A missing piece of Earth’s evolutionary timeline may have been found. Using computer modelling, a team of scientists explored how working backwards from modern biochemistry could help map how simple, non-living chemicals first occur Earth gave rise to the complex molecules that led to the emergence of life as we know it.
Scientists believe that modern metabolism—the life-sustaining biochemical processes that occur in living things—evolved from the primitive geochemical environment of the ancient Earth, drawing on available materials and energy sources. While this is an interesting idea, evidence for the transition from primitive geochemistry to modern biochemistry is still lacking.
Past modeling studies have provided valuable insights, but they’ve always hit a snag: their models of metabolic evolution have consistently failed to produce many of the complex molecules used by modern life—and it’s not clear why.
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Notably, there is uncertainty about the continuity in this metabolic timeline, specifically the extent to which ancient biochemical processes that may have disappeared during time they shaped the metabolic processes we know today.
“In particular, chemical reactions unrelated to biochemistry were reported as missing steps in early biosynthetic pathways, suggesting that records of these chemical transformations were lost throughout evolutionary history,” said the study team from the Tokyo Institute of Technology and California. The Institute of Technology wrote in an article describing the new missing article. “It remains unclear to what extent the ‘extinct’ biochemistry is necessary to allow the generation of modern metabolism from the early Earth environment.”
To unravel this puzzle, scientists have tried to model the possible evolutionary pathways that could have brought modern metabolism from its early Earth ancestors to the present. They therefore investigated biochemical evolution at the biosphere level, meaning at the scale of the entire ecosystem, and integrated influences and factors such as geochemical and atmospheric environments, as well as how organisms may interact.
“The roots of biochemistry have long been thought to lie in the geochemistry of the early Earth,” said Seán Jordan, associate professor of biogeochemistry and astrobiology at Dublin City University, who was not involved in the study, told Space.com. “The suggestion that remnants of ancient metabolic pathways may be hidden in the modern biosphere, and yet to be discovered, is fascinating and exciting.”
The team used the Kyoto Encyclopedia of Genes and Genomes database, which cataloged just over 12,000 biochemical reactions, as a model repository for all the possible biochemical reactions that could have occurred and evolved during the timeline studied. The researchers then simulated the expansion of a web of chemical reactions starting with the set of initial compounds that would have been found on the early Earth. These included various metals and inorganic molecules such as iron, hydrogen sulfide, carbon dioxide, and ammonia, as well as organic substrates that may have formed through ancient carbon-fixing reactions.
“Using a network expansion algorithm to trace the path from early geochemistry to complex metabolic networks appears to be a solid, iterative approach to this question,” Jordan said.
However, as with other modeling experiments, the scientists’ model initially failed to reproduce even a fraction of the molecules used in modern biochemical processes, leaving the vast majority unobtainable from the seed compounds. Assuming these results were limited because the data set included only known cataloged biochemical reactions, the researchers expanded the Kyoto database to also include a set of hypothetical biochemical reactions and added 20,183 new pathways.
Repeating the experiment with this expanded reaction set resulted in only a modest increase in range, “suggesting that neither currently cataloged nor predicted biochemistry contains the transformations required to reach the vast majority of known metabolites”.
The authors noticed that a key precursor to a class of compounds called purines, which are important building blocks for biological molecules such as DNA and RNA, was not found within the scope of the model’s expansion. In fact, a quick test in which adenine, a common purine derivative, was added to the pool of seed compounds resulted in about a 50% increase in the number of modern biomolecules the model was able to predict.
Further experiments confirmed what the authors called a “purine bottleneck” that appears to prevent metabolism from geochemical precursors in the model. The problem appears to be related to a dataset of modern biochemical reactions where the production of purines such as adenosine triphosphate (ATP) is autocatalytic. This means that several steps in the ATP synthetic pathway require ATP itself – without ATP, new ATP cannot be made. This self-cycling caused the model to stall.
To solve the bottleneck, the researchers hypothesized that this self-catalyzing dependence may have been more “relaxed” in primitive metabolic pathways, as inorganic molecules known as polyphosphates could have performed the role ATP currently plays. By substituting ATP in the database reactions (only eight in total required this change), it was possible to achieve almost all of the current basal metabolism.
“We may never know for sure, but our research has provided an important piece of evidence: only eight new reactions, all of which resemble common biochemical reactions, are needed to link geochemistry and biochemistry,” said Harrison Smith, one of the authors of the study. Press Release. “This does not prove that the space of missing biochemistry is small, but it does show that even reactions that have disappeared can be rediscovered from the traces left behind by modern biochemistry.”
“The big question that remains unanswered is whether we can show experimentally that steps from geochemistry to biochemistry are possible along such a trajectory [this]”These findings should encourage others in the field to continue investigating this transition.” It shows us that the chemistry blueprint that led to the origin of life can be found in existing biochemistry.”
The study was published in March in the journal Nature Ecology & Evolution.