Scientists discover billions of years of history in the chemistry of life

The origin of life on Earth has long been a mystery that has eluded scientists. A key question is how much of the history of life on Earth is lost over time. It is quite common for a single species to “go extinct” using a biochemical reaction, and if this happens in enough species, such reactions could effectively be “forgotten” by life on Earth.

But if the history of biochemistry is full of forgotten reactions, is there any way to find out? This question inspired researchers at the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology and the California Institute of Technology (CalTech) in the United States. They believed that forgotten chemistry would appear as discontinuities or “breaks” in the path taken by chemistry from simple geochemical molecules to complex biological molecules.

The early Earth was rich in simple compounds such as hydrogen sulfide, ammonia, and carbon dioxide, molecules not typically associated with sustaining life. But billions of years ago, primitive life relied on these simple molecules as a source of raw material. As life evolved, biochemical processes gradually transformed these precursors into compounds still present today. These processes represent the first metabolic pathways.

To model the history of biochemistry, ELSI researchers – Specially Appointed Associate Professor Harrison B. Smith, Specially Appointed Associate Professor Liam M. Longo, and Associate Professor Shawn Erin McGlynn, working with Research Scientist Joshua Goldford of CalTech – needed an inventory of all known biochemical reactions, to understand what types of chemistry life is capable of performing.

They turned to the Kyoto Encyclopedia of Genes and Genomes database, which has cataloged more than 12,000 biochemical reactions. With the reactions in hand, they began to model the gradual development of metabolism.

Previous attempts to model the evolution of metabolism in this way had failed to produce the most widespread complex molecules used in contemporary life. However, the reason was not entirely clear. As before, when the researchers ran their model, they found that only a few compounds could be produced. The research is published in the journal Ecology and evolution of nature.

One way around this problem is to boost stalled chemistry by manually supplying modern compounds. The researchers took a different approach: They wanted to determine how many reactions were missing. And their hunt led them back to one of the most important molecules in all of biochemistry: adenosine triphosphate (ATP).

ATP is the energy currency of the cell because it can be used to trigger reactions, such as protein production, that would not otherwise occur in water. ATP, however, has a unique property: the reactions that themselves form ATP require ATP. In other words, unless ATP is already present, there is no other way to produce ATP today. This cyclical dependence was the reason why the model stopped.

How to solve this “ATP bottleneck”? It turns out that the reactive part of ATP is remarkably similar to the inorganic compound polyphosphate. By allowing ATP-generating reactions to use polyphosphate instead of ATP – changing just eight reactions in total – almost all of contemporary central metabolism could be achieved. Researchers could then estimate the relative ages of all common metabolites and ask pointed questions about the history of metabolic pathways.

One such question is whether biological pathways were constructed in a linear fashion – in which one reaction after another is added sequentially – or whether pathway reactions emerged as a mosaic, in which reactions from very different ages come together to form a mosaic. form something new. The researchers were able to quantify this and found that the two types of pathways are almost equally common throughout metabolism.

But back to the question that inspired the study: How much biochemistry is lost over time? “We may never know exactly, but our research has provided an important piece of evidence: Only eight new reactions, all reminiscent of common biochemical reactions, are needed to connect geochemistry and biochemistry,” says Smith.

“This doesn’t prove that the space of missing biochemistry is small, but it does show that even reactions that have disappeared can be rediscovered from clues left by modern biochemistry,” Smith concludes.