MAXIMIZING TRANSCRIPTION EFFICIENCY CAUSES CODON USAGE BIAS

The rate of protein synthesis depends on both the rate of initiation o f translation and the rate of elongation of the peptide chain. The rat e of initiation depends on the encountering rate between ribosomes and mRNA; this rate in turn depends on the concentration of ribosomes and mRNA. Thus, patterns of codon usage that increase transcriptional eff iciency should increase mRNA concentration, which in turn would increa se the initiation rate and the rate of protein synthesis. An optimalit y model of the transcriptional process is presented with the predictio n that the most frequently used ribonucleotide at the third codon site s in mRNA molecules should be the same as the most abundant ribonucleo tide in the cellular matrix where mRNA is transcribed. This prediction is supported by four kinds of evidence. First, A-ending codons are th e most frequently used synonymous codons in mitochondria, where ATP is much more abundant than that of the three other ribonucleotides. Seco nd, A-ending codons are more frequently used in mitochondrial genes th an in nuclear genes. Third, protein genes from organisms with a high m etabolic rate use more A-ending codons and have higher A content in th eir introns than those from organisms with a low metabolic rate.