Match fitness landscapes for macromolecular interaction networks: Selection for translational accuracy and rate can displace tRNA-binding interfaces of non-cognate aminoacyl-tRNA synthetases

Abstract

Advances in structural biology of aminoacyl-tRNA synthetases (aaRSs) have revealed incredible diversity in how aaRSs bind their tRNA substrates. The causes of this diversity remain mysterious. We developed a new class of highly rugged fitness landscape models called match landscapes, through which genes encode the assortative interactions of their gene products through the complementarity and identifiability of their structural features. We used results from coding theory to prove bounds and equalities on fitness in match landscapes assuming additive interaction energies, macroscopic aminoacylation kinetics including proofreading, site-specific modifiers of interaction, and selection for translational accuracy in multiple, perfectly encoded site-types. Using genotypes based on extended Hamming codes we show that over a wide array of interface sizes and numbers of encoded cognate pairs, selection for translational accuracy alone is insufficient to displace the tRNA-binding interfaces of aaRSs. Yet, under combined selection for translational accuracy and rate, site-specific modifiers are selected to adaptively displace the tRNA-binding interfaces of non-cognate aaRS–tRNA pairs. We describe a remarkable correspondence between the lengths of perfect RNA (quaternary) codes and the modal sizes of small non-coding RNA families.