Origin of genetic code: A needle in the haystack of tRNA sequences

摘要

Because the amino acid-trinucleotide algorithm of the genetic code is established by the specific aminoacylations of tRNAs, the sequences and structure of tRNAs have long been investigated with the idea of learning about the possible origin of the code. The idea is that elements of the code might appear in parts of the tRNA structure other than the anticodon. These parts might represent primordial components of the tRNA molecule, which possibly served as structures associated with the aminoacylations of particular amino acids. The paper by Rodin et al. in the current issue of the Proceedings points out a previously unrecognized relationship between tRNA sequences that could, be relevant to the origin of the code. Investigations of this sort are inherently difficult. On the one hand, more than 2000 tRNA sequences have been collectively determined for specific eubacterial, archaebacterial, and lower and higher eukaryote organisms. This large data base of sequences provides ample material for analyses which attempt to find vestiges of the genetic code in parts of the tRNA structure outside of the anticodon. On the other hand, with only four nucleotides, the random chance of a specific sequence relationship is far higher with tRNAs than with proteins made up of 20 amino acids. The possibilities for random "hits" increase considerably the background "noise" that must be discounted. The other, related problem is that tRNAs are ancient molecules, probably arising more than one billion years ago with the earliest life forms. Consequently, they have undergone many mutational variations and changes in evolution. With only four nucleotides and a long evolutionary history, searching for vestiges of the genetic code within the tRNA structure is like searching for a small needle in a big haystack.