Accumulated metagenomic studies reveal recent migration, whole genome evolution, and undiscovered diversity of orthomyxoviruses

Metagenomic studies have uncovered many novel viruses by looking beyond hosts of public health or economic interest. However, the resulting viral genomes are often incomplete, and analyses largely characterize the distribution of viruses over their dynamics. Here, we integrate accumulated data from metagenomic studies to reveal geographic and evolutionary dynamics in a case study ofOrthomyxoviridae, the RNA virus family that includes influenza virus. First, we use sequences of the orthomyxovirid Wǔhàn mosquito virus 6 to track the migrations of its host. We then look at orthomyxovirus genome evolution, finding gene gain and loss across members of the family, especially in the surface proteins responsible for cell and host tropism. We find that the surface protein of Wǔhàn mosquito virus 6 exhibits accelerated non-synonymous evolution suggestive of antigenic evolutioni.e. vertebrate infection, and belongs to a wider quaranjavirid group bearing highly diverged surface proteins. Finally we quantify the progress of orthomyxovirus discovery and forecast that many divergedOrthomyxoviridaemembers remain to be found. We argue that continued metagenomic studies will be fruitful for understanding the dynamics, evolution, ecology of viruses and their hosts, regardless of whether novel viruses are identified or not, as long as study designs allowing for the resolution of complete viral genomes are employed.