Protein Folding as a Transition Step from Ancient to the Modern Life Forms

Abstract

Several lines of evidence suggest that the first proteins on earth likely contained significantly fewer than the modern 20 amino acids. Subsequently many researchers examined the evolution of the genetic code using different criteria. Trifonov combined 40 different of these single-factor criteria into a consensus and proposed the following temporal order of addition for the amino acids: G/A, V/D, P, S, E/L, T, R, N, K, Q, I, C, H, F, M, Y, W. Brooks and co-workers estimated the amino acid composition for the Last Universal Ancestor (LUA). This composition was depleted and enriched in several of Trifonov's modern and ancient amino acids, respectively. The Brooks and coworker set of ancient proteins contains two almost equal-sized subsets: RNA-associated proteins and enzymes. We found the RNA-associated proteins from the LUA to be much more extensively depleted in the modern amino acids than were the enzymes. We also noticed that the more ancient amino acids are predominantly disorder-promoting while the more modern amino acids are predominantly order-promoting. Two different disordered protein predictors suggest the RNA-associated proteins to be disordered and the enzymes to be structured, which agrees with laboratory experiments on the modern protein counterparts. If the RNA-associated proteins are representative of the proteins present in the earliest life forms, then these proteins lacked regular 3D structure. Therefore, we propose that: 1. the change from ancient to modern life forms depended on the evolution a protein disorder-to-structure transition, thus enabling the formation of protein enzymes; and 2. this evolutionary disorder-to-order transition was enabled by the introduction of the structure-promoting amino acids during the modernization of the genetic code.