Birth and death of Mx genes and the presence/absence of genes regulating Mx transcription are correlated with the diversity of anti-pathogenicity in vertebrate species

Gene duplication and amino acid substitution are two types of genetic innovations of antiviral genes in inhibiting the emerging pathogens in different species. Mx proteins are well known for inhibiting negative-stranded RNA viruses and have evolved a number of paralogs or orthologs, showing distinct antiviral activities or capacities within or between species. The presence of upstream genes in the signaling pathway(s) that activates Mx genes (upstream regulators of Mx gene) also exhibits variety across species. The association between the evolution of Mx gene and their upstream regulators and the various antiviral capacities in host species has not been investigated. Herein, we traced the evolution of Mx gene and profiled the gene birth/death events on each branch of the 64 chordate species. We provided additional support that the diversity in gene member and amino acid changes in the different clades is correlated to their various antiviral activities of the species. We identified amino acid substitutions that may lead to the functional divergence between Mx paralogs in rodents. Although the copy number of the Mx gene is conserved in birds, infection by influenza A virus (IAV) results in diverse morbidity rates in different avian species. The evidences of gene interaction in the IAV-induced pathway and the genome analysis performed in this study indicated that the existence of the upstream regulators of Mx gene exhibits variation among different species, particularly in birds. The variation is related to the differences in the expression of Mx genes, resulting in the antiviral specificity and morbidity rates in avian species. We conclude that the antiviral capacity in host species is associated with the variations in the gene number of the Mx gene family and the existence of upstream regulators of Mx gene as well.