{"566311":{"#nid":"566311","#data":{"type":"news","title":"Looking for the Origin of Life Inside a 4 Billion-Old Molecular Machine","body":[{"value":"\u003Cp\u003EHow did life on Earth originate from simple molecules? This question is one of the deepest, most fundamental questions of science, and it remains unanswered.\u003C\/p\u003E\u003Cp\u003EIn Georgia Tech\u2019s College of Sciences, scientists are trying to decipher the origin of life. Among them is \u003Ca href=\u0022http:\/\/www.chemistry.gatech.edu\/faculty\/williams\/\u0022\u003ELoren D. Williams\u003C\/a\u003E, a professor in the \u003Ca href=\u0022http:\/\/www.chemistry.gatech.edu\/\u0022\u003ESchool of Chemistry and Biochemistry\u003C\/a\u003E and a member of the \u003Ca href=\u0022http:\/\/www.ibb.gatech.edu\/\u0022\u003EParker H. Petit Institute of Bioengineering and Biosciences.\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EFor Williams, part of the answer has to come from the ribosome. This gigantic molecular machine comprising ribonucleic acids (RNA) and proteins enables a key distinction of life:\u0026nbsp; translation of genetic information to proteins.\u003C\/p\u003E\u003Cp\u003EHow did translation begin? Work in Williams\u0027 lab suggests that \u003Ca href=\u0022http:\/\/www.pnas.org\/content\/112\/50\/15396.abstract\u0022\u003Etranslation is the product of molecular symbiosis, that ancestors of RNA and protein were molecular symbionts, and that life arose from the coevolution of proteins and RNA\u003C\/a\u003E. That startling notion \u003Ca href=\u0022http:\/\/link.springer.com\/article\/10.1007\/s00239-015-9669-9\u0022\u003Echallenges the popular \u201cRNA world\u201d hypothesis of the origin of life\u003C\/a\u003E. That world posits a time when life was based only on RNA, RNA-catalyzed transformations, and RNA-based genetic material; proteins, the ribosome, and translation appeared later.\u003C\/p\u003E\u003Cp\u003EAt the meeting of the American Chemical Society in Philadelphia, Williams makes the case that the early history of the ribosome is also the history of the origin of life.\u003C\/p\u003E\u003Cp\u003EWilliams and his coworkers base their conclusions on meticulous analysis of the \u201cfossil record\u201d in all ribosomes. As trees imprint events in their rings, or ice cores suspend time by preserving matter in frozen columns, ribosomes are time machines, Williams says, one \u201cthat allows us to look at the behaviors of ancient molecules 3.8 billion years ago.\u201d\u003C\/p\u003E\u003Cp\u003ECrystal structures indicate that the modern ribosome grew by accretion, Williams says. By peeling away the layers deposited in the ribosome over almost 4 billion years, Williams and coworkers reached inside the so-called common core, which is the common denominator and oldest part of biology. Deep inside is the peptidyl transferase center, which links amino acids through peptide bonds \u201cThis part of the ribosome originates in chemistry,\u201d Williams says. \u201cIt is pre-biology.\u201d\u003C\/p\u003E\u003Cp\u003EIf two amino acids are located within the peptidyl transferase center, they will easily form a peptide bond. \u201cBut as soon as you do that in the absence of the ribosome, the ends of the amino acids come together, forming a cyclic structure,\u201d Williams says. Polymers cannot form. But if the ends are kept apart, by the primitive ribosome, a chain of peptide bonds could grow into a polymer.\u003C\/p\u003E\u003Cp\u003EAs it happens, a feature of the ancient ribosome is a hole in the middle, foreshadowing the tunnel through which proteins leave modern ribosomes after they are made.\u0026nbsp; \u201cWe think that an original function of the ribosome was not to catalyze peptide bond formation but to keep amino acids from forming cyclic structures and thereby form longer peptides,\u201d Williams says.\u003C\/p\u003E\u003Cp\u003EThe tunnel through which all proteins pass is a constant in the evolution of the ribosome. By examining crystal structures and mapping how modern ribosomes grew from the common core, Williams gleaned that ribosomes evolved to make this tunnel long and rigid.