequences disclosed 10 amino acid substitutions in the PA proteins of all avian and H3N2 swine viruses that distinguished them from human viruses. The H1N1 swine viruses seem to be chimeras between human and avian viruses and they contain 8 amino acids not shared by other viruses. The equine viruses also appear to show their own amino acid substitutions. These findings indicate that the PA genes of influenza A viruses have evolved in different pathways defined by apparently unique amino acid substitutions and host specificities. They also indicate that influenza A viruses have been transmitted from avian to mammalian species.