Developmental and evolutionary analysis of betaine homocysteine methyltransferase genes
Abstract
Methionine (Met) is an essential amino acid because mammals cannot synthesize homocysteine. Betaine-homocysteine methyltransferase (BHMT) and BHMT-2 methylate homocysteine to form methionine using betaine and S-methylmethionine, respectively. Betaine is produced de novo from choline and is also found in the diet, whereas S-methylmethionine is only made in plants and fungi and so must be obtained from the diet. These enzyme activities are only be detected in the liver of adult rodents, but in adult humans and pigs, these activities are found in both the liver and kidney cortex. Since both pigs and humans are omnivores and share the same pattern of BHMT and BHMT-2 expression, the pig represents an excellent model for studying the physiological roles of these enzymes in human biology. As a prelude to investigating the influence of diet and development on the expression of porcine BHMT and BHMT-2, their full-length cDNAs were cloned and sequenced, and their corresponding genes were characterized. The genes are adjacent to each other on the same chromosome, and to study the evolutionary relationship between them, all the available sequences from 37 species of deuterostomes were analyzed. Unlike BHMT, the BHMT-2 gene is not found in sea urchins, amphibians, reptiles and birds, indicating it was derived from BHMT following a gene duplication event in mammals. These findings imply that the BHMT-2 gene may offer an advantage to mammals in scavenging Met from the environment. As…
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