Mapping the DNA genetic code using energy flow

Scientists are proposing a new perspective on the origin of the genetic code from the standpoint of thermodynamics (energy flow).

Writing in the Quarterly Reviews of Biophysics, published Nov. 4, the researchers note that the modern view of Darwinian evolution is that a species preserves those attributes that give it "a survival advantage in a given environment." This is the modern interpretation of Darwinian "natural selection" or "survival of the fittest." The scientists are from Rutgers University in New Jersey and the University of Cape Town in South Africa.

Traditionally, this explanation is said to account for the unique nature of the genetic code found in living organisms. There are 10⁸⁴ different possibilities for a genetic code, based on the four types of DNA bases: adenine (A), thymine (T), guanine (G) and cytosine (C), and how they combine and intertwine in a helical form.

Any three of the base pairs in a particular sequence forms a codon. Each codon produces one of 20 possible amino acids that form the proteins and other structures in the human body. From the astronomical number of possible geometric arrangements, only one genetic code emerges.

But this is only part of the evolution equation, the researchers write. They prefer the perspective "of an early stage, energy-driven, non-random evolutionary shaping of the genetic code." This occurs, in their view, "through a series of mutations within particularly stable, prebiotic ‘codon duplexes,’ all controlled via families of interlocking energy cycles."

Thermodynamics, the authors argue, provides a way to map the genetic code into an "energy code." By examining the energy signatures of different DNA regions, they construct a geometric map that correlates the frequency with which a given codon is used for a particular amino acid and the resulting free energy.

Instead of looking at the correlation from the point of view of chemistry, the authors propose a thermodynamic analysis: that "codon energetics is more determinatory of usage frequency than a codon's chemical syntax alone."

To illustrate the thermodynamic cycles, they arrange the 64 different possible combinations of codons by frequency of usage for selected amino acids into a geometry of eight cubes. Then they put the cubes into a scaffolding at the corners of a four-dimensional cube known as a hypercube. In this way, they model the energy flow of DNA sequence alterations.

Differences in energy flow, they propose, may influence an organism's physical structure and enable specific biological functions.

They propose that the coupled energy cycles they modeled "controlled the transition and transversion mutations of a group of the 24 most ancient (prebiotic) and stable codon pairs, ultimately yielding the complete 64 codon code via a form of `thermodynamic' selection."

Senior author Kenneth J. Breslauer states in a Rutgers University press release: “These revelations matter because they provide entirely new ways of analyzing the human genome and the genome of any living species, the blueprints of life.” 

Breslauer is Linus C. Pauling Distinguished University Professor in the Department of Chemistry and Chemical Biology in the School of Arts and Sciences at Rutgers University–New Brunswick.

“The origins of the evolution of the DNA genetic code and the evolution of all living species are embedded in the different energy profiles of their molecular DNA blueprints," Breslauer said. "Under the influence of the laws of thermodynamics, this energy code evolved, out of an astronomical number of alternative possibilities, into a nearly singular code across all living species.”

Going forward, the authors propose the creation of a comprehensive energy map of the human genome and the genome of other organisms.