{"684992":{"#nid":"684992","#data":{"type":"news","title":"Molecular \u2018Fossils\u2019 Offer Microscopic Clues to the Origins of Life \u2013 But They Take Care to\u00a0Interpret","body":[{"value":"\u003Cp\u003EThe questions of how humankind came to be, and whether we are alone in the universe, have \u003Ca href=\u0022https:\/\/doi.org\/10.1017\/S1473550407003692\u0022\u003Ecaptured imaginations for millennia\u003C\/a\u003E. But to answer these questions, scientists must first understand life itself and how it could have arisen.\u003C\/p\u003E\u003Cp\u003EIn our work as \u003Ca href=\u0022https:\/\/scholar.google.com\/citations?user=0SOG_SsAAAAJ\u0026amp;hl=vi\u0022\u003Eevolutionary biochemists\u003C\/a\u003E and \u003Ca href=\u0022https:\/\/scholar.google.com\/citations?user=e_IKMz4AAAAJ\u0026amp;hl=en\u0022\u003Eprotein historians\u003C\/a\u003E, these core questions form the foundation of our research programs. To study life\u2019s history billions of years ago, we often use clues called \u003Ca href=\u0022https:\/\/doi.org\/10.1038\/embor.2013.162\u0022\u003Emolecular \u201cfossils\u201d\u003C\/a\u003E \u2013 ancient structures shared by all living organisms.\u003C\/p\u003E\u003Cp\u003ERecently, we discovered that an important molecular fossil found in an ancient protein family \u003Ca href=\u0022https:\/\/doi.org\/10.1093\/molbev\/msaf055\u0022\u003Emay not be what it seems\u003C\/a\u003E. The dilemma centers, in part, on a simple question: What does it mean if a simple molecular structure \u2013 the fossil \u2013 is found in every single organism on Earth? Do molecular fossils point to the seeds that gave rise to modern biological complexity, or are they simply the stubborn pieces that have resisted erosion over time? The answers have far-reaching implications for how scientists understand the origins of biology.\u003C\/p\u003E\u003Ch2\u003EFollow the Phosphorus to Follow Life\u003C\/h2\u003E\u003Cp\u003ELife is made of many different building blocks, one of the most important of which is the \u003Ca href=\u0022https:\/\/www.smithsonianmag.com\/air-space-magazine\/phosporus-you-cant-have-life-without-it-least-earth-180967243\/\u0022\u003Echemical element phosphorus\u003C\/a\u003E. Phosphorus makes up part of your genetic material, powers complex metabolic reactions and acts as a molecular switch to control enzymes.\u003C\/p\u003E\u003Cp\u003EPhosphorus compounds \u2013 specifically a charged form called phosphate \u2013 have a number of unique chemical properties that other biological compounds cannot match. In the words of the pioneering organic chemist F.H. Westheimer, they are chemically able to \u201c\u003Ca href=\u0022https:\/\/doi.org\/10.1126\/science.2434996\u0022\u003Edo almost everything\u003C\/a\u003E.\u201d\u003C\/p\u003E\u003Cp\u003ETheir unique combination of stability, versatility and adaptability is why many researchers argue that \u003Ca href=\u0022https:\/\/www.popularmechanics.com\/space\/solar-system\/a19685943\/alien-life-phosphorus\/\u0022\u003Efollowing phosphorus is key to finding life\u003C\/a\u003E. The presence of phosphorus both close to home \u2013 in the ocean or on one of Saturn\u2019s moons \u2013 and in the farthest reaches of our galaxy is strong evidence for the potential for life beyond Earth.\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/images.theconversation.com\/files\/690272\/original\/file-20250910-56-jjsn6y.jpg?ixlib=rb-4.1.0\u0026amp;q=45\u0026amp;auto=format\u0026amp;w=1000\u0026amp;fit=clip\u0022\u003E\u003Cimg src=\u0022https:\/\/images.theconversation.com\/files\/690272\/original\/file-20250910-56-jjsn6y.jpg?ixlib=rb-4.1.0\u0026amp;q=45\u0026amp;auto=format\u0026amp;w=754\u0026amp;fit=clip\u0022 alt=\u0022Chemical structure of a nucleotide, made of a phosphate, ribose sugar and base\u0022\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EPhosphate is part of many essential biological molecules, including the building blocks of DNA. \u003Ca href=\u0022https:\/\/opentextbc.ca\/biology\/chapter\/9-1-the-structure-of-dna\/\u0022\u003ECharles Molnar and Jane Gair\u003C\/a\u003E, \u003Ca href=\u0022http:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/\u0022\u003ECC BY-SA\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EIf phosphorus is so critical to life, how did early biology \u003Ca href=\u0022https:\/\/evolution.berkeley.edu\/from-soup-to-cells-the-origin-of-life\/how-did-life-originate\/\u0022\u003Epredating cells\u003C\/a\u003E first use it?