Abstract

Zoom link: https://maths-cam-ac-uk.zoom.us/j/94018037756

All living cells synthesize proteins by transcribing the hereditary information in their DNA into strands of messenger RNA which are subsequently translated into amino acid sequences. The genetic code that assigns triplets of nucleotides (codons) to their corresponding amino acids is redundant, since most amino acids are encoded by several codons. Mutations that change the DNA sequence but leave the amino acid sequence unchanged are called synonymous. Motivated by recent experiments on an antibiotic resistance gene, in this work we investigate genetic interactions between synonymous mutations in the framework of exclusion models of translation. We show that the range of possible interactions is markedly different depending on whether translation efficiency is assumed to be proportional to ribosome current or ribosome speed. Based on a rigorous proof of a monotonicity property of the particle current in the inhomogeneous totally asymmetric simple exclusion process, we argue that mutational effects on the ribosome current have a definite sign that is independent of genetic background. In contrast, the effect-sign on ribosome speed can vary depending on the presence of other mutations, a result that is demonstrated using configurations of multiple translational bottlenecks induced by slow codons.