Biochemists argue about whether the end of the era of RNA does not come

For decades, the theory of the origin of life with RNA in the main role occupied a leading position. New research can shake confidence in the origin of life based on this theory.

Popular theory claims that life came from a chemical-rich soup in which RNA first began to reproduce itself. But a combination of peptides and RNA may be more effective.

Four billion years ago, circling in the prehistoric chemical soup of Earth, the first molecular precursors of life appeared. And although the exact definition of these molecules remains the topic of irritated disputes, scientists agree that these molecules needed to carry out two basic actions: to preserve information and catalyze chemical reactions. Modern cells transfer these powers, respectively, to DNA and its proteins - but according to the popular explanation prevailing in modern studies of the origin of life and biology textbooks, RNA first played this role, paving the way for DNA and proteins that intercepted these responsibilities later.

This hypothesis, proposed in the 1960s and dubbed the " RNA world " two decades later, is now considered as the most likely explanation for the beginning of life. There are enough alternative “worlds”, but they are usually considered to be reserve theories, illusory flights of imagination and bizarre thought experiments.

Mainly because the hypothesis of the world of RNA is supported by a large number of experimental evidence than its competitors have gained. Last month, we already reported on an alternative theory , according to which protein-like molecules could be the first self-replicating molecules instead of RNA. But these findings were purely computational — then the researchers were just beginning experiments in search of evidence in favor of their statements.

Now, a couple of researchers have put forward another theory — this time including the joint evolution of RNA and peptides — which they hope can shake the foundations of the RNA world.

Why RNA was not enough

Recent work published in the journals Biosystems and Molecular Biology and Evolution , schematically describe evidence that the hypothesis of the world of RNA does not provide sufficient grounds for subsequent evolutionary events. Instead, says Charles Carter , a structural biologist from the University of North Carolina, one of the authors of the work, their model makes a suitable proposal. “A single polymer would never be able to carry out all the processes necessary for what is now characterized by us as part of life,” he adds.


Charles Carter, a structural biologist from the University of North Carolina

And this single polymer could not be RNA, according to research conducted by his team. Catalysis is the main objection against this molecule: some studies have shown that in order for life to start functioning, the mysterious polymer needed to be able to coordinate the speed of chemical reactions that can occur at speeds differing in magnitude by 20 orders of magnitude. Even if RNA somehow managed to do this in the prebiological world, its capabilities as a catalyst would have to adapt to the burning temperatures — on the order of 100 ° C — prevailing in the early Earth. When the planet began to cool, RNA, as Carter claims, would not be able to evolve and maintain synchronization further. A symphony of chemical reactions was soon to fall apart.

Perhaps most importantly, the world with RNA alone does not explain the emergence of the genetic code that the vast majority of living organisms use today to transfer genetic information to proteins. The code takes each of the 64 possible three nucleotide RNA sequences, and combines them with one of the 20 amino acids used to create proteins. In order to select a set of rules that are sufficiently reliable to perform such a task, too much time was needed for RNA alone, says Peter Wills, co-author of Carter from the University of Auckland in New Zealand - if the RNA world could reach such a state that it seems unlikely to him. From the point of view of Wills, RNA could become a catalyst for its own formation, which would make it "chemically reflexive," but it lacked "computational reflexivity."


Peter Wills, biophysicist from the University of Auckland in New Zealand

“A system that uses information like organisms use genetic information — to synthesize their own components — must contain reflective information,” said Wills. Reflexive information, by its definition, is such information that "being encoded into a system, creates components that conduct precisely this particular decoding." RNA from the hypothesis of the world of RNA, he added, is simple chemistry because it is unable to control its chemistry. “The RNA world doesn’t tell you anything about genetics,” he said.

Nature needed to find another way, the best shortcut to creating a genetic code. Carter and Wills believe that they have opened this shortcut. It depends on a small feedback loop that would not grow only from RNA, but could emerge from a complex of peptides and RNA.

