The origin of life on Earth has puzzled scientists for ages.
A key question is how much of life’s early history is lost over time. Often, species stop using certain biochemical reactions, and if this happens widely enough, those reactions could be forgotten entirely.
Researchers from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology and the California Institute of Technology (CalTech) tackled this mystery.
They wondered if forgotten biochemical reactions could be identified by finding breaks in the chemical pathways that lead from simple molecules to complex biological ones.
Billions of years ago, early Earth was rich in simple compounds like hydrogen sulfide, ammonia, and carbon dioxide—molecules we don’t usually associate with life.
But ancient life forms used these simple molecules to create the first metabolic pathways, the chemical processes essential for life.
To understand the history of these processes, ELSI researchers, including Professors Harrison B. Smith, Liam M. Longo, and Shawn Erin McGlynn, along with CalTech’s Joshua Goldford, needed to examine all known biochemical reactions.
They used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which catalogs over 12,000 biochemical reactions. This massive inventory allowed them to model the step-by-step development of metabolism.
Previous attempts to model the evolution of metabolism often failed to recreate the complex molecules used by modern life. When the researchers ran their model, it stalled, producing only a few compounds. The research, published in Nature Ecology & Evolution, aimed to find out why.
One way to address this issue is to manually add modern compounds to the model. However, the researchers took a different approach. They wanted to see how many reactions were missing. Their search led them to one of biochemistry’s most crucial molecules: adenosine triphosphate (ATP).
ATP is the cell’s energy currency, essential for driving reactions like protein synthesis that wouldn’t happen in water. However, ATP production itself requires ATP, creating a cyclic dependency that stalled their model.
The solution? Polyphosphate, an inorganic compound with a reactive portion similar to ATP.
By allowing ATP-generating reactions to use polyphosphate instead, the researchers modified just eight reactions. This small change enabled the model to produce nearly all of contemporary core metabolism. They could then estimate the ages of common metabolites and explore the history of metabolic pathways.
One question they explored was whether biological pathways developed linearly, with one reaction added after another, or as a mosaic, combining reactions of different ages. They found that both types of pathways are equally common across metabolism.
Returning to the initial question—how much biochemistry is lost to time? “We might never know exactly, but our research yielded an important piece of evidence: only eight new reactions, all similar to common biochemical reactions, are needed to bridge geochemistry and biochemistry,” says Smith.
“This doesn’t prove the space of missing biochemistry is small, but it shows that even extinct reactions can be rediscovered from clues in modern biochemistry,” concludes Smith.
This study sheds light on the hidden chemistry of life’s origins and offers new insights into the ancient processes that paved the way for the complex life we see today.
