Divergent evolution of the myosin heavy chain gene family in fish and tetrapods: evidence from comparative genomic analysis

2007 ◽  
Vol 32 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Daisuke Ikeda ◽  
Yosuke Ono ◽  
Phil Snell ◽  
Yvonne J. K. Edwards ◽  
Greg Elgar ◽  
...  

Myosin heavy chain genes ( MYHs) are the most important functional domains of myosins, which are highly conserved throughout evolution. The human genome contains 15 MYHs, whereas the corresponding number in teleost appears to be much higher. Although teleosts comprise more than one-half of all vertebrate species, our knowledge of MYHs in teleosts is rather limited. A comprehensive analysis of the torafugu ( Takifugu rubripes) genome database enabled us to detect at least 28 MYHs, almost twice as many as in humans. RT-PCR revealed that at least 16 torafugu MYH representatives (5 fast skeletal, 3 cardiac, 2 slow skeletal, 1 superfast, 2 smooth, and 3 nonmuscle types) are actually transcribed. Among these, MYH M743-2 and MYH M5 of fast and slow skeletal types, respectively, are expressed during development of torafugu embryos. Syntenic analysis reveals that torafugu fast skeletal MYHs are distributed across five genomic regions, three of which form clusters. Interestingly, while human fast skeletal MYHs form one cluster, its syntenic region in torafugu is duplicated, although each locus contains just a single MYH in torafugu. The results of the syntenic analysis were further confirmed by corresponding analysis of MYHs based on databases from Tetraodon, zebrafish, and medaka genomes. Phylogenetic analysis suggests that fast skeletal MYHs evolved independently in teleosts and tetrapods after fast skeletal MYHs had diverged from four ancestral MYHs.

1991 ◽  
Vol 266 (36) ◽  
pp. 24613-24620
Author(s):  
A. Subramaniam ◽  
W.K. Jones ◽  
J. Gulick ◽  
S. Wert ◽  
J. Neumann ◽  
...  

2004 ◽  
Vol 24 (19) ◽  
pp. 8705-8715 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Steve M. Helmke ◽  
Stephen J. Langer ◽  
M. Benjamin Perryman ◽  
Michael Bristow ◽  
...  

ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.


Sign in / Sign up

Export Citation Format

Share Document