Diversification of aminoacyl-tRNA synthetase activities via genomic duplication

Abstract

Intricate evolutionary events enabled the emergence of the full set of aminoacyl-tRNA synthetase (aaRS) families that define the genetic code. The diversification of aaRSs has continued in organisms from all domains of life, yielding aaRSs with unique characteristics as well as aaRS-like proteins with innovative functions outside translation. Recent bioinformatic analyses have revealed the extensive occurrence and phylogenetic diversity of aaRS gene duplication involving every synthetase family. However, only a fraction of these duplicated genes has been characterized, leaving many with biological functions yet to be discovered. Here we discuss how genomic duplication is associated with the occurrence of novel aaRSs and aaRS-like proteins that provide adaptive advantages to their hosts. We illustrate the variety of activities that have evolved from the primordial aaRS catalytic sites. This precedent underscores the need to investigate currently unexplored aaRS genomic duplications as they may hold a key to the discovery of exciting biological processes, new drug targets, important bioactive molecules, and tools for synthetic biology applications.

Symmetrical distributions of aminoacyl-tRNA synthetases during the evolution of the genetic code

“…The symmetry groups found in the RNA codes pinpoint to intricacies in the evolution of aaRSs in conjunction with the evolution of the genetic code itself. The biological usefulness of the results emphasizes the roles of extensive occurrence of aaRS gene duplication involving every synthetase family, Horizontal Gene Transfer (including concessions, swapping of genes, recombination events), and a Lamarckian mode of inheritance for the diversification and innovation of synthetases (Vetsigian et al 2006 ; Krahn et al 2022 ; Rubio et al 2015 ).…”

HetMM: A Michaelis-Menten model for non-homogeneous enzyme mixtures

“…Many genomes express isozymes; enzymes with distinct sequences, but common ancestry and common catalytic activity, such as the multiple aminoacyl-tRNA synthetase gene duplicates that coexist in bacterial cells. 8 In some cases, purified enzyme preparations contain multiple isozymes, such as cytochrome oxidase. 7 , 9 But even a single gene can give rise to a heterogeneous mixture of protein products, through transcriptional or translational errors, alternative initiation or splicing, or post-translational modification, among other processes.…”

HetMM: A Michaelis-Menten model for non-homogeneous enzyme mixtures

“…Indeed, there are numerous cases of non-homogeneous biocatalytic systems, both in vitro and in vivo . Many genomes express isozymes; enzymes with distinct sequences, but common ancestry and common catalytic activity, such as the multiple aminoacyl-tRNA synthetase gene duplicates that coexist in bacterial cells [7]. In some cases, purified enzyme preparations contain multiple isozymes, such as cytochrome oxidase [6], [8].…”