Differential Loss of OAS Genes Indicates Diversification of Antiviral Immunity in Mammals.

One of the main mechanisms of inducing an antiviral response depends on 2'-5'-oligoadenylate synthetases (OAS), which sense double-stranded RNA in the cytoplasm and activate RNase L. Mutations leading to the loss of functional and genes have been identified as important modifiers of the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we performed comparative genomics to search for inactivating mutations of genes in other species of mammals and to establish a model for the diversifying evolution of the gene family. We found that a recombination of the and () loci has led to the loss of in camelids, which also lack . Both paralogs of and are absent in Asian pangolins. An evolutionarily ancient paralog, which we tentatively name , has been lost in pangolins, bats and humans. A previously unknown gene, tentatively named , is present in Yangochiroptera, a suborder of bats. These differences in the gene repertoire may affect innate immune responses to coronaviruses and other RNA viruses.