We are all ultimately evolved from a primordial, chemical-laden soup that gave rise to the first life forms on Earth some 4 billion years ago, or so theory suggests. The most widely accepted timeline of events postulates that billions of years ago RNA molecules self-elevated from this chemical-rich mire containing chemicals and amino acids, which eventually led to the first peptides, and then single-celled organisms. The rest, as they say, is history.

This “RNA-world” timeline underpins the majority of origin-of-life research, but it’s hard to prove. “That theory is so alluring and expedient that most people just don’t think there’s any alternative,” comments Charles Carter, Jr., Ph.D., professor of biochemistry and biophysics at the University of North Carolina (UNC) at Chapel Hill School of Medicine. The UNC Team, working with researchers at the University of Auckland, have now provided what they call “compelling” evidence to suggest that RNA and peptides worked hand in hand to jump-start life on our planet.

“Until now, it has been thought to be impossible to conduct experiments to penetrate the origins of genetics,” says Carter. “But we have now shown that experimental results mesh beautifully with the 'peptide–RNA' theory, and so these experiments provide quite compelling answers to what happened at the beginning of life on Earth.”

The researchers developed this peptide–RNA theory on the back of experiments with two enzyme superfamiles. “Compared to the RNA world hypothesis, what we’ve outlined is simply a much more probable scenario for the origin of life,” states co-researcher Peter Wills, Ph.D., professor of physics at the University of Auckland.

Reporting on their research in Molecular Biology and Evolution (“Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding”) and in Biosystems (“Insuperable Problems of the Genetic Coded Initially Emerging in an RNA World”), the investigators point out that while the scientific world tends to agree on the pathway by which the first cells evolved into plants and animals, we actually don’t know how amino acids first assembled into simple peptides. Carter and Willis claim that RNA couldn’t on its own kick-start the peptide building blocks of life because it lacks “reflexivity”; it cannot enforce the rules by which it is made. Rather, RNA needed peptides to set in motion that reflexive feedback loop that was needed to propagate processes that led to formation of the first living beings.

The peptide–RNA hypothesis is built on experiments with ancient enzyme superfamilies. The results suggest that ancestral versions of these enzymes would have formed reinforcing feedback systems with the earliest genes and proteins, to provide that initial momentum for life forms to develop and increase in complexity.

The 20 the aminoacyl-tRNA synthetase (aaRS) enzymes that make up these superfamilies are still found in all living cells today, and they play a key role in the first stages of protein synthesis. Each aaRS enzyme recognizes a single amino acid and attaches that amino acid to its cognate tRNA.

The aaRSs belong to two structurally distinct families, each containing 10 enzymes. Work published by professor Carter in 2015 showed that the two enzyme ancestors of these two families are actually encoded by opposite, complementary strands of the same gene. This simple arrangement, for just two kinds of amino acids, points to a very ancient origin, he maintains, perhaps at the earliest stages of biology.

The two, highly interdependent but distinct enzymes would have had a stabilizing effect on early biology, the researchers suggest, openig the way for subsequent, ordered diversification of living organisms. “The enforcement of the relationship between genes and amino acids depends on aaRSs, which are themselves encoded by genes and made of amino acids,” Wills notes. “The aaRSs, in turn, depend on that same relationship. There is a basic reflexivity at work here. Theorist Douglas Hofstadter, Ph.D.,  called it a ‘strange loop.’ We propose that this, too, played a crucial role in the self-organization of biology when life began on Earth.”

In effect, the interdependent peptides and the nucleic acids encoding them would have been able to aid each other’s molecular self-organization, “despite the continual random disruptions that beset all molecular processes,” Carter adds. “We believe that this is what gave rise to a peptide–RNA world early in Earth’s history.”

Carter and Wills also suggest that RNA alone is unlikely to have been responsible for setting in molecular organization because of the need for catalysis, on which so many chemical reactions depend. RNA enzymes don’t adjust well to the sorts of temperature changes that would likely have been occurring as the early earth cooled. Only peptide or protein enzymes display that level of catalytic adaptability, Carter suggests.

There would in addition have been “impossible obstacles” blocking progression from a world built solely on RNA, to a protein–RNA world, and then to a planet harboring life. “Such a rise from RNA to cell-based life would have required an out-of-the-blue appearance of an aaRS-like protein that worked even better than its adapted RNA counterpart,” Carter concludes. “That extremely unlikely event would have needed to happen not just once but multiple times—once for every amino acid in the existing gene–protein code. It just doesn’t make sense.”


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