Sunday, December 31, 2006

Clues to the origins of life

The question of how life originated on Earth is one of the really big open questions for science. Right up there with questions like how the universe itself started and how the human mind works.

Questions about how life began have been asked for a long time, of course. But only within roughly the last 50 years, since DNA and related biochemistry began to be understood, has it been possible to address such questions scientifically.

DNA, and its very close relative RNA, provide the framework for one essential of life: the storage of information, which allows for "blueprints" that describe a living organism to be conveniently encoded, so that individual organisms can be duplicated and, ultimately, evolve into more complex organisms. We now understand pretty well how DNA and RNA work, so one key question now is – how did DNA and RNA, the carriers of genetic information, come about?

DNA and RNA are made up of relatively simple organic molecules – sugars and phosphate groups that can polymerize to form a backbone, and a small number of bases which encode information by the way they are ordered in their attachment to the backbone. The information encoded in DNA details how to make proteins, which are also polymeric organic molelcules, consisting of amino acids attached to each other in a sequence specified (mostly) by the DNA. It is the proteins that make up the bulk of the cellular machinery that constitutes a stand-alone single-celled organism, or by grouping together makes a multi-celled organism. So a large part of the question of life's origins comes down to that of how these various organic chemicals came to exist.

In addition to the organic chemicals that make up an organism, another necessity of life is the ability to utilize energy that is ultimately obtained from the environment. In most cases, this energy is derived from sunlight, although in a few rare cases it can come from radioactive elements. Either way, an organism needs to tap into the environmental energy in order to drive chemical reactions which power cellular mechanisms that enable reproduction, locomotion, and (in multicellular organisms) growth. (More complex organisms can also derive their energy from "food", in the form of simpler organisms that have stored up environmental energy obtained more directly.) So another key question is: when and how did these energy-management processes come about?

There have been recent research findings that are relevant to various of these questions.

Let's consider the origins of organic compounds first. One line of thinking is that organic compounds were primarily synthesized from inorganic compounds in natural processes here on Earth. The names Aleksandr Oparin and J. B. S. Haldane are associate with this idea. The classic experiment testing the idea is known as the Miller-Urey experiment, after Stanley Miller and Harold Urey, and was first conducted in 1953, the same year that the structure of DNA was identified by Francis Crick and James Watson. As yet, this is still just a conjectural possibility.

An alternative scenario for the origins of organic compounds is that some simple ones formed in space, which is known to happen, and that some of the basic building blocks of life, such as amino acids, were introduced to Earth on meteorites. This possibility has gained more plausibility from the recently announced finding of apparent "organic materials" in a meteorite that fell in 2000.

NASA Scientists Find Primordial Organic Matter In Meteorite
In a paper published in the Dec. 1 issue of the journal Science, the team, headed by NASA space scientist Keiko Nakamura-Messenger, reports that the Tagish Lake meteorite contains numerous submicrometer hollow organic globules.

Because the meteorite immediately became frozen in ice after it landed, the possibility of contamination from terrestrial material was minimized. Further, the isotopic composition of hydrogen and nitrogen in the globules is quite unlike what is normally found on Earth. It also appears that the material in the meteorite formed at least 4.5 billion years ago – before the Earth and the other planets themselves.
"The isotopic ratios in these globules show that they formed at temperatures of about -260° C, near absolute zero," said Scott Messenger, NASA space scientist and co-author of the paper. "The organic globules most likely originated in the cold molecular cloud that gave birth to our Solar System, or at the outermost reaches of the early Solar System."

Additional references:

Just about two weeks later, results from a completely different souce appeared that also showed the existence of organic compounds in primorial solar system material. This was from the Stardust mission to retrieve grains of matter from the comet 81P/Wild-2:

Comets hold life chemistry clues
Scientists studying the tiny grains of material recovered from Comet Wild-2 by Nasa's Stardust mission have found large, complex carbon-rich molecules.

They are of the type that could have been important precursor components of the initial reactions that gave rise to the planet's biochemistry.

Unlike the case with the Tagish Lake meteorite, it was possible to identify many of the organic compounds in the returned material:
These Wild-2 compounds lack the aromaticity, or carbon ring structures, frequently found in meteorite organics. They are very rich in oxygen and nitrogen, and they probably pre-date the existence of our Solar System.

"It's quite possible that what we're seeing is an organic population of molecules that were made when ices in the dense cloud from which our Solar System formed were irradiated by ultraviolet photons and cosmic rays," Dr Sandford explained.

"That's of interest because we know that in laboratory simulations where we irradiate ice analogues of types we know are out there, these same experiments produce a lot of organic compounds, including amino acids and a class of compounds called amphiphiles which if you put them in water will spontaneously form a membrane so that they make little cellular-like structures."

Additional information from the special Stardust issue of Science (December 15, 2006 – sub. rqd. for full access):

Although these results indicate that organic material formed in or before the earliest stages of the solar system might have seeded organic chemistry on Earth, there is as yet no evidence that this actually is how it happened. An even more radical possibility is that actual living carbon-based organisms that originated outside of our solar system "transplanted" life to Earth. This idea is known as panspermia, but so far, there's little or no credible evidence for it. Short of that, we know at least that the organic compounds for life either originated on Earth or arrived from outside.