\u003C\/p\u003E\u003Cp\u003EToday, biological organisms are able to make use of phosphates \u003Ca href=\u0022https:\/\/theconversation.com\/what-is-a-protein-a-biologist-explains-152870\u0022\u003Ethrough proteins\u003C\/a\u003E \u2013 molecular machines that regulate all aspects of life. By \u003Ca href=\u0022https:\/\/doi.org\/10.1039\/B9NJ00718K\u0022\u003Ebinding to proteins, phosphates\u003C\/a\u003E regulate metabolism and cellular communication, and they serve as a source of cellular energy.\u003C\/p\u003E\u003Cp\u003EFurther, the process of phosphorylation, or adding a phosphate group to a protein, is ubiquitous in biology and \u003Ca href=\u0022https:\/\/doi.org\/10.1098\/rstb.2012.0013\u0022\u003Eallows proteins to perform functions\u003C\/a\u003E their individual building blocks cannot. Without proteins, the existence of organisms such as bacteria and humans may not be possible.\u003C\/p\u003E\u003Cp\u003EGiven how essential phosphorus is to life, scientists hypothesize that phosphate binding was among the first biological functions to emerge on Earth. In fact, current evidence suggests that the \u003Ca href=\u0022https:\/\/doi.org\/10.7554\/eLife.64415\u0022\u003Efirst phosphate-binding proteins are truly ancient\u003C\/a\u003E \u2013 even older than the last universal common ancestor, the hypothetical mother cell to all life on Earth that \u003Ca href=\u0022https:\/\/doi.org\/10.1371\/journal.pgen.1007518\u0022\u003Eexisted around 4 billion years ago\u003C\/a\u003E.\u003C\/p\u003E\u003Ch2\u003EA Mysterious Phosphate-Binding Fossil\u003C\/h2\u003E\u003Cp\u003EOne family of phosphate-binding proteins, called \u003Ca href=\u0022https:\/\/doi.org\/10.1073\/pnas.1812400115\u0022\u003EP-loop NTPases\u003C\/a\u003E, regulates everything from the communication between cells to the storage of energy and are found across the tree of life. Because P-loop NTPases are among the most ancient protein families, analyzing their properties can provide key insights into both the emergence of proteins and how primitive life used phosphates.\u003C\/p\u003E\u003Cp\u003EAlthough P-loop NTPases are diverse in structure, they share a common motif called a P-loop. This component binds to phosphate by wrapping a nest of amino acids \u2013 the building blocks that make up proteins \u2013 around the molecule. \u003Ca href=\u0022https:\/\/doi.org\/10.7554\/eLife.64415\u0022\u003EEvery known organism\u003C\/a\u003E has multiple families of P-loop NTPase, which makes the P-loop an excellent example of a molecular fossil that can provide clues about the evolution of life. Our crude analysis of the human genome estimates that humans have about 5,000 copies of P-loops.\u003C\/p\u003E\u003Cp\u003EWhen part of a larger protein structure, the P-loop folds like origami into a shape that is ideal for \u003Ca href=\u0022https:\/\/doi.org\/10.1073\/pnas.1812400115\u0022\u003Ehugging a phosphate molecule\u003C\/a\u003E. These nests are extremely similar to each other, even when the surrounding proteins are only distantly related in function. A landmark study in 2012 argued that even if the P-loop nest is extracted from a protein, it can \u003Ca href=\u0022https:\/\/doi.org\/10.1002\/prot.24038\u0022\u003Estill bind to phosphate\u003C\/a\u003E. In other words, the ability of a P-loop to form a nest is determined by its interactions with phosphate, not its protein scaffold.\u003C\/p\u003E\u003Cp\u003EThis study provided the first evidence that some forms of the P-loop sequence could have functioned billions of years ago, even before the emergence of large, complex proteins. If true, this implies that P-loop nests may have seeded the emergence and evolution of many of the phosphate-binding proteins seen today.\u003C\/p\u003E\u003Ch2\u003EInterrogating the History of the P-loop\u003C\/h2\u003E\u003Cp\u003EThe pioneer of bioinformatics, Margaret Oakley Dayhoff, hypothesized in 1966 that the large collection of big proteins seen today \u003Ca href=\u0022https:\/\/doi.org\/10.1002\/anie.201609977\u0022\u003Earose from small peptides\u003C\/a\u003E that were duplicated and fused over long periods of time. Although P-loops may have evolved in a different way, Dayhoff\u2019s realization was the first to clarify how complex forms could have arisen from much simpler ones.