Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
What RNA World ?? Ancestral polypeptides likely participated in the origins of translation
A widespread consensus holds that protein synthesis according to a genetic code was launched entirely by sophisticated RNA molecules that played both coding and functional roles. This belief persists, unsupported by phylogenetic evidence for ancestral ribozymes that catalyzed either amino acid activation or tRNA aminoacylation. By contrast, we have adduced strong experimental evidence that the most highly conserved portions of contemporary aminoacyl-tRNA synthetases, aaRS accelerate both reactions well in excess of rates achieved by RNA aptomers derived from combinatorial libraries and of rates required for primordial protein synthesis. Such ancestral enzymes, or “Urzymes”, characterized for Class I (TrpRS (Pham et al, 2010, 2007) and LeuRS (Collier et al. 2013); 130 residues) and Class II (HisRS; 120-140 residues; (Li et al. 2011)) synthetases generally have promiscuous amino acid specificities, whereas ATP and cognate tRNA affinities are within an order of magnitude of those for contemporary enzymes. These characteristics match or exceed expectations for the primordial catalysts necessary to launch protein synthesis. Structural hierarchies in Class I and II aaRS also exhibit plateaus of increasing enzymatic activity, suggesting that catalysis by peptides similar to the Aleph motif identified by Trifonov (Sobolevsky et al.) may have been both necessary and sufficient to launch protein synthesis. Sense/antisense alignments of TrpRS and HisRS Urzyme coding sequences reveal unexpectedly high middle-base complementarity that increases in reconstructed ancestral nodes (Chandrasekaran et al.), consistent with the proposal of Rodin and Ohno (Rodin & Ohno, 1995). Thus, these ancestors were likely coded by opposite strands of the same gene, favoring simultaneous expression of aaRS activating both hydrophobic (core) and hydrophilic (surface) amino acids. Our results support the view that aaRS co-evolved with cognate tRNAs from a much earlier stage than that envisioned under the RNA World hypothesis, and that their descendants make up appreciable portions of the proteome.
This research has been supported by NIGMS 78227.
Pham Y, et al. (2007) A Minimal TrpRS Catalytic Domain Supports Sense/Antisense Ancestry of Class I and II Aminoacyl-tRNA Synthetases. Mol. Cell 25:851-862.
Collier ML, Ibba M, & Carter CW, Jr (2013) LeuRS Urzyme: a Second Class I Aminoacyl-tRNA Synthetase Urzyme. Journal of Biologial Chemistry In Preparation.
Li L, Weinreb V, Francklyn C, & Carter CW, Jr (2011) Histidyl-tRNA Synthetase Urzymes: Class I and II Aminoacyl-tRNA Synthetase Urzymes have Comparable Catalytic Activities fo Cognate Amino Acid Activation. Journal Biological Chemistry 286:10387-10395.
Sobolevsky Y, Frenkel ZM, & Trifonov EN (2007) Combinations of Ancestral Modules in Proteins. J. Mol. Evol. 65:640-650.
Chandrasekaran SN, Yardimci GG, Erdogan O, & Carter CW, Jr (2013) Statistical Evaluation of the Rodin-Ohno Hypothesis: Sense/Antisense Coding of Ancestral Class I and II Aminoacyl-tRNA Synthetases. Mol. Biol. Evol. Under revision.
Rodin SN & Ohno S (1995) Two Types of Aminoacyl-tRNA Synthetases Could be Originally Encoded by Complementary Strands of the Same Nucleic Acid. Orig. Life Evol. Biosph. 25:565-589.
Charles W. Carter, Jr
Biochemistry and Biophysics