April 10, 2006

Less Tar, More Life

Constraining Scenarios for the Origin of Life: Working Backwards, Working Forwards, and Synthesizing Life in the Laboratory
Steven Benner, University of Florida
27 min. (slideshow requires QCShow Player)
Audio only (mp3 format)
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Sugars are the literal backbone of life on this planet. In particular, one rare form of sugar, ribose, is the structural spine of RNA and DNA.

Evidence for an "RNA world," an hypothesized episode of the earliest form of life on Earth during which RNA was the only genetically encoded component of biological catalysts, is found in the ribosome, in catalytic RNA molecules, and in contemporary metabolisms. The existence of this RNA world assumes a large prebiotic source of ribose or other similar sugars.

Nonetheless, for all of its importance, the fact that RNA could form spontaneously and persist under prebiotic conditions has been seriously doubted.

In 1953, Stanley Miller demonstrated that electric sparks in a primitive atmosphere made amino acids, the building blocks of proteins. Miller's experiment however failed to identify sugars that were needed for genetic material. Steven Benner, this week's lecturer, has said, "The sugar ribose can be formed from interstellar precursors under prebiotic conditions, but ribose is too unstable to survive under Miller's conditions." It turns into tar if not handled very carefully.

Miller's discouragement, after 40 years of experiments in trying to synthesize ribose prebiotically, was such that it caused him to write in 1995, "The first genetic material could not have contained ribose or other sugars because of their instability."

In contrast, Benner offers in this talk a very simple mechanism to allow the prebiotic formation and persistence of ribose. The presence of boron, which is derived from borate minerals, allows ribose and other sugars to remain stable for days.

Borates are not rare on planetary surfaces. Borate is incompatible with many silicate minerals, and because of that incompatability is concentrated in residual melts during rock formation, and frequently appears in igneous rocks as tourmalines. Weathering produces soluble borate salts, which often appear as alkaline evaporites. They are known in Death Valley, and they appear as crusts on outcrops in Antarctic dry valleys, and are likely on the surface of Mars as well.

While Benner is not claiming that this is the precise path that the initial evolution of life on this planet took, it makes its likelihood enormously more plausible and all the more simple.

In the second half of the talk, Benner changes gears and speaks to the subject of the artificial synthesis of life in the laboratory. At the core of all life on Earth lies an alphabet of five bases, A, G, C, T and U. These are the base pairs that interlock the ribose spine in the information-bearing molecules, RNA and DNA.

Benner notes that there is no reason to suspect that these five bases were the only bases used in the earliest forms of life. He outlines eight more bases that fit the necessary Watson-Crick geometry and presents a logical argument that these other bases — or something very much like them — quite likely existed in the first forms of RNA on Earth.

— Wirt Atmar

About the Speaker

Steven Benner is a University of Florida distinguished professor of chemistry, anatomy and cell biology and is a member of NASA's Astrobiology Institute.

The Benner laboratory at the University of Florida is an originator of the field of "synthetic biology", which seeks to generate, by chemical synthesis, molecules that reproduce the complex behavior of living systems, including their genetics, inheritance, and evolution. Some high points of past work in chemical genetics are listed below:

• Gene synthesis. In 1984, the Benner laboratory was the first to report the chemical synthesis of a gene encoding an enzyme, following Khorana's synthesis of a shorter gene for tRNA in 1970. This was the first designed gene of any kind, and the design strategies introduced in this synthesis are now widely used to support protein engineering.

• Artificial genetic systems. The Benner laboratory introduced the first expanded DNA alphabets in 1989, and developed these into an Artificially Expanded Genetic Information System (AEGIS), which now has its own supporting molecular biology. AEGIS enables the synthesis of proteins with more than 20 encoded amino acids, and provides insight into how nucleic acids form duplex structures, how proteins interact with nucleic acids, and how alternative genetic systems might appear in non-terrean life.

• A "second generation" model for nucleic acids. The first generation model for nucleic acid structure, proposed by Watson and Crick 50 years ago, has proven inadequate to guide modification of the core structure of DNA. The Benner group has used synthetic organic chemistry and biophysics to create a "second generation" model for nucleic acid structure. The model emphasizes the role of the sugar and phosphate backbone in the genetic molecular recognition event, and creates perspectives on how nucleic acids work, tools for diagnostics and nanotechnology, and insights on how extraterrestrial life might be recognized.

• Practical genotyping tools. The FDA has approved two products that use AEGIS in human diagnostics. These monitor the loads of virus in patients infected with hepatitis C and HIV. AEGIS also enables products developed by EraGen Biosciences for multiplexed detection of genetic markers and single nucleotide polymorphisms in patient samples. These tools will allow personalized medicine using "point-of-care" genetic analysis, as well as research tools that measure the level of individual mRNA molecules within single processes of single living neurons.

• Astrobiology. The exploration of planets other than Earth seeks signs of non-terrean life. The Benner group has worked to identify molecular structures likely to be universal features of living systems regardless of their genesis, and not likely products of non-biological processes. These are "bio-signatures", both for terrean-like life and for "weird" life forms. As a member of the NASA Astrobiology Institute (with the Univeristy of Washington), and in collaborations with the Jet Propulsion Laboratory and the University of Michigan, the Benner group is designing the next generation of probes to Mars.