\u003C\/p\u003E\u003Cp\u003EInspired by Dayhoff\u2019s hypothesis, we sought to interrogate the role that simple P-loops may have played in the evolution of the complex proteins key to life. Our findings challenge what\u2019s currently known about these molecular fossils.\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/images.theconversation.com\/files\/690273\/original\/file-20250910-56-q9xtll.png?ixlib=rb-4.1.0\u0026amp;q=45\u0026amp;auto=format\u0026amp;w=1000\u0026amp;fit=clip\u0022\u003E\u003Cimg src=\u0022https:\/\/images.theconversation.com\/files\/690273\/original\/file-20250910-56-q9xtll.png?ixlib=rb-4.1.0\u0026amp;q=45\u0026amp;auto=format\u0026amp;w=754\u0026amp;fit=clip\u0022 alt=\u0022Diagram showing the evolution of amino acids to oligopeptides to complex proteins\u0022\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EThe Dayhoff hypothesis proposed that large, complex proteins arose from the duplication and merging of smaller, simpler peptides over time. \u003Ca href=\u0022https:\/\/doi.org\/10.3390\/biom12060793\u0022\u003EMerski et al.\/Biomolecules\u003C\/a\u003E, \u003Ca href=\u0022http:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/\u0022\u003ECC BY-SA\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003EUsing computer models, we compared a range of P-loops from the P-loop NTPase family to a control group made of the same amino acids but in a different order. While these control loops are also found in proteins, they do not form nests.\u003C\/p\u003E\u003Cp\u003EAlthough the P-loops and the control loops are very different in their nest-forming ability, we found that they both are able to \u003Ca href=\u0022https:\/\/doi.org\/10.1093\/molbev\/msaf055\u0022\u003Eform transient nests\u003C\/a\u003E when embedded in proteins. This meant that, contrary to popular belief, the amino acid sequence of P-loops aren\u2019t special in their ability to form nests \u2013 as would be expected if they alone were the seeds for many modern proteins.\u003C\/p\u003E\u003Ch2\u003EA Fossil Eroded Over Time\u003C\/h2\u003E\u003Cp\u003EOur work strongly suggests that while the P-loop is a molecular fossil, the true nature of its form billions of years ago may have been eroded by the sands of time.\u003C\/p\u003E\u003Cp\u003EFor example, when \u003Ca href=\u0022https:\/\/doi.org\/10.1093\/molbev\/msaf055\u0022\u003Ewe repeated our simulations\u003C\/a\u003E in a different solvent \u2013 specifically methanol \u2013 we found that P-loops situated in their parent proteins were able to regain some of their ability to form nests. This doesn\u2019t mean that being in methanol drove the first proteins with P-loops to form the nests critical for life. But it does emphasize the importance of considering the surrounding environment when studying peptides and proteins.\u003C\/p\u003E\u003Cp\u003EJust as archaeologists know to be careful in how they \u003Ca href=\u0022https:\/\/theconversation.com\/was-it-a-stone-tool-or-just-a-rock-an-archaeologist-explains-how-scientists-can-tell-the-difference-251126\u0022\u003Einterpret physical fossils\u003C\/a\u003E, historians of protein evolution could take similar care in their interpretation of molecular fossils. Our results complicate the current understanding of early protein evolution and, consequently, some aspects of the origins of life.\u003C\/p\u003E\u003Cp\u003EIn resetting the field\u2019s broader understanding of how these crucial proteins emerged, scientists are poised to start rewriting our own evolutionary history on this planet.\u003C!-- Below is The Conversation\u0027s page counter tag. Please DO NOT REMOVE. --\u003E\u003Cimg src=\u0022https:\/\/counter.theconversation.com\/content\/259271\/count.gif?distributor=republish-lightbox-basic\u0022 alt=\u0022The Conversation\u0022 width=\u00221\u0022 height=\u00221\u0022\u003E\u003C!