\u003C\/p\u003E\u003Cp\u003EWhy? Williams suggests that without a long tunnel, a synthesized protein would fold at once, become active, and start eating the ribosome\u2019s structure. \u201cThe tunnel is saying to the protein, no you cannot become functional yet.\u201d\u003C\/p\u003E\u003Cp\u003ERibosome crystal structures suggest something else: When early ribosomes made small peptides that were not capable of folding, some of these peptides stuck to and accreted on the ribosome. \u201cWe think the ribosome started making peptides in the first place to give itself greater stability,\u201d Williams says. In making peptides that became bound to the ribosome like scaffolding, the ribosome became bigger and more stable.\u003C\/p\u003E\u003Cp\u003EAs evidence, Williams presents the protein fossils in ribosomes. The oldest ones are frozen random coils \u201cThat\u2019s the first thing we think the ribosome made. They got stuck, they didn\u2019t fold. They don\u2019t look like modern proteins.\u201d\u003C\/p\u003E\u003Cp\u003ENext are isolated beta hairpins. \u201cNowhere else in biology will you see isolated beta hairpins without other protein around it,\u201d Williams notes. \u201cOnly in the core of the ribosome do you see beta hairpins surrounded by RNA.\u201d These isolated beta hairpins are the most ancient folded proteins in biology, he says.\u003C\/p\u003E\u003Cp\u003EThen come more modern proteins, made of beta sheets and alpha helices, with hydrophobic exteriors and hydrophilic interiors and the ability to fold to globular forms.\u003C\/p\u003E\u003Cp\u003E\u201cOur results show that protein folding from random-coil peptides to functional polymeric domains was an emergent property of the interactions of ribosomal RNA and peptides,\u201d Williams says. \u201cThe ribosome is the cradle of protein evolution.\u201d\u003C\/p\u003E\u003Cp\u003EAlong with \u003Ca href=\u0022https:\/\/ww2.chemistry.gatech.edu\/hud\/prof-nicholas-v-hud\u0022\u003ENicholas V. Hud\u003C\/a\u003E, a professor at the School of Chemistry and Biochemistry and the director of the \u003Ca href=\u0022http:\/\/centerforchemicalevolution.com\/\u0022\u003ECenter for Chemical Evolution\u003C\/a\u003E, Williams and other origin-of-life researchers in Georgia Tech propose that chemical evolution\u2014driven by assembly and other processes that increase stability\u2014gradually converted to biological evolution, involving genes, enzymes, and ribosomes.\u003C\/p\u003E\u003Cp\u003E\u201cWe believe that chemical evolution was driven by assembly,\u201d Williams says. \u201cIn biology, things that are assembled live longer chemically than those that are not. A folded protein is chemically stable. Unfold it, and it falls apart.\u201d So it was in chemical evolution. Things that could assemble existed longer than those that couldn\u2019t.\u003C\/p\u003E\u003Cp\u003E\u201cIf you had a molecule that could assemble and make peptides that bound to it, and they co-assemble, all of a sudden you have something better,\u201d Williams says. \u201cWe think the reason proteins came into biology was that they stabilized the ribosome and protected it from degradation. The ribosome was looking out for itself. It was an evolutionary process by the ribosome, for the ribosome, and of the ribosome.\u003C\/p\u003E\u003Cp\u003E\u201cWe have the historical record or molecules. These things are preserved in the ribosome, we can see them. There is a molecular record of the origin of life.\u201d\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EFigure Caption\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThe evolution of the ribosome, illustrating growth of the large (LSU) and small (SSU) subunits, first as separate units and eventually as parts of a whole.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EIn Phase 1, ancestral RNAs form stem loops and minihelices. In Phase 2, LSU, which has a short tunnel, condenses short, nonspecific, peptide-like oligomers. Some of these oligomers bind back onto the ribosome and stabilize it. At this point, SSU may have a single-stranded RNA-binding function. In Phase 3, the subunits associate, mediated by the expansion of tRNA from a minihelix to its modern L-shape. The tunnel elongates. In Phase 4, the two subunits associate and they evolve together. The ribosome is a noncoding diffusive ribozyme in which proto-mRNA and the SSU act as positioning cofactors, producing peptide-like oligomers, some of which form beta-hairpins. In Phase 5, the ribosome expands to an energy-driven, translocating, decoding machine. Phase 6 marks completion of the common core with a proteinized surface (the proteins are omitted for clarity). mRNA is shown in light green. The A-site tRNA is magenta, the P-site tRNA is cyan, and the E-site tRNA is dark green.