MOLECULAR PHYLOGENETICS OF A PROTEIN REPAIR METHYLTRANSFERASE

Protein-L-isoaspartyl (D-aspartyl) O-methyltransferase (E.C. 2.1.1.71) is a well-conserved and widely distributed protein repair enzyme that methylates isomerized or racemized aspartyl residues in age-damaged p roteins. We exploited the availability of protein sequences from 10 di verse animal, plant and bacterial taxa to construct a phylogenetic tre e and determine the rates of amino acid substitution for this enzyme. We used a likelihood ratio rest to show that this enzyme fulfills the conditions for a molecular crock. We found that the rate of substituti on is 0.39 amino, acid substitutions per site per 10(9) years and rema ins relatively constant from bacteria to humans. We argue that this de gree of sequence conservation may result from the functional con strai nts necessitated by the requirement to specifically recognize altered aspartyl but nor normal aspartyl residues in proteins. Relative rate a nalysis of the Caenorhabditis elegans sequence suggests that the amino acid substitution rate in the nematode lineage may be higher than tha t in other lineages and that the divergence of nematodes may have been a more recent event than suggested by previous analysis. (C) 1997 Els evier Science Inc.