ABSTRACT
We have recently determined the complete nucleotide sequences of the cardiac alpha- and beta-myosin heavy chain (MyHC) genes from both human and Syrian hamster. These genomic sequence data were used to study the molecular evolution of the cardiac MyHC genes. Between the alpha- and beta-MyHC genes, multiple gene conversion events were detected by (1) maximum parsimony tree analyses, (2) synonymous substitution analyses, and (3) detection of pairwise identity of intron sequences. Approximately half of the 40 cardiac MyHC exons have undergone concerted evolution through the process of gene conversion with the other half undergoing divergent evolution. Gene conversion occurred more often in exons encoding the alpha-helical myosin rod domain than in the globular head domain, and an apparent directional bias was also observed, with transfer of genetic material occurring more often from beta to alpha.
Subject(s)
Mammals/genetics , Myocardium/chemistry , Myosin Heavy Chains/genetics , Animals , Cricetinae , Exons/genetics , Gene Conversion , Genes , Humans , Mesocricetus/genetics , Rats/genetics , Sequence Homology, Nucleic Acid , Species SpecificityABSTRACT
The human myocardium expresses two cardiac myosin heavy chain (MyHC) isoforms, alpha and beta, that exist in tandem array on chromosome 14q12. We have previously sequenced the entire human cardiac beta-MyHC gene and now report the complete nucleotide sequence of the human cardiac alpha-MyHC, encompassing 26,159 bp as well as the entire 4484-bp 5'-flanking intergenic region. The gene (MYH6) consists of 39 exons, 37 of which contain coding information. The 5'-untranslated region is split into 3 exons, with the third exon containing the AUG translation initiation codon. With the exception of the 13th intron of the human cardiac beta-MyHC, which is not present within the alpha-isogene, all exon/intron boundaries are conserved. Conspicuous sequence motifs contained within the alpha-MyHC gene include four Alu repeats, a single (GT)n element, and a homopurine-homopyrimidine tract containing 23 GAA repeating units followed by 10 GAG repeating units. Comparison of the encoded amino acid sequence with a previously reported human alpha-MyHC cDNA sequence reveals several potential polymorphisms.
