The Evolution of Alternative Genetic Codes

Abstract

The genetic code is so critical to the production of all proteins in the cell that it was once thought to be a “frozen accident”, incapable of evolving further. However, the discovery of alternative genetic codes in dozens of clades of bacteria, eukaryotes, archaea, organelles, and viruses has shown that it is flexible to some degree. In Chapter 1, I review major concepts in alternative genetic code evolution: the evolutionary trajectories by which alternative genetic codes can evolve, how changes to the translational machinery allow for codon reassignment, and potential selective pressures that could drive reassignment. In Chapters 2 and 3, I describe Codetta, a computational tool for predicting the genetic code from a nucleotide sequence. In Chapter 2, I use Codetta to screen over 250,000 bacterial and archaeal genomes and identify five bacterial clades using new genetic codes. All of the new reassignments affect arginine codons, highlighting a potential sensitivity of arginine codons to reassignment. In a clade of uncultivated Enterosoma bacteria, AGG has been reassigned from arginine to become the dominant methionine codon and appears to have evolved by a change in the aminoacylation of the original arginine tRNA. The other reassignments all affect the arginine codons CGA and/or CGG. These clades all have very low genomic GC content, an evolutionary force which likely drove GC-rich codons to rarity and allowed for their reassignment. The CGA and CGG reassignments are explored in more detail in Chapter 4, including close outgroup species with unusual tRNA features that may shed light on intermediate stages of reassignment.