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Chemistry of birth

debate Biologists have long favoured the idea that the first information-carrying molecule of life was not DNA but its close chemical cousin RNA. Nich
Last Updated 11 May 2015, 17:16 IST

It was the actions of Jupiter and Saturn that quite inadvertently created life on Earth. Not the gods of the Roman pantheon, but the giant planets, which once orbited much closer to the sun. Driven outward, they let loose a cascade of asteroids, known as the Late Heavy Bombardment, that blasted the surface of the young Earth and created the deep pockmarks still visible on the face of the moon.

In the intense heat of these impacts, carbon from the meteorites reacted with nitrogen in Earth’s atmosphere to form hydrogen cyanide. Though a deadly poison, cyanide is, nonetheless, the ancient pathway for inert carbon atoms to enter the chemistry of life.

By the time the Late Heavy Bombardment had eased, some 3.8 billion years ago, the cyanide had rained down into pools, reacted with metals, evaporated, been baked and irradiated with ultraviolet light, and dissolved by streams flowing down to a freshwater pool. The chemicals formed from the interactions of cyanide combined there in various ways to generate the precursors of lipids, nucleotides and amino acids. These are the three significant components of a living cell – lipids make the walls of a cell’s various compartments; nucleotides store its information; and amino acids assemble into the proteins that control its metabolism.

All of this is a hypothesis, proposed by John Sutherland, a chemist at the University of Cambridge in England. But he has tested all the required chemical reactions in a laboratory and developed evidence that they are plausible under the conditions expected of primitive Earth.

Having figured out a likely chemistry needed to produce the starting materials of life, John then developed the geological scenario above because it provides the conditions required by the chemistry. As for the chemistry itself, that springs from John’s discovery six years ago of the key to the RNA world.

Biologists have long favoured the idea that the first information-carrying molecule of life was not DNA but its close chemical cousin RNA. RNA can store genetic information and act as an enzyme to create more RNA. Like DNA, RNA is made up of a string of chemical units known as nucleotides. Each nucleotide consists of a sugar, ribose in the case of RNA, joined to a base at one end and to a phosphate group at the other.

Researchers trying to reconstruct the chemistry that led to life had shown plausible ways in which ribose and the bases could have arisen. But in prebiotic chemistry, the assumed natural chemistry of Earth before life began, they could find no likely way of joining ribose to a base. So daunting was this obstacle that some began to doubt the idea of an RNA world, looking instead for a pre-RNA system.

After 10 years of testing every possible combination of prebiotic chemicals, John discovered that the solution was not to build the ribose and the sugar units separately in textbook fashion, but to construct a substance that was part sugar and part base. The addition of another simple chemical converted this hybrid into a ribonucleotide. The door to the RNA world had at last been opened.

If this step was critical, John inferred, then the rest of prebiotic chemistry must somehow be related to it. He and colleagues have spent the last six years doing experiments to see how the ribonucleotide chemistry pathway can be linked back to hydrogen cyanide as its starting point, and how other significant prebiotic chemicals might have emerged from the cyanide-to-nucleotide pathway.

Evidences
So far they have demonstrated ways to generate 12 of the 20 amino acids used in proteins, two of the four ribonucleotides of RNA, and glycerol 1-phosphate, the universal building block of the lipids from which cell membranes are formed. Their findings were reported in March in Nature Chemistry.

Though other researchers have shown how several of these substances could have formed on primitive Earth, these required a variety of conditions, some incompatible. This is the first time that so many significant life chemicals have been shown to emerge from the same chemistry.

John’s report “lays out for the first time a scenario for generating potentially all of the building blocks of life in one geological setting,” said Jack W Szostak, a geneticist at Massachusetts General Hospital who studies the origin of life. “The details of the scenario will be debated for some time, but over all, I think it’s a very big advance,” he said. Jack shared the Nobel Prize in Medicine in 2009 for the discovery of the mechanism that protects the ends of chromosomes.

John’s chemicals cannot all be mixed together at once. His reaction scheme requires them to be delivered in sequence to a central pool. So in his scenario, separate streams flow over mineral deposits and arrive one by one at the pool. Therein lies a possible weakness, Paul J Bracher, a chemist at Saint Louis University in Missouri, said in a commentary in Nature Chemistry. “This new report represents a fantastically interesting approach, but origin-of-life chemists still have plenty of work to do in the kitchen,” he wrote.

Others have deeper reservations. Steven Benner, the director of the Foundation for Applied Molecular Evolution in Gainesville, Florida, said that many of the reactions in John’s scheme “aren’t real,” meaning that pure chemicals might react as proposed in the laboratory, but that the process could not be expected to proceed the same way in a natural mix of chemicals.

Steven also noted that the popular idea of an RNA world is burdened with several unresolved paradoxes. One is that if you have a pool of chemicals and pump energy in, “you don’t get life, you get asphalt,” he said, meaning that the chemicals will react together to form a gooey tar. Another is that water is essential for life, as are nucleotides, but water destroys nucleotides. A third problem is that RNA is assumed to act as an enzyme and as a store of genetic information, but the two roles require contradictory properties: An enzyme must fold up and be reactive, while a genetic molecule should do neither.

The traditional field of prebiotic chemistry has made some headway, in Steven’s view, but not nearly enough to suggest real answers. “Still, to have these very basic problems left hanging suggests that maybe we’re not answering the correct question,” he said.

John is still trying to find plausible routes to the other two RNA nucleotides. He also hopes to understand how the molecules of life could have been built up from their individual units, a process known as polymerisation. “In biology, RNA makes protein and proteins make RNA, so the biology is telling you they work in cahoots with each other,” he said. He added that he did not yet know if polymerisation would take place on a metal surface, often assumed to be a good catalyst, or inside a cell membrane.

Life may still be unlikely, but at least it’s beginning to seem almost possible.

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(Published 11 May 2015, 17:16 IST)

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