Self-Assembling Molecules Like These May Have Sparked Life on Earth; For Nicholas Hud, a chemist at the Georgia Institute of Technology, the turning point came in July of 2012 when two of his students rushed into his office with a tiny tube of gel. The contents, which looked like a blob of lemon Jell-O, represented the fruits of a 20-year effort to construct something that looked like life from the cacophony of chemicals that were available on the early Earth. To some biochemists, Hud’s attempts to find an evolutionary precursor to ribonucleic acid may have seemed a fool’s errand. The dominant theory to explain the origins of life — known as the RNA world hypothesis — regards ribonucleic acid as the first biological molecule. Its allure comes from the molecule’s dual nature. Unlike DNA, the molecule that provides the blueprint for all living things, RNA acts as both an information carrier and an enzyme, catalyzing reactions. That means the molecule has the potential to copy itself and to pass along its genetic code, two essential components for Darwinian evolution. If RNA was indeed the first biological molecule, discovering how it first formed would illuminate the birth of life. The basic building blocks of RNA were available on prebiotic Earth, but chemists, including Hud, have spent years trying to assemble them into an RNA molecule with little success. About 15 years ago, Hud grew frustrated with that search and decided to explore an alternative idea: Perhaps the first biological molecule was not RNA, but a precursor that possessed similar characteristics and could more easily assemble itself from prebiotic ingredients. Perhaps RNA evolved from this more ancient molecule, just as DNA evolved from RNA. Hud’s team started exploring this idea explicitly a decade ago. When the gel formed in 2012, after the testing of dozens of chemicals, Hud’s team knew it had made a significant advance in the chemistry of a possible proto-RNA world. After years of failed attempts, a surprisingly simple chemical recipe had produced a conglomerate of long, ribbonlike molecules whose structure and chemical components resembled those of RNA. Hud immediately asked the students to recite the protocol they had used for the reaction, scribbling it down as they spoke. “I wanted to be sure that we would always remember how they had obtained [the end-product] by such a simple procedure,” he said. In December 2013, the results were published in the Journal of the American Chemical Society. “In my opinion, nothing like this has been seen before,” said Stephen Freeland, a biologist at the University of Maryland Baltimore County, who was not involved in the study. Although he isn’t certain that the chemicals Hud picked will end up being the precise components of proto-RNA, Freeland said Hud has “made conceptual progress.” Hud isn’t the first scientist to explore an alternative chemistry for RNA. But the robustness of his reaction is unique — the molecules seem to seek one another out, reacting without a lot of chemical coaxing. Hud and others say this ease of creation is essential for reactions to have taken place in the chaotic chemical cauldron of early Earth. “Before this, people just didn’t focus on the real-world situation,” Freeland said. “We need something so robust that no matter what the situation is, it will still happen.” Hud’s team is now testing whether its reactions will work in a messy mix of molecules more analogous to the primordial soup. Hud’s chemistry — and the concept of proto-RNA in general — still faces hurdles. His molecule possesses a polymer-like structure of repeating units similar to nucleic acids. In RNA and DNA, the sequence of those units is essential for carrying information, allowing those molecules to store and transmit the code of life. But Hud’s molecule uses only two chemical letters, compared with RNA’s four, and the repeating units can easily come apart. That means it doesn’t have the informational content of RNA, an essential characteristic of life. Proponents of the traditional RNA world hypothesis say that moving from an RNA precursor like Hud’s to RNA itself still represents an incredible challenge, possibly as daunting as making RNA from scratch. If these molecules were successful enough to launch the origins of life, where are they now? “To me, the proto-RNA idea raises more questions than it answers,” said John Sutherland, a chemist at the MRC Laboratory of Molecular Biology in Cambridge, England, who nonetheless described Hud’s work as elegant and well done. “If it’s too difficult for RNA to assemble chemically, how can a primitive biology invent RNA?” Photo: Self-Assembling Molecules Like These May Have