Attach peptides

Carter discovered allusions to this complex in the mid-1970s, when the institute learned that certain structures found in most proteins are "right-sided." Atoms in structures could be organized in two equivalent ways that are mirror-like from each other, but all structures use only one method. Most of the nucleic acids that make up DNA and RNA are also right-sided. Carter began to consider RNA and polypeptides as complementary structures, and modeled a complex in which "they were made for each other, like a hand and a glove."

This implies the possibility of elementary coding, the basis for the exchange of information between RNA and polypeptides. He worked on sketches of how this process could look, extrapolating back from the modern, much more complex genetic code. When the hypothesis, which in 1986 was called the "RNA world", gained popularity, Carter, by his own admission, was unsettled. It seemed to him that his world of peptides and RNA, proposed ten years before, had been completely ignored.

Since then, he, Wills, and others have worked together on a theory that goes back to that study. Their main goal was to derive the simplest genetic code that precedes the modern, more specific and complex. Therefore, they turned not only to calculations, but also to genetics.

Their theory is based on 20 “loading” molecules, aminoacyl-tRNA-synthetase . These catalytic enzymes allow RNA to bind to certain amino acids in accordance with the rules of the genetic code. "In a sense, the genetic code is recorded in the characteristics of the active points" of these enzymes, says Jenny Hofmeyr, a biochemist from the University of Stellenbosch in South Africa, who did not participate in the study.

Previous studies have shown that 20 enzymes can be equally divided into two groups of 10 each based on their structure and sequences. These two classes of enzymes possess specific sequences that encode mutually exclusive amino acids — that is, these enzymes should have emerged from the complementary chains of a single ancient gene. Carter, Wills, and their colleagues discovered that in this case RNA encoded peptides using a set of just two rules (or, in other words, used two types of amino acids). The resulting peptides maintained the same rules that govern the transfer process, which results in a feedback loop that is key to this theory.


RNA peptide world

Life could have come from the interaction of RNA and peptides that worked as the first genetic code. A self-sustaining loop of reactions would create enzymes, choosing from just two types of amino acids instead of 20 types found in modern proteins.

1) "Load enzymes" coincide with the sequences of bases in RNA and help create peptide chains from the associated amino acids of the first (red) and second (green) class
2) The chains of peptides fold into functional forms.
3) Depending on the form of the chain, amino acids of the first or second class are selected and become active load enzymes.
4) Enzymes interact with RNA and deliver amino acids to forming chains.

Gödel's theorem and the chemistry of life

Carter sees a lot of similarity between this loop and the loop in mathematics described by the philosopher and mathematician Kurt Godel , whose incompleteness theorem postulates that statements in any logical system must appear that cannot be proved or disproved by the means of the system itself. “I think that the analogy with Godel's theorem gives a pretty strong argument in favor of inevitability,” said Carter.

In recent works, Carter and Wills show that their peptide-RNA world solves problems with gaps in the history of the origin of life, which only one RNA cannot explain. “They provide robust theoretical and experimental evidence that RNA and peptides jointly participated in the genesis of the genetic code from the very beginning,” Hofmeyr said, “and that metabolism, creation through copying, transfer and reproduction, should have evolved together.”



Of course, the Carter-Wills model begins with a genetic code, the existence of which involves complex chemical reactions, which include molecules such as transport RNA and stress enzymes. The researchers claim that the events preceding the scenario proposed by them involved the interaction of RNA and peptides. However, this assumption leaves many open questions about how this chemistry started and how it looked.

To answer these questions, there are many theories that go far beyond the RNA world. Some scientists even use the opposite approach from Carter and Wills: they believe that the earliest stages in the development of life do not have to resemble the chemistry that exists today. Doron Lancet , a genome researcher at the Wiseman Science Institute in Israel, offers an alternative theory based on the assembly of lipids that catalyze the entry and exit of various molecules. Information is transmitted not by genetic sequences, but by lipid compositions.

Like the Carter-Wills model, the idea of ​​the Lancet includes not one type of molecules, but a huge number of them. “More and more evidence is gathered,” says the Lancet, “able to confirm this alternative hypothesis.” So far, scientists have not decided what exactly happened at the origins of life, but, apparently, they are beginning to move away from the story in which there was only RNA. “We need to put only a few eggs in the basket with RNA,” said Hofmeyr.