Article  The evolving story of how chemistry became biology

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https://www.quantamagazine.org/the-evolv...-20261112/

EXCERPTS: By the mid-20th century, it became possible to probe life’s origins through chemistry, molecular biology, and genetics. Hypotheses exploded. Scientists clashed over which type of molecule — RNA, lipids, proteins, and metabolites are prime suspects — could have started it all. The arguments have gone on for so long, without resolution or unifying insight, that some experts have considered the field to be in crisis.

“There’s nothing more exciting for a scientific field than a moment of crisis,” said Betül Kaçar(opens a new tab), an astrobiologist and evolutionary biologist at the University of Wisconsin, Madison. “That’s when I think breakthroughs happen.”

[...] To study the emergence of lifelike biochemical systems, biologists are now pushing backward into the past from the living world with new genetic tricks, while chemists are pushing forward from the nonliving world with new and strange mixtures of molecules. And by combining tools from chemistry and biology, synthetic biologists are embracing informed speculation and probing novel biological systems that may not have ever existed. Scientists now engaged with the origins of life are asking not just what life is, but what it does — on an archaic world, in a lab dish, or somewhere beyond our atmosphere.

[...] One way to approach how life started is to think like the chemists: Start with nonliving molecules and bring them to life. Another way is to think like an evolutionary biologist: Trace life backward to its most ancient root, and perhaps beyond.

If you were to take everything that’s alive today — from blooming flowers and trees to humans and dogs to single cells encrusting a hydrothermal vent — and trace every lineage back through billions of years, you’d eventually reach a single point. This cell, from which all life known to us has descended, is the root of the tree of life.

In the 1990s, this cell (or, more accurately, this population of cells) got a name: the “last universal common ancestor,” or LUCA. Biologists debated who or what LUCA was: whether it resembled a modern cell or was something simpler. LUCA left no fossils — the oldest uncontested ancient fossils date to around 3.5 billion years ago — but it has left a different material record from billions of years ago.

“There are only two records of past life,” said Greg Fournier, an evolutionary biologist at the Massachusetts Institute of Technology. One is dead remains of ancient organisms fossilized in the rock record. The second, he said, is “the record within genomes … traces that have been passed down from the first cells to all life or almost all life alive today.”

[...] They reported that LUCA likely operated with around 2,600 proteins(opens a new tab) encoded by a genome comparable in size to those in modern-day bacteria. Those genes and proteins suggested that LUCA had a basic metabolism, a functional cell membrane, and even a primitive immune system for fighting viruses. It had all the basic equipment for making energy, replicating DNA, and producing proteins. Altogether, the analysis painted a picture of an already complex organism.

“LUCA was a fully flesh, swimming, eating, reproducing, messy cell,” Kaçar said. And wherever it lived, it likely didn’t live alone.

Donoghue’s team found that LUCA had a metabolic pathway that is nearly identical to one found in modern microbes, known as the Wood-Ljungdahl pathway. Intriguingly, this metabolic pathway is related to another metabolic process, acetogenesis, that cannot work on its own but relies on the processes of other cells: LUCA’s neighbors. This makes it very likely that LUCA was part of a larger community or ecosystem containing multiple types of early cells.

Donoghue’s team also estimated an age for LUCA’s lineage: 4.2 billion years old. Given that the planet is thought to have cooled enough to become habitable around 4.4 billion years ago, LUCA’s community must have evolved in the blink of an evolutionary eye. “Life gets going pretty fast when the conditions are favorable,” Masel said.

If LUCA was already a complex population and included many types of cells, then a meaningful portion of life’s early evolutionary history must have occurred well before it lived. By then, the available molecular and cellular diversity must have gone far beyond the basic rudiments of life; it was enough for evolutionary processes to have selected for complex molecular machines and systems.

This revelation has compelled some biologists, who by definition study life forms that evolved after LUCA, to shift their target to the life forms, quasi-life forms, and lifelike processes that may have existed before LUCA. They’re using new tools to push beyond the material record’s limits to predict how this cellular ecosystem might have evolved in the prebiotic soup.

[...] The time period before LUCA is so fuzzy that we don’t even know if life then was built using the same ingredients that life uses today. After billions of years of evolution, modern biology could have changed significantly. Evolution is not a designer; the systems that stuck were those that worked, not necessarily the optimal ones for the job. Plus, early organisms led a very different life in a very different environment more than 4 billion years ago; different materials may have been available or may have worked more effectively there.

[...] Maybe, during life’s pre-LUCA years, proteins were built with more or fewer amino acids, or even with a totally different set. “Computationally, we think that yes — life could have used different amino acids,” Hlouchová said. “We know that our amino acids were easily available, at least the half of them, and they would be very accessible to prebiotic synthesis on planets which would be similar to ours.” And on a different planet, with different chemistry, she said, “you could have different amino acids and … you could eventually build life using different ways.”

[...] Life is made up of not only molecules but functions. It can replicate, it can metabolize, and it can evolve. These functions don’t necessarily need to be performed by the same molecules that life uses today.

[...] It took Otto’s lab another 10 years to figure out how to get their self-replicating molecules to catalyze reactions(opens a new tab) other than their own replication, such as those that helped them make their own precursors. Then, in still unpublished work, they altered some of the molecules in a way that compelled the rings to form compartments that grew and divided. “It’s replicating, it’s metabolizing, it’s keeping itself together in a compartment,” Otto said. Eventually the “benzene cells” grew big enough to be seen under a microscope, he said.

But does that make them alive? The only thing they’re really missing, from a functional perspective, is the ability to evolve, Otto said. That’s where his lab is headed(opens a new tab) next. “We’re trying to make something that starts to approach life,” he said. “But it will be on a life support machine for some time to come.”

His benzene “cells” are a far cry from life as we know it. But if you can figure out conceptually how evolution could arise, Otto argued, you can reenact that mechanism, under the simulated conditions of the early Earth and with your favorite prebiotic molecules. “I think, then, you’re closer to the origin,” Otto said.

[...] To this day, no one has convincingly re-created life — self-sustaining, self-replicating, independently evolving — in the lab. Researchers aren’t even sure whether evolutionary processes on the early Earth, in systems of molecules that may or may not have been “alive,” would look like those that drive adaptive changes in cells or organisms today.

But give the scientists a little more time to work on the problem. “Our great chemists, only a handful of them, are doing this in the lab, and with only a few test tubes over a [a few] decades,” said Michael Lynch(opens a new tab), an evolutionary biologist at Arizona State University who is working with Kaçar, Travisano, and others to bring evolutionary rules(opens a new tab) to the origins-of-life field. In comparison, prebiotic chemistry on early Earth had a few hundred million years, which is “an awful long time for life to experiment.”

Similar experiments could be taking place somewhere out there right now. Our galaxy alone has at least 6,000 known exoplanets and likely many, many more... (MORE - missing details)
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