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Project Progress

The focus of our work is reconstruction of our evolutionary beginnings by characterizing the very earliest ancestral proteins that existed even before the theoretical Last Common Ancestor cell. By analyzing the sequences of extant proteins and grouping them by commonalities, we should be able to reconstruct the numbers and types of earliest ancestor molecules of life on earth.

We have identified a very large family of weakly similar proteins that could have arisen from a single ancestor that generated four types of enzymes: dehydrogenases, epimerases, isomerases and dehydratases. Using both PSI-BLAST and DARWIN sequence analysis protocols to examine similarities among dehydrogenases of the model organism E. coli, a set of proteins was identified, the same set by both methods, that contains not only a number of NAD-requiring dehydrogenases but also some NAD-requiring epimerases, dehydratases and isomerases as well. The latter three reaction types do not involve oxidation/reduction, yet these enzymes require the NAD cofactor. Use of NAD in non-redox reactions is unusual and may have been a very early step in evolution to generate from dehydrogenases a variety of types of enzymes. A tree of the set of proteins from E. coli has two clear groups, one containing only the NAD-requiring dehydrogenases, the other containing the NAD-requiring epimerases, dehydratases and isomerases, consistent with generation from dehydrogenases of a set of enzymes capable of quite different reactions.

Many other examples of divergence of function from a common sequence are also present in E. coli. We did a survey of similarity and function of proteins within E. coli and collected 15 examples of pairs or groups of 3 or 4 of enzymes whose sequences were clearly related, but the reactions they catalyze are different. We plan to investigate each case with the view of proposing characteristics of some of the most ancient proteins and their divergent progeny.