So let's move on and turn to the question of how the earliest organisms managed energy supplies in order to reproduce and move. Every organism on Earth that produces energy from the chemical processing of carbohydrates, fats, and proteins uses, a complex series or reactions known as the citric acid cycle (also known as the Krebs cycle). (There are other energy-producing processes, of course, such as photosynthesis.) The question to be answered is how this complex series of reactions first arose:

New Insights Into The Origin Of Life On Earth

In an advance toward understanding the origin of life on Earth, scientists have shown that parts of the Krebs cycle can run in reverse, producing biomolecules that could jump-start life with only sunlight and a mineral present in the primordial oceans.

The Krebs cycle is a series of chemical reactions of central importance in cells -- part of a metabolic pathway that changes carbohydrates, fats and proteins into carbon dioxide and water to generate energy.

Since the cycle can run backwards, it is possible to identify an inorganic compound that may have kickstarted the process:

Nature's Jump-Starter
Reporting in next week's Journal of the American Chemical Society, researchers at Harvard University say they may have found at least one of the original players. Called sphalerite, the compound is a mix of zinc and sulfur ejected from hydrothermal vents and known to have been plentiful in Earth's early seas. Geochemist and co-author Scot Martin says the team's new lab experiments show that when immersed in sterile water and exposed to sunlight, sphalerite can create three of the five basic organic chemicals necessary to start the Krebs cycle in relatively quick fashion. Further research is needed to isolate the other compound or compounds that could have produced the remaining two Krebs ingredients, he notes. If scientists can find their sources, then they will know that the five chemical foundations of the Krebs cycle were being manufactured easily and routinely in Earth's early oceans.

In addition to relatively simple organic chemical building blocks and chemical reactions that can release energy to make an organism that is "alive", there is a third prerequisite for life: some method of storing information about an organism's composition and structure so that the organism can replicate itself, instead of simply disappearing after each generation. In other words, genetic material.

Today, that genetic material consists of DNA and RNA, which in turn are made up of a handful of bases that act as symbols encoding the genetic message and are arranged along a linear backbone of simple sugar and phosphate groups. But are these the only possible chemical entities that can perform this kind of function?

In the past, other possibilities have been suggested, such as peptide nucleic acids (PNAs). A PNA has a backbone formed of simple molecules consisting of carbon, nitrogen, hydrogen, and oxygen. These are liked together by peptide bonds, which form when H- and OH- units from two molecules combine to form H2O, leaving the original molecules joined to each other. Such peptide bonds also form the backbone of proteins. But unlike proteins, PNAs have DNA-like bases attached to the backbone instead of amino acids. However, PNAs do not occur naturally, so they do not seem to have played a role in life on Earth.

If there are other ways of structuring a backbone, perhaps comparing them to what is actually used in RNA (the sugar known as ribose) and DNA (the sugar deoxyribose) would suggest why the latter proved to win out. That was the idea behind this research:

Uncovering DNA's 'Sweet' Secret
“These molecules are the result of evolution,” said Egli, professor of Biochemistry. “Somehow they have been shaped and optimized for a particular purpose.”

“For a chemist, it makes sense to analyze the origin of these molecules.”

One particular curiosity: how did DNA and RNA come to incorporate five-carbon sugars into their “backbone” when six-carbon sugars, like glucose, may have been more common? Egli has been searching for the answer to that question for the past 13 years.

Recently, Egli and colleagues solved a structure that divulges DNA's “sweet” secret. In a recent issue of the Journal of the American Chemical Society, Egli and colleagues report the X-ray crystal structure of homo-DNA, an artificial analog of DNA in which the usual five-carbon sugar has been replaced with a six-carbon sugar.

It was found that homo-DNA is more stable that DNA/RNA and it allows a wider variety of bases to be attached. So why didn't it prevail?
[D]espite homo-DNA's apparent versatility in base pairing and its thermodynamic stability, other features of the molecule's architecture probably preclude it from being a viable genetic system

For example, it cannot pair with other nucleic acids — unlike DNA and RNA which can and must pair with each other. Also the steep angle, or inclination, between the sugar backbone and the bases of homo-DNA requires that the pairing strands align strictly in an antiparallel fashion — unlike DNA which can adopt a parallel orientation. Finally, the irregular spaces between the “rungs” prevent homo-DNA from taking on the uniform structure DNA uses to store genetic information.

The findings suggest that fully hydroxylated six-carbon sugars probably would not have produced a stable base-pairing system capable of carrying genetic information as efficiently as DNA.

So that variation didn't work out. But what about the possibility of using a different set of bases than the purines and pyrimidines which actually occur? That was investigated in this study:

Origin Of Life: The Search For The First Genetic Material
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.

The conclusion was that the critical factor affecting the composition of modern genetic material was the structure of the bases rather than the structure of the backbone. It was necessary to have only certain bases which are capable of pairing up in specific ways, as occurs in double-stranded DNA and DNA-RNA combinations.

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