Clues to life's beginnings found in ancient chemical reactions

Imagine a vibrant library, filled with books chronicling the rich history of life on Earth. Each book details the unique chemical reactions that have fueled life’s evolution over billions of years. 

Now, imagine that some of these books have been lost to time, leaving gaps in our understanding of how life came to be. This is the tantalizing mystery that researchers at the Earth-Life Science Institute (ELSI) and the California Institute of Technology (CalTech) have set out to explore.

Scientists have long pondered the origins of life, and a central question is how much of this history has vanished into the depths of time. Species can abandon biochemical reactions, and if this occurs across many species, such reactions could effectively be “forgotten” by life.

Quest for lost chemical reactions of life

But is there any way to tell if the history of biochemistry is riddled with forgotten reactions? 

To answer this, the ELSI and CalTech researchers embarked on a quest to trace the chemical path from simple geochemical molecules to the complex biological molecules found in living organisms today. They hypothesized that forgotten chemistry would appear as discontinuities or “breaks” in this path.

The early Earth was rich in simple compounds like hydrogen sulfide, ammonia, and carbon dioxide, which are not typically associated with sustaining life. 

Yet, billions of years ago, these compounds served as the raw materials for early life. Over time, biochemical processes gradually transformed these precursors into the compounds we find in living organisms today.

To model the history of biochemistry, the researchers needed an inventory of all known biochemical reactions. They turned to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, which contains over 12,000 cataloged reactions. 

With this vast dataset in hand, they began to model the step-by-step development of metabolism, the intricate network of chemical reactions that sustain life.

ATP reactions and life’s origins

Previous attempts to model the evolution of metabolism had stumbled, failing to produce the complex molecules used by modern life. This time, the researchers encountered the same roadblock. Their model could only generate a few compounds, and the reason was not immediately clear.

The breakthrough came when they focused on adenosine triphosphate (ATP), the universal energy currency of cells. ATP is essential for driving reactions that wouldn’t occur spontaneously, such as building proteins. 

However, ATP has a unique property: the reactions that produce ATP also require ATP. This creates a cyclic dependency, an “ATP bottleneck” that was halting the model’s progress.

To resolve this bottleneck, the researchers discovered a workaround. The reactive portion of ATP is strikingly similar to an inorganic compound called polyphosphate. 

By allowing ATP-generating reactions to use polyphosphate instead of ATP, a minor modification of just eight reactions, the model was able to generate almost all of the core metabolism found in contemporary life.

Rediscovering lost reactions

With this hurdle overcome, the researchers could now estimate the relative ages of all common metabolites and delve into the history of metabolic pathways. 

They sought to determine if biological pathways evolved linearly, with reactions added sequentially, or as a mosaic, with reactions of different ages combined to create new pathways.

The researchers found that both types of pathways are almost equally common throughout metabolism. They were also able to quantify how much biochemistry might be lost to time. 

“We might never know exactly, but our research yielded an important piece of evidence: only eight new reactions, all reminiscent of common biochemical reactions, are needed to bridge geochemistry and biochemistry,” said Smith.

“This does not prove that the space of missing biochemistry is small, but it does show that even reactions which have gone extinct can be rediscovered from clues left behind in modern biochemistry.”

This remarkable research offers a glimpse into the vast and complex history of biochemistry. It suggests that even seemingly lost reactions can be rediscovered, revealing the intricate pattern of life’s evolution. 

The journey to uncover the secrets of life’s origins continues, and with each new discovery, we gain a deeper appreciation for the remarkable story written into the chemistry of life.

The study is published in the journal Nature Ecology & Evolution.

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