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Background  A novel sarcomeric myosin heavy chain gene,  MYH14 , was identified following the completion of the human genome project.  MYH14  contains an intronic microRNA, miR-499, which is expressed in a slow/cardiac muscle specific manner along with its host gene; it plays a key role in muscle fiber-type specification in mammals. Interestingly, teleost fish genomes contain multiple  MYH14  and miR-499 paralogs. However, the evolutionary history of  MYH14  and miR-499 has not been studied in detail. In the present study, we identified  MYH14 /miR-499 loci on various teleost fish genomes and examined their evolutionary history by sequence and expression analyses.    Results  Synteny and phylogenetic analyses depict the evolutionary history of  MYH14 /miR-499 loci where teleost specific duplication and several subsequent rounds of species-specific gene loss events took place. Interestingly, miR-499 was not located in the  MYH14  introns of certain teleost fish. An  MYH14  paralog, lacking miR-499, exhibited an accelerated rate of evolution compared with those containing miR-499, suggesting a putative functional relationship between  MYH14  and miR-499. In medaka,  Oryzias latipes , miR-499 is present where  MYH14  is completely absent in the genome. Furthermore, by using  in situ  hybridization and small RNA sequencing, miR-499 was expressed in the notochord at the medaka embryonic stage and slow/cardiac muscle at the larval and adult stages. Comparing the flanking sequences of  MYH14 /miR-499 loci between torafugu  Takifugu rubripes , zebrafish  Danio rerio , and medaka revealed some highly conserved regions, suggesting that  cis -regulatory elements have been functionally conserved in medaka miR-499 despite the loss of its host gene.    Conclusions  This study reveals the evolutionary history of the  MYH14 /miRNA-499 locus in teleost fish, indicating divergent distribution and expression of  MYH14  and miR-499 genes in different teleost fish lineages. We also found that medaka miR-499 was even expressed in the absence of its host gene. To our knowledge, this is the first report that shows the conversion of intronic into non-intronic miRNA during the evolution of a teleost fish lineage.

bmc evolutionary biology

Evolution of the myosin heavy chain gene MYH14 and its intronic microRNA miR-499: muscle-specific miR-499 expression persists in the absence of the ancestral host gene