Alternative genetic code for amino acids and transfer RNA revisited

The genetic code is highly conserved among all organisms and its evolution is thought to be strictly limited. However, an increasing number of studies have reported non-standard codes in prokaryotic and eukaryotic genomes. Most of these deviations from the standard code are attributable to tRNA changes relating to, for example, codon/anticodon base pairing and tRNA/aminoacyl-tRNA synthetase recognition. In this review, we focus on tRNA, a key molecule in the translation of the genetic code, and summarize the most recently published information on the evolutionary divergence of the tRNAs. Surprisingly, although higher eukaryotes, such as the nematode (worm), utilize the standard genetic code, newly identified nematode-specific tRNAs (nev-tRNAs) translate nucleotides in a manner that transgresses the code. Furthermore, a variety of additional functions of tRNAs, beyond their translation of the genetic code, have emerged rapidly. We also review these intriguing new aspects of tRNA, which have potential impacts on translational control, RNA silencing, antibiotic resistance, RNA biosynthesis, and transcriptional regulation.