ZFIN ID: ZDB-PUB-131024-2
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
Bhuiyan, S.S., Kinoshita, S., Wongwarangkana, C., Asaduzzaman, M., Asakawa, S., and Watabe, S.
Date: 2013
Source: BMC Evolutionary Biology   13: 142 (Journal)
Registered Authors: Asaduzzaman, Md, Kinoshita, Shigeharu, Watabe, Shugo
Keywords: myosin heavy chain, MYH14 (MYH7b), microRNA, miR-499, muscle, muscle fiber-type, teleostei
MeSH Terms:
  • Animals
  • Evolution, Molecular*
  • Fish Proteins/genetics*
  • Fishes/classification
  • Fishes/genetics*
  • Humans
  • Introns
  • Mammals/genetics*
  • MicroRNAs/genetics*
  • Myosin Heavy Chains/genetics*
  • Myosin Type II/genetics
  • Oryzias/genetics
  • Phylogeny
  • Synteny
  • Zebrafish/genetics
PubMed: 24059862 Full text @ BMC Evol. Biol.


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.


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.


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.