Sparked Life on Earth; For Nicholas Hud, a chemist at the Georgia Institute of Technology, the turning point came in July of 2012 when two of his students rushed into his office with a tiny tube of gel. The contents, which looked like a blob of lemon Jell-O, represented the fruits of a 20-year effort to construct something that looked like life from the cacophony of chemicals that were available on the early Earth. To some biochemists, Hud’s attempts to find an evolutionary precursor to ribonucleic acid may have seemed a fool’s errand. The dominant theory to explain the origins of life — known as the RNA world hypothesis — regards ribonucleic acid as the first biological molecule. Its allure comes from the molecule’s dual nature. Unlike DNA, the molecule that provides the blueprint for all living things, RNA acts as both an information carrier and an enzyme, catalyzing reactions. That means the molecule has the potential to copy itself and to pass along its genetic code, two essential components for Darwinian evolution. If RNA was indeed the first biological molecule, discovering how it first formed would illuminate the birth of life. The basic building blocks of RNA were available on prebiotic Earth, but chemists, including Hud, have spent years trying to assemble them into an RNA molecule with little success. About 15 years ago, Hud grew frustrated with that search and decided to explore an alternative idea: Perhaps the first biological molecule was not RNA, but a precursor that possessed similar characteristics and could more easily assemble itself from prebiotic ingredients. Perhaps RNA evolved from this more ancient molecule, just as DNA evolved from RNA. Hud’s team started exploring this idea explicitly a decade ago. When the gel formed in 2012, after the testing of dozens of chemicals, Hud’s team knew it had made a significant advance in the chemistry of a possible proto-RNA world. After years of failed attempts, a surprisingly simple chemical recipe had produced a conglomerate of long, ribbonlike molecules whose structure and chemical components resembled those of RNA. Hud immediately asked the students to recite the protocol they had used for the reaction, scribbling it down as they spoke. “I wanted to be sure that we would always remember how they had obtained [the end-product] by such a simple procedure,” he said. In December 2013, the results were published in the Journal of the American Chemical Society. “In my opinion, nothing like this has been seen before,” said Stephen Freeland, a biologist at the University of Maryland Baltimore County, who was not involved in the study. Although he isn’t certain that the chemicals Hud picked will end up being the precise components of proto-RNA, Freeland said Hud has “made conceptual progress.” Hud isn’t the first scientist to explore an alternative chemistry for RNA. But the robustness of his reaction is unique — the molecules seem to seek one another out, reacting without a lot of chemical coaxing. Hud and others say this ease of creation is essential for reactions to have taken place in the chaotic chemical cauldron of early Earth. “Before this, people just didn’t focus on the real-world situation,” Freeland said. “We need something so robust that no matter what the situation is, it will still happen.” Hud’s team is now testing whether its reactions will work in a messy mix of molecules more analogous to the primordial soup. Hud’s chemistry — and the concept of proto-RNA in general — still faces hurdles. His molecule possesses a polymer-like structure of repeating units similar to nucleic acids. In RNA and DNA, the sequence of those units is essential for carrying information, allowing those molecules to store and transmit the code of life. But Hud’s molecule uses only two chemical letters, compared with RNA’s four, and the repeating units can easily come apart. That means it doesn’t have the informational content of RNA, an essential characteristic of life. Proponents of the traditional RNA world hypothesis say that moving from an RNA precursor like Hud’s to RNA itself still represents an incredible challenge, possibly as daunting as making RNA from scratch. If these molecules were successful enough to launch the origins of life, where are they now? “To me, the proto-RNA idea raises more questions than it answers,” said John Sutherland, a chemist at the MRC Laboratory of Molecular Biology in Cambridge, England, who nonetheless described Hud’s work as elegant and well done. “If it’s too difficult for RNA to assemble chemically, how can a primitive biology invent RNA?”
Posted on: Tue, 11 Feb 2014 15:09:33 +0000
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