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

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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 the later genetic code, an essentially digital categorization, in which polarity is the major functional property, compensating for the unrefined, haphazard differentiation of amino acids achieved by the operational code.

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Notes

  1. We use“differentiable” rather than “distinguishable” when we want to emphasise the means of making a distinction, rather than simply the existence of a distinction, especially among amino acids.

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Acknowledgements

PRW thanks the Alexander von Humboldt Foundation for its continual support; both Peter Stadler and Alexei Drummond for their encouragement, more than a decade ago, to carry out this study; Andrew Torda for advice about substitution matrices and Charlie Carter for constant helpful correspondence and discussions.

Funding

This research was supported by Australian Research Council (ARC) Discovery Grant DP150100088 to Barbara R. Holland and Jeremy G. Sumner, and Research Training Program scholarship to Julia A. Shore.

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Authors and Affiliations

  1. School of Natural Sciences, University of Tasmania, Churchill Avenue, Tasmania, 7005, Australia

    Julia A. Shore, Barbara R. Holland & Jeremy G. Sumner

  2. Integrative Transcriptomics, Interfaculty Institute for Biomedical Informatics, University of Tübingen, Sand 14, 72076, Tübingen, Germany

    Kay Nieselt

  3. Department of Physics and Te Ao Marama Centre for Fundamental Inquiry, University of Auckland, PB 92109, Auckland, 1142, Aotearoa, New Zealand

    Peter R. Wills

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  1. Julia A. Shore
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Correspondence to Julia A. Shore.

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Shore, J.A., Holland, B.R., Sumner, J.G. et al. The Ancient Operational Code is Embedded in the Amino Acid Substitution Matrix and aaRS Phylogenies. J Mol Evol 88, 136–150 (2020). https://doi.org/10.1007/s00239-019-09918-z

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