Selective charging of tRNA isoacceptors explains patterns of codon usage

Abstract

We modeled how the charged levels of different transfer RNAs (tRNAs) that carry the same amino acid (isoacceptors) respond when this amino acid becomes growth-limiting. The charged levels will approach zero for some isoacceptors (such as tRNA2Leu) and remain high for others (such as tRNA4Leu), as determined by the concentrations of isoacceptors and how often their codons occur in protein synthesis. The theory accounts for (synonymous) codons for the same amino acid that are used in ribosome-mediated transcriptional attenuation, the choices of synonymous codons in trans-translating transfermessenger RNA, and the overrepresentation of rare codons in messenger RNAs for amino acid biosynthetic enzymes.