-- End of code. If you don\u0027t see any code above, please get new code from the Advanced tab after you click the republish button. The page counter does not collect any personal data. More info: https:\/\/theconversation.com\/republishing-guidelines --\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis article is republished from \u003C\/em\u003E\u003Ca href=\u0022https:\/\/theconversation.com\u0022\u003E\u003Cem\u003EThe Conversation\u003C\/em\u003E\u003C\/a\u003E\u003Cem\u003E under a Creative Commons license. Read the \u003C\/em\u003E\u003Ca href=\u0022https:\/\/theconversation.com\/molecular-fossils-offer-microscopic-clues-to-the-origins-of-life-but-they-take-care-to-interpret-259271\u0022\u003E\u003Cem\u003Eoriginal article\u003C\/em\u003E\u003C\/a\u003E\u003Cem\u003E.\u003C\/em\u003E\u003C\/p\u003E","summary":"","format":"full_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EThe questions of how humankind came to be, and whether we are alone in the universe, have captured imaginations for millennia. But to answer these questions, scientists must first understand life itself and how it could have arisen.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"The questions of how humankind came to be, and whether we are alone in the universe, have captured imaginations for millennia. But to answer these questions, scientists must first understand life itself and how it could have arisen."}],"uid":"27469","created_gmt":"2025-09-17 13:13:05","changed_gmt":"2025-09-18 16:37:43","author":"Kristen Bailey","boilerplate_text":"","field_publication":"","field_article_url":"","location":"Atlanta, GA","dateline":{"date":"2025-09-16T00:00:00-04:00","iso_date":"2025-09-16T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"678052":{"id":"678052","type":"image","title":"ATP synthase is an enzyme that has been using phosphate to generate life\u2019s energy for millions of years.","body":"\u003Cp\u003EATP synthase is an enzyme that has been using phosphate to generate life\u2019s energy for millions of years. \u003Ca href=\u0022https:\/\/www.gettyimages.com\/detail\/photo\/synthase-enzyme-complex-illustration-royalty-free-image\/1328336178\u0022\u003ENanoclustering\/Science Photo Library via Getty Images\u003C\/a\u003E\u003C\/p\u003E","created":"1758125600","gmt_created":"2025-09-17 16:13:20","changed":"1758125600","gmt_changed":"2025-09-17 16:13:20","alt":"ATP synthase is an enzyme that has been using phosphate to generate life\u2019s energy for millions of years.","file":{"fid":"262030","name":"file-20250910-66-w313hf.jpg","image_path":"\/sites\/default\/files\/2025\/09\/17\/file-20250910-66-w313hf.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2025\/09\/17\/file-20250910-66-w313hf.jpg","mime":"image\/jpeg","size":182818,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2025\/09\/17\/file-20250910-66-w313hf.jpg?itok=wnfLg1eK"}}},"media_ids":["678052"],"related_links":[{"url":"https:\/\/theconversation.com\/molecular-fossils-offer-microscopic-clues-to-the-origins-of-life-but-they-take-care-to-interpret-259271","title":"Read This Article on The Conversation"}],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"},{"id":"85951","name":"School of Chemistry and Biochemistry"}],"categories":[],"keywords":[{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Ch5\u003EAuthors:\u003C\/h5\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/theconversation.com\/profiles\/caroline-lynn-kamerlin-2416162\u0022\u003ECaroline Lynn Kamerlin\u003C\/a\u003E, professor of chemistry and biochemistry, \u003Ca href=\u0022https:\/\/theconversation.com\/institutions\/georgia-institute-of-technology-1310\u0022\u003E\u003Cem\u003EGeorgia Institute of Technology\u003C\/em\u003E\u003C\/a\u003E\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/theconversation.com\/profiles\/liam-longo-2423771\u0022\u003ELiam Longo\u003C\/a\u003E, specially appointed associate professor, Earth-Life Science Institute, \u003Ca href=\u0022https:\/\/theconversation.com\/institutions\/institute-of-science-tokyo-6525\u0022\u003E\u003Cem\u003EInstitute of Science Tokyo\u003C\/em\u003E\u003C\/a\u003E\u003C\/p\u003E\u003Ch5\u003EMedia Contact:\u003C\/h5\u003E\u003Cp\u003EShelley Wunder-Smith\u003Cbr\u003E\u003Ca href=\u0022mailto:shelley.wunder-smith@research.gatech.edu\u0022\u003Eshelley.wunder-smith@research.gatech.edu\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":[],"slides":[],"orientation":[],"userdata":""}}}