The comparative genomics and physiology of myostatin
Creators: name: Garikipati, Dilip Kumar
Publisher: name: Washington State University
Year: 2007
Subjects: Muscles -- Growth -- Regulation

description: Myostatin is well described as a negative regulator of skeletal muscle growth in
description: mammals and myostatin-null animals possess a “double muscle” phenotype. Recent
description: attempts to produce a similar phenotype in fish have failed. Myostatin biology in fishes
description: significantly differs from that in mammals and the presence of multiple myostatin genes
description: suggests possible functional divergence. Two new rainbow trout myostatin genes were
description: identified in addition to the available MSTN-1a and -1b genes. Phylogenetic analyses
description: grouped the new genes into the myostatin-2 clade supporting previous analyses. The
description: genomic structure of all four rainbow trout myostatin genes, rtMSTN-1a, -1b, -2a and -
description: 2b, was conserved with three exons, two relatively short introns and conserved
description: exon/intron boundaries that for the most part were conserved among all vertebrate
description: homologs. Subsequence analysis of the promoter regions identified several putative
description: myogenic elements, although the structure of each promoter was unique and was
description: reflected in the differential gene expression. The rtMSTN-2b gene contained two inframe stop codons suggesting that it is a pseudogene. The embryonic expression of
description: rtMSTN-1 genes was similar, however, rtMSTN-1a was highly expressed compared to
description: rtMSTN-1b gene and rtMSTN-2a was not significantly expressed throughout development. All the myostatin genes were expressed in various tissues of rainbow trout, although the expression level varied with gene and tissue. Alternative splicing was
description: detected with both rtMSTN-2 transcripts and occurred in a manner that limited mature
description: rtMSTN-2a transcripts to the brain and contributed to rtMSTN-2b pseudogenization. The
description: tissue and gene specific processing, differential gene expression and pseudogenization of rtMSTN-2b likely represent compensatory and adaptive response to tetraploidization. The ubiquitous expression of at least two rtMSTN genes in all tissues surveyed suggests that myostatin’s actions may be pleiotropic in fish. Recent studies, however, suggest that myostatin may also influence tissues other than skeletal muscle in mammals as well. Therefore, we determined the effect of myostatin on cardiomyoblasts. Myostatin suppressed both basal and stimulated proliferation of these cells and also inhibited differentiation. These data indicate that myostatin may play a wider role than previously believed as it similarly regulates skeletal and cardiac muscle in mammals. Knowledge from the studies with rainbow trout will help explain the underlying mechanisms of functional divergence while the cardiomyoblast studies may help design novel therapeutics for treating myocardial infarction. Together, these studies highlight the value of a comparative approach to understanding the evolution and physiology of this dynamic gene family.