Expansion and molecular evolution of the interferon-induced 2 '-5 ' oligoadenylate synthetase gene family

The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze th e polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block viral replic ation at the level of mRNA degradation. A molecular evolutionary analysis o f available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The m odern mammalian 2'-5'OAS genes underwent successive gene duplication events resulting in three size classes of enzymes, containing one, two, or three homologous domains. Expansion of the OAS gene family occurred by whole-gene duplications to increase gene content and by domain couplings to produce t he multidomain genes. Evolutionary analyses show that the 2'-5'OAS genes in rodents underwent gene duplications as recently as 11 MYA and predict the existence of additional undiscovered OAS genes in mammals.