How to Build Life in a Pre-Darwinian World

How did life’s myriad parts come together? At a minimum, the first life forms on Earth needed a way to store information and replicate. Only then could they make copies of themselves and spread across the world.

One of the most influential hypotheses states that it all began with RNA, a molecule that can both record genetic blueprints and trigger chemical reactions. The “RNA world” hypothesis comes in many forms, but the most traditional holds that life started with the formation of an RNA molecule capable of replicating itself. Its descendants evolved the ability to perform an array of tasks, such as making new compounds and storing energy. In time, complex life followed.

However, scientists have found it surprisingly challenging to create self-replicating RNA in the lab. Researchers have had some success, but the candidate molecules they have manufactured to date can only replicate certain sequences or a certain length of RNA. Moreover, these RNA molecules are themselves quite complicated, raising the question of how they might have formed through chance chemical means.

Nick Hud, a chemist at the Georgia Institute of Technology, and his collaborators are looking beyond biology to the role of chemistry in the development of life. Perhaps before biology arose, there was a preliminary stage of proto-life, in which chemical processes alone created a smorgasbord of RNAs or RNA-like molecules. “I think there were a lot of steps before you get to a self-replicating self-sustaining system,” Hud said.

In this scenario, a variety of RNA-like molecules could form spontaneously, helping the chemical pool to simultaneously invent many of the parts needed for life to emerge. Proto-life forms experimented with primitive molecular machinery, sharing their parts. The entire system worked like a giant community swap meet. Only once this system was established could a self-replicating RNA emerge.

At the heart of Hud’s proposal is a chemical means for generating a rich diversity of proto-life. Computer simulations show that certain chemical conditions can produce a varied collection of RNA-like molecules. And the team is currently testing the idea with real molecules in the lab; they hope to publish the results soon.

Hud’s group is leading the way for a number of researchers who are challenging the traditional RNA-world hypothesis and its reliance on biological rather than chemical evolution. In the traditional model, new molecular machinery was created using biological catalysts, known as enzymes, as is the case in modern cells. In Hud’s proto-life stage, myriad RNA or RNA-like molecules could form and change through purely chemical means. “Chemical evolution could have helped life get started without enzymes,” Hud said.

Hud and his collaborators have taken this idea one step further, suggesting that the ribosome, the only piece of biological machinery that is found in all living things today, emerged through chemistry alone. That’s an unconventional thought to many in the field, who think that the ribosome was born of biology.

If Hud’s team can create proto-life forms under conditions that might have existed on the early Earth, it would suggest that chemical evolution may have played a much more significant role in the origins of life than scientists expected. “Maybe there was some simpler form of evolution that preceded Darwinian evolution,” said Niles Lehman, a biochemist at Portland State University in Oregon.

The Pre-Darwinian World

When most people think about evolution, they think about Darwinian evolution, in which organisms compete with one another for limited resources and pass on genetic information to their offspring. Each generation undergoes genetic tweaks, and the most successful progeny survive to pass along their own genes. That mode of evolution dominates life today.

Carl Woese, a renowned biologist who gave us the modern tree of life, believed that the Darwinian era was preceded by an early phase of life governed by very different evolutionary forces. Woese thought it would have been nearly impossible for an individual cell to spontaneously come up with everything it needed for life. So he envisioned a rich diversity of molecules engaged in a communal existence. Rather than competing with each other, primitive cells shared the molecular innovations they invented. Together, the pre-Darwinian pool created the components needed for complex life, priming the early Earth for the emergence of the magnificent menagerie we see today.

Hud’s model takes Woese’s pre-Darwinian vision even further back in time, providing a chemical means for producing the molecular diversity that primitive cells needed. One proto-life form might have developed a way to make the building blocks it needed to make more of itself, while another might have found a way to harvest energy. The model differs from the traditional RNA-world hypothesis in its reliance on chemical rather than biological evolution.

According to RNA world, the first RNA molecules replicated themselves using a built-in enzyme called a ribozyme that was made of RNA. In Hud’s proto-life world, that task is accomplished through purely chemical means. The story begins with a chemical soup of RNA-like molecules. Most of these would have been short, as short strands are more likely to form spontaneously, but a few longer, more complex molecules might have come together as well. Hud’s model describes how the longer molecules might have replicated without the aid of an enzyme.