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EAdapted from \u003Ca href=\u0022http:\/\/www.pnas.org\/content\/112\/50\/15396.abstract\u0022\u003EA. S. Petrov et al., 2015, \u003C\/a\u003E\u003C\/em\u003E\u003Ca href=\u0022http:\/\/www.pnas.org\/content\/112\/50\/15396.abstract\u0022\u003EProc. Natl. Acad. Sci. U.S.A\u003C\/a\u003E\u003Cem\u003E\u003Ca href=\u0022http:\/\/www.pnas.org\/content\/112\/50\/15396.abstract\u0022\u003E. 112:15396\u201315401\u003C\/a\u003E. Courtesy of Loren Williams.\u003C\/em\u003E\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Crystal structures of the ribosome suggest coevolution of RNA and proteins."}],"field_summary":[{"value":"\u003Cp\u003ECrystal structures of the ribosome suggest coevolution of RNA and proteins.\u0026nbsp;\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Crystal structures of the ribosome suggest coevolution of RNA and proteins."}],"uid":"30678","created_gmt":"2016-08-22 15:49:23","changed_gmt":"2016-10-08 03:22:23","author":"A. Maureen Rouhi","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-08-24T00:00:00-04:00","iso_date":"2016-08-24T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"565061":{"id":"565061","type":"image","title":"The evolution of the ribosome, illustrating growth of the large (LSU) and small (SSU) subunits, separately at first and eventually as parts of a whole","body":null,"created":"1471538831","gmt_created":"2016-08-18 16:47:11","changed":"1475895369","gmt_changed":"2016-10-08 02:56:09","alt":"The evolution of the ribosome, illustrating growth of the large (LSU) and small (SSU) subunits, separately at first and eventually as parts of a whole","file":{"fid":"206888","name":"ribosomeevolution.loren_.williams.jpg","image_path":"\/sites\/default\/files\/images\/ribosomeevolution.loren_.williams.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/ribosomeevolution.loren_.williams.jpg","mime":"image\/jpeg","size":722545,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ribosomeevolution.loren_.williams.jpg?itok=vuJcU8Xe"}},"566321":{"id":"566321","type":"image","title":"Loren Williams","body":null,"created":"1471895463","gmt_created":"2016-08-22 19:51:03","changed":"1475895371","gmt_changed":"2016-10-08 02:56:11","alt":"Loren Williams","file":{"fid":"206920","name":"acs_fall_loren_williams.headshot.jpg","image_path":"\/sites\/default\/files\/images\/acs_fall_loren_williams.headshot.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/acs_fall_loren_williams.headshot.jpg","mime":"image\/jpeg","size":96201,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/acs_fall_loren_williams.headshot.jpg?itok=KdNfrYPw"}},"566331":{"id":"566331","type":"image","title":"RNA-protein coevolution","body":null,"created":"1471895702","gmt_created":"2016-08-22 19:55:02","changed":"1475895371","gmt_changed":"2016-10-08 02:56:11","alt":"RNA-protein coevolution","file":{"fid":"206921","name":"ribosome.protein.coevolution.png","image_path":"\/sites\/default\/files\/images\/ribosome.protein.coevolution.png","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/ribosome.protein.coevolution.png","mime":"image\/png","size":34225,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/ribosome.protein.coevolution.png?itok=z4v9Js_a"}}},"media_ids":["565061","566321","566331"],"groups":[{"id":"1278","name":"College of Sciences"}],"categories":[{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"4896","name":"College of Sciences"},{"id":"10720","name":"Loren Williams"},{"id":"4504","name":"Nicholas Hud"},{"id":"9854","name":"Origin Of Life"},{"id":"11625","name":"ribosomes"},{"id":"166928","name":"School of Chemistry and Biochemistry"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[],"email":[],"slides":[],"orientation":[],"userdata":""}}}