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

Abstract

The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze the polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block vital replication at the level of mRNA degradation. A molecular evolutionary analysis of available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The modem 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 the 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.