Thursday, December 15, 2005

Jump-Starting a Cellular World: Investigating the Origin of Life, from Soup to Networks

The Public Library of Science has a large number of papers online, freely available. Here's an interesting one...

Beginning with a single cell, Darwinian evolution provides a simple, robust, and powerful algorithm for deriving all the astonishing richness of life, from bacteria to brains. Natural selection and other evolutionary forces, acting on surplus populations of replicating cells and multicellular organisms, lead inevitably to evolution and adaptation. Give biologists a cell, and they’ll give you the world. But beyond assuming the fi rst cell must have somehow come into existence, how do biologists explain its emergence from the prebiotic world four billion years ago?

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In the early 1980s, just as Miller-type chemistry was falling out of favor, RNA emerged as the rising star of origin-of life research, based on a startling discovery. Up to this point, evolution appeared to have a severe chicken-and-egg problem: information-bearing DNA codes for protein, but catalytic proteins are essential to make DNA. That the two could have arisen independently but still work in concert seemed highly unlikely. But RNA, which was well-known in its role as temporary information carrier, also turned out to be catalytic. Indeed, a host of functions in modern cells that were once thought to be the province of proteins are instead supervised by catalytic RNA.
Despite years of experiments with dozens of different strategies, no one has figured out how to make this most essential of starting ingredients for an RNA world. “There is a growing realization that we may need to look beyond RNA,” Szostak says, to molecules whose chemistry is a bit more tractable, such as a peptide nucleic acid (PNA), a synthetic amino acid–nucleotide hybrid. These original replicators might then have given way to RNA, says Leslie Orgel, senior fellow and research professor at the Salk Institute of Biological Studies. The case for PNA is weak, though.
The possibility that metabolism first began at hydrothermal vents has been advanced most recently by Michael Russell, Research Professor of Geology at the Scottish Universities Environmental Research Centre in Glasgow, and William Martin, Professor at the University of Düsseldorf. Russell and Martin propose that life’s metabolism developed not on a two-dimensional pyrite surface but within tiny cavities lined with iron monosulfi de, through which percolated an energy-rich mix of hydrogen and carbon dioxide dissolved in seawater.
The slow trickle of hydrogen and carbon dioxide through such chambers and across the iron sulfide catalyst promotes formation of acetate, according to Russell and Martin. Acetate is a key intermediate in virtually all biosynthetic pathways, and in modern cells, enters these reactions tethered to sulfur. In modern bacteria, the two enzymes that make acetate depend on a catalytic core of iron, nickel, and sulfur, arranged almost exactly as they are in the free mineral itself. “In other words,” Russell and Martin have written, these enzymatic metal clusters “are not inventions of the biological world, rather they are mimics of minerals that are indisputably older, and which themselves have catalytic activity in the absence of protein”
Russell and Martin’s model also provides a solution to another thorny issue in jump-starting life, that of concentration. An essential feature of all cells is their ability to maintain high concentrations of materials that are in short supply in the world around them. In the absence of a cell membrane, how did proto-life forms collect raw materials, and prevent products from dissipating into the vastness of the environment around them? Russell’s chambers solve this problem in essentially the same way modern cells do, with an external boundary that is permeable to small reactant molecules, but much less so to larger product ones.
...the most exciting development in the metabolism-first camp, “the really new idea,” is that small organic molecules, such as amino acids, can catalyze the formation of other small organic molecules, such as nucleic acids. “This has emerged only in the last two years,” he says. This view has found strong support from a new finding published in the journal Chemistry in August 2005, which indicates that single amino acids can catalyze the creation of sugars from simple starting materials with enzyme-like specificity. “What has emerged is a very strong self-organizing principle,” says Morowitz. In this view, while iron sulfide may have been the original catalyst, it did not remain the only one for long. As products of the original reactions catalyzed new reactions, metabolic networks quickly arose. Feedback loops developed when two molecules regulated one another’s
It is still unclear how, or whether, these competing models will fit together, and whether they will lead to a robust scenario for life’s origin. Indeed, all may eventually prove wrong, and the real solution may lie hidden in some discovery yet to be made. Whatever the difficulties, says Morowitz, the allure of the field lies in its potential to answer the biggest question of them all. “You’re not going to make drugs or better agriculture. You’re going to make a philosophical impact.” Szostak agrees: “These are the big questions. Anybody who thinks has to be grabbed by these.”

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