The fitness landscapes of translation

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.

The fitness landscapes of translation

“…For certain conditions they observed that the stationary current was increasing with increasing f , or decreasing with increasing p 1 . We have repeated these simulations and find the expected monotonic behavior throughout [17]. The results reported in [39] may have been caused by insufficient relaxation to the stationary state 1 .…”

“…If efficiency is identified with the stationary ribosome current, we prove rigorously that sign epistasis is not possible. In contrast, if efficiency is taken to be the average speed of a ribosome (equivalently, the inverse of the ribosome travel time), then plausible scenarios giving rise to sign-epistatic interactions are readily found, and fitness landscapes that are qualitatively similar to those observed experimentally in [7] can be constructed [17]. We conclude, therefore, that there are (at least) two different fitness landscapes of translation, one of which is always simple, whereas the other displays a complex structure of hierarchically organized neutral networks.…”