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May 14, 2009
Chemist Shows How RNA Can Be the Starting Point for Life
By NICHOLAS WADE
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.
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