Structure and function of the cardiac myosin heavy chain genes in Syrian hamster
[Thesis]
R. Wang
C. C. Lien
University of Toronto (Canada)
1994
298
Ph.D.
University of Toronto (Canada)
1994
I have isolated and completely sequenced a continuous 66,315 bp nucleotide sequence encompassing the entire cardiac usd\alphausd- and usd\betausd-MyHC genes of the Syrian hamster. This is the first complete sequencing of small mammalian cardiac MyHC genes at the genomic level. Structural characterization revealed that the two genes are aligned in tandem, with the usd\betausd-MyHC gene upstream, separated by a 4,035 bp intergenic region. The usd\betausd-gene is 21,732 bp in length and contains 41 exons which encode a predicted transcript of 6,084 nt that may be translated into a 1,934 residue polypeptide of 222,917 Da. The usd\alphausd-gene is 26,130 bp in length and contains 39 exons that code for a transcript of 6,085 nt that can be translated into a deduced 1,939 residue polypeptide of 223,664 Da. Coding sequences of the usd\alphausd- and usd\betausd-MyHC genes are highly conserved between the Syrian hamster and human, except that in the 5 untranslated region of the Syrian hamster usd\betausd-MyHC gene, I identified an extra exon. Expression of the orthologous genes between the two species, however, are differentiated. In addition, I found a reappearance of ventricular expression of the Syrian hamster usd\betausd-MyHC gene at 60 days of age. Comparison between the Syrian hamster and human revealed many structural differences that could be associated with differential expression of these genes. Consensus B1 and B2 retroposonal sequences of the Syrian hamster were obtained. They are found clustered in the distal region of the 5 flanking region of the usd\betausd-MyHC gene and within the usd\alphausd-MyHC gene. The usd\alphausd-MyHC gene is also redundant with various forms of repetitive sequences. Molecular evolution was studied by identifying multiple intrachromosomal gene conversions between the usd\alphausd- and usd\betausd-MyHC genes. This is the first time that concrete genomic data show the concerted evolution of the cardiac MyHC genes. Meanwhile, multiple gene conversions between the human cardiac usd\alphausd- and usd\betausd-MyHC genes were also identified. A general trend was found to be that gene conversion took place more frequently in regions coding for the MyHC tail than those coding for head portion of the MyHC. A tendency of gene conversion from usd\betausd-MyHC gene to usd\alphausd-MyHC gene was also noticed.