The Evolution of Functional Proteins

How did enzyme catalysts evolve? First, a single catalytic group of rudimentary effectiveness could have been incorporated into a single short peptide. In the second stage, several peptides would bind together, providing a multichain assembly with improved catalytic effectiveness. These peptides would eventually be joined together in a single chain to increase thermal stability and ensure the linked inheritance of all the elements of the complex. Finally, this rough protein would be refined and improved by classical selection processes. Evidence for the second step comes from investigation of the cDNA sequence and the genomic sequence of a gene from Tetrahymena and forms the basis of the exon microgene theory (1). This hypothesis suggests that in the early stages of the evolution of functional proteins RNA consisted of exon microgenes, each of which terminated in an amber codon (UAG) and encoded independently translated peptides. These peptides would form catalytic, multichain assemblies that were the rudimentary precursors of the enzymes we know today. In support of these ideas, complementation studies have shown that a protein "refragmented" at its exon-exon boundaries produces a functional multichain protein complex. These studies have been expanded to a more general investigation of the resilience of protein catalytic function in the face of insults to protein structural integrity.