In Hud’s vision of a prebiotic world, the primordial RNA soup underwent regular cycles of heating and cooling in a thick, viscous solution. Heat separated the bound pairs of RNA, and the viscous solution kept the separated molecules apart for a while. In the interim, small segments of RNA, just a few letters in length, stuck to each long strand. The small segments eventually got sewn together, forming a new strand of RNA that matched the original long strand. The cycle then began again.

Over time, a pool of varied RNA-like molecules would have accumulated, some of them capable of simple functions, such as metabolism. And just like that, purely chemical reactions would have produced the molecular diversity needed to create Woese’s pre-Darwinian cornucopia of proto-life.

Hud’s team has been able to carry out the first stages of the replication process in the laboratory, although they can’t yet glue together the short segments without resorting to biological tools. If they can get over that hurdle, they’ll have created a versatile way of replicating any RNA that pops up.

Yet some scientists are skeptical that chemically mediated replication could work well enough to produce the pre-Darwinian world Hud describes. “I don’t know whether I believe it,” said Paul Higgs, a biophysicist at McMaster University in Hamilton, Ontario, who studies the origins of life. “It would have to be sufficiently accurate and rapid to pass on the sequence” — that is, it would need to produce new RNAs more quickly than they broke down and with enough fidelity to create near copies of the template molecule.

Chemical change on its own wouldn’t have been enough to trigger the emergence of life. The pool of proto-life would also have needed some kind of selection to make sure that useful molecules succeeded and multiplied. In their model, Hud’s team proposes that very simple proto-enzymes might have spread if they did something helpful for their maker and the larger community. For example, an RNA molecule that made more of its own building blocks would benefit itself and its neighbors by providing additional raw materials for replication. In computer simulations that Hud’s team performed, this type of molecule did indeed take root. “If a sequence comes along that does something useful, it can then be enriched in the pool,” Hud said.

Ribosomal Roots

One possible glimpse of the pre-Darwinian world can be seen in the ribosome, an ancient piece of molecular machinery that lies at the heart of our genetic code. It is an enzyme that translates RNA, which encodes genetic information, into proteins, which carry out the many chemical reactions in our cells.

The core of the ribosome is made of RNA. This feature makes the ribosome unique — the vast majority of enzymes in our cells are made from proteins. Both the ribosomal core and the genetic code are shared among all living things, suggesting that they were present very early in the evolution of life, perhaps before it crossed the Darwinian threshold.

Hud and his collaborator Loren Williams, also at Georgia Tech, point to the ribosome as support for their chemically dominated world. In a paper published last year, they made the controversial proposal that the core of the ribosome was created via chemical evolution. They also suggested that it arose before the first self-replicating RNA molecule. Perhaps the ribosomal core was a successful experiment in chemical evolution, they said. And after it took root in the pre-Darwinian soup, it crossed the Darwinian threshold and became an essential part of all life.

Their argument centers on the relative simplicity of the ribosomal core, more formally known as the peptidyl transferase center (PTC). The PTC’s job is to bring together amino acids, the building blocks of proteins. Unlike traditional enzymes, which speed up chemical reactions by using “fancy chemical tricks,” as Lehman put it, it works almost like a dehydrator. It coaxes two amino acids to bond simply by removing a molecule of water. “It’s kind of a poor way to drive a reaction,” Lehman said. “Protein enzymes typically rely on more powerful chemical strategies.”

Lehman notes that simplicity likely preceded power in the earliest stages of life. “When thinking about the origins of life, you have to think about simple chemistry first; any process with simple chemistry is probably going to be ancient,” he said. “I think that’s more powerful evidence than the fact that it’s [shared] among all life.”

Despite the powerful evidence, it’s still hard to imagine how the ribosomal core could have been created by chemical evolution. An enzyme that makes more of itself — like the replicator RNA of the RNA-world hypothesis — automatically creates a feedback loop, continually boosting its own production. By contrast, the ribosomal core doesn’t produce more ribosomal cores. It produces random chains of amino acids. It’s unclear how this process would encourage the production of more ribosomes. “Why would making random peptides make that thing better?” Higgs said.

Hud and his collaborators propose that RNA and proteins evolved in tandem, and those that figured out how to work together survived best. This idea lacks the simplicity of the RNA world, which posits a single molecule capable of both encoding information and catalyzing chemical reactions. But Hud suggests that facility might trump elegance in the emergence of life. “I think there’s been an overemphasis on what we call simplicity, that one polymer is simpler than two,” he said. “Maybe it’s easier to get certain reactions going if two polymers work together. Maybe it’s simpler for polymers to work together from the start.”

This article was reprinted on TheAtlantic.com.