[Infowarrior] - Chemist Shows How RNA Can Be the Starting Point for Life

[Richard Forno]

May 14, 2009
Chemist Shows How RNA Can Be the Starting Point for Life
By NICHOLAS WADE
http://www.nytimes.com/2009/05/14/science/14rna.html?hpw=&pagewanted=print

An English chemist has found the hidden gateway to the RNA world, the  
chemical milieu from which the first forms of life are thought to have  
emerged on earth some 3.8 billion years ago.

He has solved a problem that for 20 years has thwarted researchers  
trying to understand the origin of life — how the building blocks of  
RNA, called nucleotides, could have spontaneously assembled themselves  
in the conditions of the primitive earth. The discovery, if correct,  
should set researchers on the right track to solving many other  
mysteries about the origin of life. It will also mean that for the  
first time a plausible explanation exists for how an information- 
carrying biological molecule could have emerged through natural  
processes from chemicals on the primitive earth.

The author, John D. Sutherland, a chemist at the University of  
Manchester, likened his work to a crossword puzzle in which doing the  
first clues makes the others easier. “Whether we’ve done one across is  
an open question,” he said. “Our worry is that it may not be right.”

Other researchers say they believe he has made a major advance in  
prebiotic chemistry, the study of the natural chemical reactions that  
preceded the first living cells. “It is precisely because this work  
opens up so many new directions for research that it will stand for  
years as one of the great advances in prebiotic chemistry,” Jack  
Szostak of the Massachusetts General Hospital wrote in a commentary in  
Nature, where the work is being published on Thursday.

Scientists have long suspected that the first forms of life carried  
their biological information not in DNA but in RNA, its close chemical  
cousin. Though DNA is better known because of its storage of genetic  
information, RNA performs many of the trickiest operations in living  
cells. RNA seems to have delegated the chore of data storage to the  
chemically more stable DNA eons ago. If the first forms of life were  
based on RNA, then the issue is to explain how the first RNA molecules  
were formed.

For more than 20 years researchers have been working on this problem.  
The building blocks of RNA, known as nucleotides, each consist of a  
chemical base, a sugar molecule called ribose and a phosphate group.  
Chemists quickly found plausible natural ways for each of these  
constituents to form from natural chemicals. But there was no natural  
way for them all to join together.

The spontaneous appearance of such nucleotides on the primitive earth  
“would have been a near miracle,” two leading researchers, Gerald  
Joyce and Leslie Orgel, wrote in 1999. Others were so despairing that  
they believed some other molecule must have preceded RNA and started  
looking for a pre-RNA world.

The miracle seems now to have been explained. In the article in  
Nature, Dr. Sutherland and his colleagues Matthew W. Powner and  
Béatrice Gerland report that they have taken the same starting  
chemicals used by others but have caused them to react in a different  
order and in different combinations than in previous experiments. they  
discovered their recipe, which is far from intuitive, after 10 years  
of working through every possible combination of starting chemicals.

Instead of making the starting chemicals form a sugar and a base, they  
mixed them in a different order, in which the chemicals naturally  
formed a compound that is half-sugar and half-base. When another half- 
sugar and half-base are added, the RNA nucleotide called ribocytidine  
phosphate emerges.

A second nucleotide is created if ultraviolet light is shined on the  
mixture. Dr. Sutherland said he had not yet found natural ways to  
generate the other two types of nucleotides found in RNA molecules,  
but synthesis of the first two was thought to be harder to achieve.

If all four nucleotides formed naturally, they would zip together  
easily to form an RNA molecule with a backbone of alternating sugar  
and phosphate groups. The bases attached to the sugar constitute a  
four-letter alphabet in which biological information can be represented.

“My assumption is that we are here on this planet as a fundamental  
consequence of organic chemistry,” Dr. Sutherland said. “So it must be  
chemistry that wants to work.”

The reactions he has described look convincing to most other chemists.  
“The chemistry is very robust — all the yields are good and the  
chemistry is simple,” said Dr. Joyce, an expert on the chemical origin  
of life at the Scripps Research Institute in La Jolla, Calif.

In Dr. Sutherland’s reconstruction, phosphate plays a critical role  
not only as an ingredient but also as a catalyst and in regulating  
acidity. Dr. Joyce said he was so impressed by the role of phosphate  
that “this makes me think of myself not as a carbon-based life form  
but as a phosphate-based life form.”

Dr. Sutherland’s proposal has not convinced everyone. Dr. Robert  
Shapiro, a chemist at New York University, said the recipe “definitely  
does not meet my criteria for a plausible pathway to the RNA world.”  
He said that cyano-acetylene, one of Dr. Sutherland’s assumed starting  
materials, is quickly destroyed by other chemicals and its appearance  
in pure form on the early earth “could be considered a fantasy.”

Dr. Sutherland replied that the chemical is consumed fastest in the  
reaction he proposes, and that since it has been detected on Titan  
there is no reason it should not have been present on the early earth.

If Dr. Sutherland’s proposal is correct it will set conditions that  
should help solve the many other problems in reconstructing the origin  
of life. Darwin, in a famous letter of 1871 to the botanist Joseph  
Hooker, surmised that life began “in some warm little pond, with all  
sorts of ammonia and phosphoric salts.” But the warm little pond has  
given way in recent years to the belief that life began in some exotic  
environment like the fissures of a volcano or in the deep sea vents  
that line the ocean floor.

Dr. Sutherland’s report supports Darwin. His proposed chemical  
reaction take place at moderate temperatures, though one goes best at  
60 degrees Celsius. “It’s consistent with a warm pond evaporating as  
the sun comes out,” he said. His scenario would rule out deep sea  
vents as the place where life originated because it requires  
ultraviolet light.

A serious puzzle about the nature of life is that most of its  
molecules are right-handed or left-handed, whereas in nature mixtures  
of both forms exist. Dr. Joyce said he had hoped an explanation for  
the one-handedness of biological molecules would emerge from prebiotic  
chemistry, but Dr. Sutherland’s reactions do not supply any such  
explanation. One is certainly required because of what is known to  
chemists as “original syn,” referring to a chemical operation that can  
affect a molecule’s handedness.

Dr. Sutherland said he was working on this problem and on others,  
including how to enclose the primitive RNA molecules in some kind of  
membrane as the precursor to the first living cell.