Evolutionary analysis of Betaine Homocysteine Methyltransferase (BHMT) and BHMT-2 genes

R.S. Ganu, A.L. Roca, T.A. Garrow, L.B. Schook
Swine in Biomedical Research Conference, July 17-19, 2011, Chicago, IL


The domestic pig is a model organism for research 6n the enzymes betaine homocysteine methyltransferase (BHMT) and BHMT-2, which convert homocysteine to methionine using the substrates betaine and S-methylmethionine, respectively. In order to identify conserved regions that could play a functional role in these proteins, sequences of the BHMT and BHMT-2 genes from 37 species of deuterostomes were compared. The BHMT gene was detected in sea urchin, fish, amphibian, reptile, bird and mammalian genomes. By contrast, the BHMT-2 gene was present only in the genomes of mammals, including monotreme, marsupial and placental species. Thus BHMT gene duplication occurred after the divergence of mammals from other living vertebrates, but prior to the divergence of extant mammalian subclasses. Across mammalian genomes, the BHMT and BHMT-2 genes were located in tandem on the same chromosome, though  in all  mammals the genes differed in regions that code for important  functional  and  structural  motifs.  We identified seven codons that may have been targets of selection. A phylogeny of deuterostome BHMT and BHMT-2 sequences indicated that evolutionary rates were accelerated for BHMT-2 relative to BHMT. Comparing non-synonymous to synonymous mutation ratios across the phylogeny suggested that the highest levels of positive selection had occurred following gene duplication at the base of the mammalian clade. The patterns detected may be of potential relevance to the evolution of mammalian traits.