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

Abstract

BackgroundA 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.ResultsSynteny 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.ConclusionsThis 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.

MicroRNA-499 Expression Distinctively Correlates to Target Genes sox6 and rod1 Profiles to Resolve the Skeletal Muscle Phenotype in Nile Tilapia

“…1J-M ). Such expression profiles were consistent with reports for mammalian, and embryos of zebrafish and medaka ( Oryzias latipes ) [ 17 – 19 ]. Therefore, we directed our attention to investigate miR-499 features in detail, including target genes, potential regulatory mechanisms of target silencing, and functions in adult Nile tilapia skeletal muscle cells.…”

Evolution of themiR199-214cluster and vertebrate skeletal development

“…For the Dnm/miR199-214 case, we did not find the retention of a duplicated intronic miR with the loss of its host coding-gene, but this type of retention has been described in medaka for a miR499 duplicate in the myh14 gene locus. 62 In zebrafish, an intergenic miR, miR10, ancestrally located within hoxd gene cluster, was retained after the teleost genome duplication despite the loss of all hoxdb protein coding genes. 12 Another interesting feature of miR199-214 gene cluster evolution is the lineagespecific loss of miR duplicates.…”

An integrated analysis revealed different microRNA-mRNA profiles during skeletal muscle development between Landrace and Lantang pigs

“…A trans-homologous interaction between miR-127 and RTL1 was previously found in mouse muscle development 20 , and RTL1 was investigated as a candidate gene in postnatal skeletal muscle growth in callipyge lambs 21 . miR-499 is a muscle-specific miRNA and an intronic miRNA of the myosin heavy chain gene MYH14 that plays a key role in muscle fiber-type specification in mammals 22 . These results indicated the roles of these miRNAs in secondary myofiber formation.…”