Functional divergence of oligoadenylate synthetase 1(OAS1)proteins in Tetrapods  

作　　者：Xiaoxue Wang Jiaxiang Hu Linfei Song Enguang Rong Chenghuai Yang Xiaoyun Chen Juan Pu Honglei Sun Chuze Gao David WBurt Jinhua Liu Ning Li Yinhua Huang 

机构地区：[1]State Key Laboratory for Agrobiotechnology,College of Biology Sciences,China Agricultural University,Beijing 100193,China [2]China Institute of Veterinary Drug Control,Beijing 100081,China [3]Key Laboratory of Animal Epidemiology and Zoonosis,Ministry of Agriculture,College of Veterinary Medicine,China Agricultural University,Beijing 100083,China [4]University of Queensland,St.Lucia,Brisbane,QLD 4072,Australia

出　　处：《Science China(Life Sciences)》2022年第7期1395-1412,共18页中国科学（生命科学英文版）

基　　金：supported by the National Key Research and Development Program of China(2016YFD0500202);the National Natural Science Foundation of China(31772587);the Plan 111(B12008)。

摘　　要：OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.

关 键 词：functional divergence OAS1 molecular evolution PRIMATE palaeognathae 

分 类 号：Q953[生物学—动物学]