Seminars & Colloquia Calendar

 Abstract:  Frequencies of synonymous codons (nucleotide triplets in the gene which are translated into amino acids by the ribosome) are typically non-uniform, despite the fact that such codons correspond to the same amino acid in the genetic code. This phenomenon, known as codon bias, is broadly believed to be due to a combination of factors including genetic drift, mutational effects, and selection for speed and accuracy of codon translation; however, quantitative modeling of codon bias has been elusive. I will present a biophysical model which explains genome-wide codon frequencies observed across 20 organisms. Our model implements detailed codon-level treatment of mutations, and includes two contributions to codon fitness which describe codon translation speed and accuracy. We find that the observed patterns of genome-wide codon usage are consistent with a strong selective penalty for mistranslated amino acids, while the dependence of codon fitness on translation speed is much weaker on average. Treating the translation process explicitly in the context of a finite ribosomal pool has allowed us to estimate mutation rates directly from the gene sequences. Reminiscent of Drake's observation that mutation rates are inversely correlated with the genome size, we predict that mutation rates are inversely proportional to the number of genes. Overall, our approach offers a unified biophysical and population genetics framework for understanding codon bias.