Prebiotic methylation and the evolution of methyl transfer reactions in living cells

An hypothesis is presented for the prebiotic origin of methyl groups and th e evolution of methyl transfer reactions in living cells. This hypothesis, described in terms of prebiotic and early biotic chemical evolution, is bas ed on experimental observations in our lab and in those of others, and on t he mechanisms of enzymatic methyl transfer reactions that occur in living c ells. Of particular interest is our demonstration of the reductive methylat ion of ethanolamine and glycine in aqueous solution by excess formaldehyde. These reactions, involving prebiotic compounds and conditions, are mechani stically analogous to the de novo origin of methyl groups in modern cells b y reduction of methylene tetrahydrofolate. Furthermore, modern cellular met hyl transfers from S-adenosylmethionine to amine nitrogen may involve forma ldehyde as an intermediate and subsequent reductive methylation, analogous to the prebiotic chemistry observed herein.