Genetic Code Optimization for Cotranslational Protein Folding: Codon Directional Asymmetry Correlates with Antiparallel Betasheets, tRNA Synthetase Classes

Abstract

A new codon property, codon directional asymmetry in nucleotide content (CDA), reveals a biologically meaningful genetic code dimension: palindromic codons (first and last nucleotides identical, codon structure XZX) are symmetric (CDA = 0), codons with structures ZXX/XXZ are 5'/3' asymmetric (CDA = - 1/1; CDA = - 0.5/0.5 if Z and X are both purines or both pyrimidines, assigning negative/positive (-/+) signs is an arbitrary convention). Negative/positive CDAs associate with (a) Fujimoto's tetrahedral codon stereo-table; (b) tRNA synthetase class I/II (aminoacylate the 2'/3' hydroxyl group of the tRNA's last ribose, respectively); and (c) high/low antiparallel (not parallel) betasheet conformation parameters. Preliminary results suggest CDA-whole organism associations (body temperature, developmental stability, lifespan). Presumably, CDA impacts spatial kinetics of codon-anticodon interactions, affecting cotranslational protein folding. Some synonymous codons have opposite CDA sign (alanine, leucine, serine, and valine), putatively explaining how synonymous mutations sometimes affect protein function. Correlations between CDA and tRNA synthetase classes are weaker than between CDA and antiparallel betasheet conformation parameters. This effect is stronger for mitochondrial genetic codes, and potentially drives mitochondrial codon-amino acid reassignments. CDA reveals information ruling nucleotide-protein relations embedded in reversed (not reverse-complement) sequences (5'-ZXX-3'/5'-XXZ-3').

Keywords: Alpha helix; Beta turn; Codon-amino acid assignment; Mitochondrial genetic code; Secondary structure; Synonymous codon.

Graphical abstract

Fig. 1

Fujimoto's tetrahedral codon stereo-table, a genetic code's representation that seems non-random in relation to codon directional asymmetry. The tetrahedron has four equal, equilateral faces (A–D), and consist each of 16 equilateral triangles representing each one codon. Red circles: CDA < 0; blue squares: CDA > 0. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Antiparallel betasheet conformation parameter of amino acids as a function of the mean codon directional asymmetry (CDA) of codons assigned to that amino acid, for the standard genetic code. Amino acids aminoacylated by tRNA synthetases from class I have open circles, filled circles are for tRNA synthetases from class II.

Fig. 3

Correlation between antiparallel betasheet conformation parameter of amino acids and mean directional asymmetry (CDA) of codons assigned to that amino acid as a function of the correlation between CDA and the tRNA synthetase class for the corresponding amino acid for different genetic codes. Correlations are Pearson correlation coefficients. Filled/open circles are nuclear/mitochondrial genetic codes, shaded circles are for genetic codes existing in nuclei and mitochondria. The line indicates y = x. Nuclear genetic codes tend to optimise the association between CDA and tRNA synthetase classes, mitochondrial genetic codes tend to optimise the association between CDA and the antiparallel betasheet conformation parameter. Most mitogenome-encoded proteins are transmembrane proteins, hence antiparallel betasheets are particularly frequent in these proteins. Hence genetic code evolution optimises the CDA-antiparallel betasheet association in mitochondria. Open circles: mitochondrial genetic codes; filled circles: nuclear genetic codes; shaded circles: genetic codes used in nuclei and mitochondria.

Fig. 4

Lepidosaurian body temperature as a function of mean codon directional asymmetry of codons in protein coding genes encoded by complete mitogenomes available in GenBank. Compilation of body temperatures and mitochondrial genomes as in Table 1 of Seligmann and Labra . Agamidae are indicated by triangles, Gekkota by crosses and Lacertidae by filled circles. Species from various other families have open circles.

Fig. 5

Developmental stability of bilateral counts of subdigital lamellae on 4th toe of Lepidosauria (estimated by Pearson correlation coefficients r between counts on left and right sides) as a function of mean codon directional asymmetry (CDA) of codons in all 13 genes of mitogenome-encoded transmembrane proteins.