The fitness landscapes of translation

TL;DR

This paper explores how different models of translation efficiency influence genetic interactions between synonymous mutations, revealing that the nature of these interactions varies significantly depending on the underlying assumptions about ribosome dynamics.

Contribution

It introduces a comparative analysis of translation models showing how assumptions about ribosome current versus speed affect genetic interaction predictions.

Findings

Interaction effects depend on translation efficiency assumptions.

Sign effects are background-independent in current-based models.

Sign effects vary with mutations in bottleneck configurations.

Abstract

Motivated by recent experiments on an antibiotic resistance gene, 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. In the first case every mutational effect has a definite sign that is independent of genetic background, whereas in the second case the effect-sign can vary depending on the presence of other mutations. The latter result is demonstrated using configurations of multiple translational bottlenecks induced by slow codons.