Insights into the Evolution of the Suppressors of Cytokine Signaling (SOCS) Gene Family in Vertebrates.

Bei Wang,Tiehui Wang,Christopher J Secombes,Eakapol Wangkahart,Yoko Satta

doi:10.1093/molbev/msy230

Abstract

The SOCS family are key negative regulators of cytokine and growth factor signaling. Typically, 8–17 SOCS genes are present in vertebrate species with eight known in mammals, classified as type I (SOCS4–7) and type II (CISH and SOCS1–3) SOCS. It was believed that the type II SOCS were expanded through the two rounds of whole genome duplication (1R and 2R WGDs) from a single CISH/SOCS1–3 precursor. Previously, 12 genes were identified in rainbow trout but here we report 15 additional loci are present, and confirm 26 of the genes are expressed, giving rainbow trout the largest SOCS gene repertoire identified to date. The discovery of the additional SOCS genes in trout has led to a novel model of SOCS family evolution, whereby the vertebrate SOCS gene family was derived from CISH/SOCS2, SOCS1/SOCS3, SOCS4/5, SOCS6, and SOCS7 ancestors likely present before the two WGD events. It is also apparent that teleost SOCS2b, SOCS4, and SOCS5b molecules are not true orthologues of mammalian SOCS2, SOCS4, and SOCS5, respectively. The rate of SOCS gene structural changes increased from 2R vertebrates, to 4R rainbow trout, and the genes with structural changes show large differences and low correlation coefficient of expression levels relative to their paralogues, suggesting a role of structural changes in expression and functional diversification. This study has important impacts in the functional prediction and understanding of the SOCS gene family in different vertebrates, and provides a framework for determining how many SOCS genes could be expected in a particular vertebrate species/lineage.

Highlights

The suppressors of cytokine signaling (SOCS) family of proteins are key negative regulators of cytokine and growth factor signaling
This study provides a framework for determining how many SOCS genes could be expected in a particular vertebrate species/lineage, and proposes a new model for SOCS gene evolution
Our bioinformatics analysis suggests that 2R vertebrates may possess up to 12 and 3R teleosts up to 15 SOCS family genes, with additional genes potentially arising from species/lineage-specific gene duplication

Summary

Introduction

The suppressors of cytokine signaling (SOCS) family of proteins are key negative regulators of cytokine and growth factor signaling Since their discovery in the late 1990s, these small intracellular proteins have been characterized as regulatory cornerstones of intracellular signaling (Kazi et al 2014; Linossi and Nicholson 2015; Jiang et al 2017). The SOCS family are characterized by a highly conserved C-terminal SOCS box motif, a central Src homology 2 (SH2) domain and an adjacent ahelical extension, termed the extended SH2-subdomain (ESS), and an N-terminal region that varies in sequence and length across the family (Delgado-Ortega et al 2011; Linossi and Nicholson 2015; Duncan et al 2017). SOCS4–7 contain an extensive N-terminal region (termed the type I subfamily) that distinguishes them from SOCS1–3 and CISH (type II subfamily; Jin et al 2008)

Methods

Results

Discussion

Conclusion