Origins of Life ~ Molecular cooperation?

Of course, a primordial environment that could support RNA synthesis no doubt also spawned many other organic compounds—for example, peptide- and lipid-like molecules, which are chemically much less challenging to generate. “It’s absurd to think that you might have some kind of an environment where you have just a load of nucleotides or RNA in solution, uncontaminated by anything else,” says Lane at University College London.

These molecules would interact with each other, and though they would not have been self-replicating or able to evolve in a Darwinian fashion, one could imagine a different kind of selection driven by the kinetics of the chemical reactions, says Lehman. Under these conditions, he argues, the notion of early life being contingent on a selfish molecule may miss the mark. When it comes to mixtures of interacting molecules, the Darwinian concepts of individual fitness and discrete generations do not apply, he says. “As you approach the origin of life itself, you have to think outside the box a little bit to imagine these systems getting off the ground... The rules of the game are significantly different in the first moments.”

Lehman and others suggest a sort of molecular cooperation as a key factor in the origin of life. Polymers that assembled with other polymers might have been better protected against hydrolysis, for example, and as a result, started growing in number. Over time, these chemical systems could have “evolved” to be more stable and more complex. As more species of molecules joined the interactions, they may have created chemical networks that began to take on functions. “Imagine that, of [a] set of molecules, there might be some that catalyze a chemical reaction that gives rise to a molecule that’s needed—something that’s in short supply, for example,” says Hud. “That would then allow the polymers that are around this ‘generator’ to increase in number. And so there’s a functional sequence.”

To understand the earliest stages of these chemical systems on Earth, a handful of researchers are drawing inspiration from a particular type of deep-sea thermal vents that are alkaline and not too hot. Michael Russell of Caltech’s Jet Propulsion Laboratory in Pasadena, California, predicted that conditions inside such vents would make them favorable sites on early Earth for the abiotic beginning of life. Lane describes the microporous matrix of the vents, through which alkaline fluids chock-full of hydrogen gas flow. Conveniently, these solutions will cluster organic compounds through a process known as thermophoresis. “It’s about the only kind of system I can think of, from a theoretical point of view, which has all the chemical and thermodynamic conditions right that it can produce organics continuously and concentrate them,” says Lane.

Moreover, in the acidic oceans of young Earth, with CO2 levels anywhere from 10 to 1,000 times higher than today’s oceans, such alkaline fluids may well have generated natural proton gradients similar to those that drive ATP production in modern organisms, says Lane. Both Lane and Russell have built prebiotic vent–simulating bioreactors to test these ideas.

Not wanting to limit his search to a subset of geochemical conditions, Powner is taking a different approach: explore all possible chemistries for common conditions that may have yielded the different components of the first molecular systems. “If we want more than RNA, because a plausible living system would likely incorporate more than RNA, we’re probably going to need some form of compounds relating to amino acids, some kind of membrane-forming compounds, something that can recruit and capture energy,” he says. “We need to understand how we can not only build these components, but build them all together.”

One molecule type that has held the attention of Nobel laureate and Harvard Medical School biochemist Jack Szostak for more than a dozen years is fatty acids, which, like the phospholipids of modern cell membranes, have a hydrophobic tail and hydrophilic head. Szostak and others have suggested that genetic molecules and fatty acids might have worked together “to get Darwinian evolutionary processes going that would lead you on a path to modern life,” Szostak says. In vitro work over the past decade has yielded fatty-acid vesicles that can grow and divide under prebiotic conditions, and researchers have even begun to combine these replicating vesicles with genetic elements. “Of course the ultimate goal is we want to have a replicating nucleic acid inside replicating vesicles,” says Szostak, who also holds a position at Massachusetts General Hospital.

An enduring challenge to this achievement, however, has been magnesium, which is necessary for RNA polymerization but causes fatty acids to precipitate out of solution. “For years, that was a big roadblock,” says Szostak. But last November, he and his colleagues came up with a solution: by adding citrate to the mix, the team was able to prevent fatty-acid precipitation while allowing RNA chemistry to proceed as it should.8 “So for the first time we were able to do template-copying experiments where the [RNA was] inside a fatty acid vesicle,” he says. “That’s a big step towards having a complete protocell model.”

As far as pinpointing when “life” emerged from the molecular activity of early Earth, many argue that the endeavor is a bit of a red herring. “Nobody can define what life is, and it’s a pointless question,” Lane says. “Is a virus alive or not? What about a retrotransposon? It’s a continuum between nonliving and living. People tend to draw a line across that continuum which reflects their own interests.”

“[It] is pretty arbitrary,” agrees Szostak, who in 2012 published a short comment on how attempts to define life do not inform the search for its origins.9 “So rather than waste time on a sterile debate, I’d rather just get more experimental work done to try to fill in the gaps in our understanding . . . from planet formation through simple chemistry on a young planet, up to more and more complicated chemistry, and then up to the first cells.”

References

D. Ritson, J.D. Sutherland, “Prebiotic synthesis of simple sugars by photoredox systems chemistry,” Nat Chem, 4:895-99, 2012.F.R. Bowler et al., “Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation,” Nat Chem, 5:383-89, 2013.

A.E. Engelhart et al., “Functional RNAs exhibit tolerance for non-heritable 2’–5’ versus 3’–5’ backbone heterogeneity,” Nat Chem, 5:390-94, 2013.E.J. Hayden et al., “RNA-directed construction of structurally complex and active ligase ribozymes through recombination,” RNA, 11:1678-87, 2005.

N. Vaidya et al., “Recycling of informational units leads to selection of replicators in a prebiotic soup,” Chem Biol, 20:241-52, 2013.

K. Adamala, J.W. Szostak, “Nonenzymatic template-directed RNA synthesis inside model protocells,” Science, 342:1098-1100, 2013.J.W. Szostak, “Attempts to define life do not help to understand the origin of life,” J Biomol Struct Dyn, 29:599-600, 2012.