We have invited a number of distinguished microbiologists to share some of their thoughts with us.
Although the genetic code is well established, a very exciting unsolved problem is discovering how codons were related to amino acids in the evolution of protein synthesis. How did a tRNA and a tRNA synthetase first evolve, and what was their ancestral source? How were the genes for the first tRNA and tRNA synthetase duplicated and how was their specificity varied? Can we offer any explanation for why there are two classes of tRNA synthetases? Can one predict which tRNAs evolved from one another? Similarly, can we predict which tRNA synthetases evolved from an existing tRNA synthetase?
A related series of exciting experiments would be to attempt to reproduce some evolutionary events and determine how many mutational changes it would take – and where – to evolve a tRNA synthetase with new specificity from an existing synthetase. Suppression studies many years ago showed that tRNAs may acquire new decoding specificity following single mutational changes, but synthetase suppressors were not recovered, as I recall. Also, we now know that synthetases recognize both the anticodon and acceptor end sequence of each tRNA – is this consistent with what is known about suppressing tRNAs?
Carter CW Jr. (2008). Whence the genetic code? Thawing the 'Frozen Accident'. Heredity 100, 339–340
Charles Yanofsky is Professor Emeritus of Biological Sciences at Stanford University and a 2003 recipient of the National Medal of Science.