Evolution of the vertebrate insulin receptor substrate (Irs) gene family

BMC Evolutionary Biology

Research Article

Ahmad Al-Salam¹  David M. Irwin² 

[1] Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, M5S 1A8, Toronto, ON, Canada;Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King’s College Circle, M5S 1A8, Toronto, ON, Canada;Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada;

关键词: Insulin receptor substrate;    Gene duplication;    Protein evolution;    Episodic evolution;    Phylogeny;    Vertebrate;    Pseudogene;   

DOI  :  10.1186/s12862-017-0994-z

 received in 2017-03-03, accepted in 2017-06-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundInsulin receptor substrate (Irs) proteins are essential for insulin signaling as they allow downstream effectors to dock with, and be activated by, the insulin receptor. A family of four Irs proteins have been identified in mice, however the gene for one of these, IRS3, has been pseudogenized in humans. While it is known that the Irs gene family originated in vertebrates, it is not known when it originated and which members are most closely related to each other. A better understanding of the evolution of Irs genes and proteins should provide insight into the regulation of metabolism by insulin.ResultsMultiple genes for Irs proteins were identified in a wide variety of vertebrate species. Phylogenetic and genomic neighborhood analyses indicate that this gene family originated very early in vertebrae evolution. Most Irs genes were duplicated and retained in fish after the fish-specific genome duplication. Irs genes have been lost of various lineages, including Irs3 in primates and birds and Irs1 in most fish. Irs3 and Irs4 experienced an episode of more rapid protein sequence evolution on the ancestral mammalian lineage. Comparisons of the conservation of the proteins sequences among Irs paralogs show that domains involved in binding to the plasma membrane and insulin receptors are most strongly conserved, while divergence has occurred in sequences involved in interacting with downstream effector proteins.ConclusionsThe Irs gene family originated very early in vertebrate evolution, likely through genome duplications, and in parallel with duplications of other components of the insulin signaling pathway, including insulin and the insulin receptor. While the N-terminal sequences of these proteins are conserved among the paralogs, changes in the C-terminal sequences likely allowed changes in biological function.

【 授权许可】

CC BY   
© The Author(s). 2017