Abstract
BackgroundMost fishes possess two paralogs for myostatin, a muscle growth inhibitor, while salmonids are presumed to have four: mstn1a, mstn1b, mstn2a and mstn2b, a pseudogene. The mechanisms responsible for preserving these duplicates as well as the depth of mstn2b nonfunctionalization within the family remain unknown. We therefore characterized several genomic clones in order to better define species and gene phylogenies.ResultsGene organization and sequence conservation was particularly evident among paralog groupings and within salmonid subfamilies. All mstn2b sequences included in-frame stop codons, confirming its nonfunctionalization across taxa, although the indels and polymorphisms responsible often differed. For example, the specific indels within the Onchorhynchus tshawytscha and O. nerka genes were remarkably similar and differed equally from other mstn2b orthologs. A phylogenetic analysis weakly established a mstn2b clade including only these species, which coupled with a shared 51 base pair deletion might suggest a history involving hybridization or a shared phylogenetic history. Furthermore, mstn2 introns all lacked conserved splice site motifs, suggesting that the tissue-specific processing of mstn2a transcripts, but not those of mstn2b, is due to alternative cis regulation and is likely a common feature in salmonids. It also suggests that limited transcript processing may have contributed to mstn2b nonfunctionalization.ConclusionsPrevious studies revealed divergence within gene promoters while the current studies provide evidence for relaxed or positive selection in some coding sequence lineages. These results together suggest that the salmonid myostatin gene family is a novel resource for investigating mechanisms that regulate duplicate gene fate as paralog specific differences in gene expression, transcript processing and protein structure are all suggestive of active divergence.
Highlights
Most fishes possess two paralogs for myostatin, a muscle growth inhibitor, while salmonids are presumed to have four: mstn1a, mstn1b, mstn2a and mstn2b, a pseudogene
A better understanding of myostatin gene structure and phylogenies among other salmonids would help explain fundamental mechanisms that influence duplicate gene fate and control their fixation and maintenance, which in turn enables the functional diversification of genes and genomes [17]
Comparative Mapping and Gene Organization The basic organization of each salmonid myostatin paralog is highly conserved as each gene contains three exons (Figure 1)
Summary
Most fishes possess two paralogs for myostatin, a muscle growth inhibitor, while salmonids are presumed to have four: mstn1a, mstn1b, mstn2a and mstn2b, a pseudogene. The myokine appears to inhibit muscle progenitor cell proliferation in all systems, studies with mammalian cell lines and primary fish myosatellite cells suggest it either inhibits or stimulates differentiation, respectively [7,8,9,10,11]. This discrepancy is partially explained by culture conditions and by the immortalized phenotype of cell lines. Each paralog is differentially expressed in rainbow trout and the mstn transcripts are alternatively processed in a way that contributes to the nonfunctionalization of mstn2b and to the tissue-specific actions of mstn2a. A better understanding of myostatin gene structure and phylogenies among other salmonids would help explain fundamental mechanisms that influence duplicate gene fate and control their fixation and maintenance, which in turn enables the functional diversification of genes and genomes [17]
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