Identification of TGF-β, inhibin βA and follistatin paralogs in the rainbow trout genome.

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Since their initial discovery, TGF-β superfamily members have been considered multifunctional growth and differentiation factors in many cell types. Various studies have clearly demonstrated the key roles of specific TGF-β members in muscle growth, including myostatin and inhibin as well as genes, such as follistatin. By binding to TGF-β members, follistatin prevents TGF-β from binding to its receptors and thus neutralizes its activity. Here, we report the identification of the gene sequences of four TGF-β isoforms and three paralogs of TGF-β1, which we called TGF-β1a, TGF-β1b and TGF-β1c, four sequences of inhibin βA paralogs; and two sequences of follistatin paralogs from rainbow trout. A phylogenetic analysis clearly indicated the existence of four monophyletic clades, corresponding to TGF-β1, -β2, -β3 and -β6. Based on their sequence identity TGF-β1a and -β1c are grouped together, whereas TGF-β1b appears more divergent even though it is grouped within the TGF-β1 clade. Alignments and phylogenetic analyses showed that the protein sequences of TGF-β, inhibin βA and follistatin are extremely well conserved (>90%) relative to each other; however, their regulation and expression patterns are different. TGF-β2 and -β3 showed the most abundant expression in muscle and were the main TGF-β members expressed in this tissue. Follistatin and inhibin βA paralogs were expressed in all tissues examined but with different patterns. Our identification of multiple copies of TGF-β, inhibin βA and follistatin with different expression patterns suggests non-redundant functions for these paralogs in rainbow trout.