Energy mapping of the genetic code and genomic domains: implications for code evolution and molecular Darwinism.

Horst H Klump,Kenneth J Breslauer,Jens Völker

doi:10.1017/s0033583520000098

Horst H Klump, Kenneth J Breslauer + Show 1 more

Open Access

https://doi.org/10.1017/s0033583520000098

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Abstract

When the iconic DNA genetic code is expressed in terms of energy differentials, one observes that information embedded in chemical sequences, including some biological outcomes, correlate with distinctive free energy profiles. Specifically, we find correlations between codon usage and codon free energy, suggestive of a thermodynamic selection for codon usage. We also find correlations between what are considered ancient amino acids and high codon free energy values. Such correlations may be reflective of the sequence-based genetic code fundamentally mapping as an energy code. In such a perspective, one can envision the genetic code as composed of interlocking thermodynamic cycles that allow codons to 'evolve' from each other through a series of sequential transitions and transversions, which are influenced by an energy landscape modulated by both thermodynamic and kinetic factors. As such, early evolution of the genetic code may have been driven, in part, by differential energetics, as opposed exclusively by the functionality of any gene product. In such a scenario, evolutionary pressures can, in part, derive from the optimization of biophysical properties (e.g. relative stabilities and relative rates), in addition to the classic perspective of being driven by a phenotypical adaptive advantage (natural selection). Such differential energy mapping of the genetic code, as well as larger genomic domains, may reflect an energetically resolved and evolved genomic landscape, consistent with a type of differential, energy-driven 'molecular Darwinism'. It should not be surprising that evolution of the code was influenced by differential energetics, as thermodynamics is the most general and universal branch of science that operates over all time and length scales.

Highlights

Evolution of the code, including error minimization (Freeland et al, 2003; Novozhilov and Koonin, 2009), stereochemical (Yarus et al, 2005; Polyansky and Zagrovic, 2013; de Ruiter and Zagrovic, 2015), and coevolution theories (Di Giulio, 2004; Wong, 2005)
Once organisms started using such codes to connect replication to translation, they evolved more rapidly toward a thermodynamically driven code. We prefer the former perspective of an early stage, energy-driven, nonrandom evolutionary shaping of the genetic code through a series of mutations within stable, prebiotic ‘codon duplexes’, all controlled via families of interlocking energy cycles
One might speculate, that the degeneracy associated with the use of multiple codons of differential stabilities to code for the same amino acid reflects a form of thermodynamic selection; one in which codon energetics is more determinatory of usage frequency than a codon’s chemical syntax alone

Summary

Biophysical origins and evolution of the genetic code

Within the context of an energy-based perspective for the origin and evolution of the genetic code, one can hypothesize that the original ancestral codons were comprised of a family of ‘prebiotic’ duplexes of sufficient stability to avoid dissociation from their antiparallel, complementary codons. One might reasonably envision that such codon couplets would code for the most ancient amino acids (Miller, 1953; Miller and Urey, 1959; Miller et al, 1976; Trifonov and Bettecken, 1997; Trifonov, 2000, 2004) if given the proper translational machinery This core of ‘prebiotic’ ‘codon duplexes’ could have produced the rest of the code through a sequential series of transition and transversion mutations, the order of which is controlled/regulated/influenced via families of interlocking energy cycles. Evolution may result from a mixture of contributions from classic, natural selection, Darwinian theory, as well as from what can be called ‘molecular Darwinism’ (Eigen, 1976), or ‘Watson–Crick Darwinism’ In the latter context, some phenotypical characteristics might persist since they are coded for by more stable domains in the genome, even if such characteristics do not maximize species survival. Perhaps early evolution of the genetic code can be viewed in terms of the differential stabilities of codon/complementary codon couplets that form antiparallel trimeric duplexes, as opposed to exclusively in terms of the functionality of any gene product

The genetic code as an energy code

Correlating trimeric duplex stability with amino acid coding properties

Concluding remarks

Going forward