The Ancient Operational Code is Embedded in the Amino Acid Substitution Matrix and aaRS Phylogenies

Abstract

The underlying structure of the canonical amino acid substitution matrix (aaSM) is examined by considering stepwise improvements in the differential recognition of amino acids according to their chemical properties during the branching history of the two aminoacyl-tRNA synthetase (aaRS) superfamilies. The evolutionary expansion of the genetic code is described by a simple parameterization of the aaSM, in which (i) the number of distinguishable amino acid types, (ii) the matrix dimension, and (iii) the number of parameters, each increases by one for each bifurcation in an aaRS phylogeny. Parameterized matrices corresponding to trees in which the size of an amino acid sidechain is the only discernible property behind its categorization as a substrate, exclusively for a Class I or II aaRS, provide a significantly better fit to empirically determined aaSM than trees with random bifurcation patterns. A second split between polar and nonpolar amino acids in each Class effects a vastly greater further improvement. The earliest Class-separated epochs in the phylogenies of the aaRS reflect these enzymes' capability to distinguish tRNAs through the recognition of acceptor stem identity elements via the minor (Class I) and major (Class II) helical grooves, which is how the ancient Operational Code functioned. The advent of tRNA recognition using the anticodon loop supports the evolution of the optimal map of amino acid chemistry found in

High-Resolution, Multidimensional Phylogenetic Metrics Identify Class I Aminoacyl-tRNA Synthetase Evolutionary Mosaicity and Inter-modular ‘Coupling

“…Descent of Class I and II aaRS from a single bidirectional ancestral gene [10, 14, 18, 19, 21, 32, 33] would underscore the likelihood that the aaRS of both families diverged, rather than converging to similar functions from different sources. Thus, the genetic coding table itself likely evolved by bifurcating pre-existing aaRS genes into specialized enzymes whose more discriminating specificities for tRNA and amino acid substrates enabled daughter synthetases to differentiate groups amino acids that previously had functioned as synonymous [46, 48, 58, 59]. It would be surprising if other branches of the proteome had not diverged from the ancestral aaRS, as suggested in Fig 6.…”

“…Amino acid chemistry underlies the metric form of amino acid substitution matrices (aaSM) generally required for the logically circular process of creating an amino acid sequence alignment by optimizing the constraints of some aaSM and then building a phylogenetic tree from the alignment according to those constraints [8].…”

“…That operation was repeated for trees built for the full scaffold MSA, (Full), the Urzyme, CP1, protozyme (segment A in Fig 1), and seven subset MSAs each consisting of twenty amino acids in blocks of five residues as described in Methods. For the eleven rows of the design matrix (Table 2), we computed S for populations of trees constructed using the conventional WAG [39] substitution matrix and repeated using the more recent LG [40] substitution matrix used in [8].…”

“…Phylogenetic analyses of the Class I aaRS superfamily [2][3][4][5][6][7][8] generally agree that clades for each amino acid are monophyletic, divide into three subclasses [1,9], including IleRS, ValRS, LeuRS, and MetRS (Subclass IA); GluRS and GlnRS (Subclass IB); and TyrRS and TrpRS (Subclass IC). Restricting analysis to the bacterial aaRS as they point more faithfully to the root of protein synthesis [10], we exclude the archaeal Subclass IB Class I LysRS.…”

Reciprocally-Coupled Gating: Strange Loops in Bioenergetics, Genetics, and Catalysis

“…We have argued that the choice of pathways for the expansion of the coding table was not arbitrary, but formally resembled the shifting gears of a bicycle derailleur [11]. The succession of nodes in aaRS superfamily growth during expansion of the coding table from 2 to 20 amino acids is now potentially accessible by phylogenetic methods [99,117] and will supplement existing models for code development [116,118], perhaps in unexpected ways.…”