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New Glimpses of Life’s Puzzling Origins

by RebelSnake | Published on November 17th, 2006, 12:22 pm | Science
Critical Pairing
Origin of life: the search for the first genetic material

How did life originate on Earth? Until now, there have only been theories to answer this question. One of the fundamental steps leading to living organisms is the development of molecules that can replicate and multiply themselves—the first genetic material. A team led by Ramanarayanan Krishnamurthy and Albert Eschenmoser at The Scripps Research Institute in La Jolla, California, is researching how this molecule might have looked.

Our own genetic material is DNA. Its backbone is made of sugar and phosphate building blocks. Like a strand of pearls, the four “letters” of the genetic code are arranged along this backbone. Two complementary strands of DNA form a double helix because the purine bases adenine (A) and guanine (G) form specific pairs with the pyrimidine bases thymine (T) and cytosine (C), attaching to each other through two or three docking sites. This type of structure could also be the basis for the first genetic material. However, it is doubtful that its backbone consisted of sugar and phosphate; it may have consisted of peptide-like building blocks. Amino acids, from which peptides are made, were already present in the “primordial soup”. However, the bases may also have looked different in their primitive form.

To find the right track in searching for the origins of life, the team is trying to put together groups of potential building blocks from which primitive molecular information transmitters could have been made. The researchers have taken a pragmatic approach to their experiments. Compounds that they test do not need to fulfill specific chemical criteria; instead, they must pass their “genetic information” on to subsequent generations just as simply as the genetic molecules we know today—and their formation must have been possible under prebiotic conditions. Experiments with molecules related to the usual pyrimidine bases (pyrimidine is a six-membered aromatic ring containing four carbon and two nitrogen atoms), among others, seemed a good place to start. The team thus tried compounds with a triazine core (a six-membered aromatic ring made of three carbon and three nitrogen atoms) or aminopyridine core (which has an additional nitrogen- and hydrogen-containing side group). Imitating the structures of the normal bases, the researchers equipped these with different arrangements of nitrogen- and hydrogen- and/or oxygen-containing side groups.

Unlike the usual bases, these components can easily be attached to many different types of backbone, for example, a backbone made of dipeptides or other peptide-like molecules. In this way, the researchers did indeed obtain molecules that could form specific base pairs not only with each other, but also with complementary RNA and DNA strands. Interestingly, only one sufficiently strong pair was formed within both the triazine and aminopyridine families; however, for a four-letter system analogous to the ACGT code, two such strongly binding pairs are necessary. “Our results indicate that the structure of the bases, rather than the structure of the backbone, was the critical factor in the development of our modern genetic material,” says Krishnamurthy. Many chain molecules are able to adopt a suitable spatial structure, but only a few bases can enter into the necessary specific pairing. In this, our alternative bases are clearly inferior to the usual Watson–Crick bases. “Based on our observations, we are beginning to understand why the natural bases are optimal with regard to the function they perform.”
"It is incredible that primitive humans guessed wrongly about everything else, but discovered the truth about the origin of life."

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November 30th, 2006, 11:36 am
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New Glimpses of Life’s Puzzling Origins

Some 3.9 billion years ago, a shift in the orbit of the Sun’s outer planets sent a surge of large comets and asteroids careening into the inner solar system. Their violent impacts gouged out the large craters still visible on the Moon’s face, heated Earth’s surface into molten rock and boiled off its oceans into an incandescent mist.

Yet rocks that formed on Earth 3.8 billion years ago, almost as soon as the bombardment had stopped, contain possible evidence of biological processes. If life can arise from inorganic matter so quickly and easily, why is it not abundant in the solar system and beyond? If biology is an inherent property of matter, why have chemists so far been unable to reconstruct life, or anything close to it, in the laboratory?
In the last few years, however, four surprising advances have renewed confidence that a terrestrial explanation for life’s origins will eventually emerge.

One is a series of discoveries about the cell-like structures that could have formed naturally from fatty chemicals likely to have been present on the primitive Earth. This lead emerged from a long argument between three colleagues as to whether a genetic system or a cell membrane came first in the development of life. They eventually agreed that genetics and membranes had to have evolved together.
Dr. Szostak’s experiments have come close to creating a spontaneously dividing cell from chemicals assumed to have existed on the primitive Earth. But some of his ingredients, like the nucleotide building blocks of nucleic acids, are quite complex. Prebiotic chemists, who study the prelife chemistry of the primitive Earth, have long been close to despair over how nucleotides could ever have arisen spontaneously.

Nucleotides consist of a sugar molecule, like ribose or deoxyribose, joined to a base at one end and a phosphate group at the other. Prebiotic chemists discovered with delight that bases like adenine will easily form from simple chemicals like hydrogen cyanide. But years of disappointment followed when the adenine proved incapable of linking naturally to the ribose.

Last month, John Sutherland, a chemist at the University of Manchester in England, reported in Nature his discovery of a quite unexpected route for synthesizing nucleotides from prebiotic chemicals. Instead of making the base and sugar separately from chemicals likely to have existed on the primitive Earth, Dr. Sutherland showed how under the right conditions the base and sugar could be built up as a single unit, and so did not need to be linked.
Once a self-replicating system develops from chemicals, this is the beginning of genetic history, since each molecule carries the imprint of its ancestor. Dr. Crick, who was interested in the chemistry that preceded replication, once observed, “After this point, the rest is just history.”

Dr. Joyce has been studying the possible beginning of history by developing RNA molecules with the capacity for replication. RNA, a close cousin of DNA, almost certainly preceded it as the genetic molecule of living cells. Besides carrying information, RNA can also act as an enzyme to promote chemical reactions. Dr. Joyce reported in Science earlier this year that he had developed two RNA molecules that can promote each other’s synthesis from the four kinds of RNA nucleotides.

“We finally have a molecule that’s immortal,” he said, meaning one whose information can be passed on indefinitely. The system is not alive, he says, but performs central functions of life like replication and adapting to new conditions.
Prebiotic chemists have long been at a loss to explain how the first living systems could have extracted just one kind of the handed chemicals from the mixtures on the early Earth. Left-handed nucleotides are a poison because they prevent right-handed nucleotides linking up in a chain to form nucleic acids like RNA or DNA. Dr. Joyce refers to the problem as “original syn,” referring to the chemist’s terms syn and anti for the structures in the handed forms.

The chemists have now been granted an unexpected absolution from their original syn problem. Researchers like Donna Blackmond of Imperial College London have discovered that a mixture of left-handed and right-handed molecules can be converted to just one form by cycles of freezing and melting.

With these four recent advances — Dr. Szostak’s protocells, self-replicating RNA, the natural synthesis of nucleotides, and an explanation for handedness — those who study the origin of life have much to be pleased about, despite the distance yet to go. “At some point some of these threads will start joining together,” Dr. Sutherland said. “I think all of us are far more optimistic now than we were five or 10 years ago.”

A lot of applied chemistry there.

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June 18th, 2009, 9:15 am
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