Insights into the evolution of the suppressors of cytokine signalling (SOCS) gene family in vertebrates

The SOCS family are key negative regulators of cytokine and growth factor signalling. Typically 8-17 SOCS genes are present in vertebrate species and 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 additional 15 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 round 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.