Most scientists are in agreement that life began on Earth about 3.8 billion years ago with the emergence of simple, single-celled organisms. But how did the building blocks of life begin in the first place?
Scientists at Furman University and The Scripps Research Institute in California have published a new study that might just help answer that question.
The study, which was published in the January 2018 edition of the science journal Nature Communications, demonstrates how key chemical reactions that support life today could have been carried out with ingredients likely present on Earth some four billion years ago.
“This research establishes a potential chemical precursor to the citric acid cycle, which may have been functional on the early Earth prior to the origins of life,” said Greg Springsteen, a chemistry professor at Furman University and co-author of the study.
The citric acid cycle, or TCA cycle, is an eight-step chain of chemical reactions that convert carbohydrates, fats, and proteins into carbon dioxide and adenosine triphosphate, which cells use for energy. Every oxygen-breathing organism relies on the TCA cycle to release stored energy in cells.
In previous studies, researchers attempted to formulate a recipe for early life by trying to replicate the chemical reactions that form today’s TCA cycle. But some of the molecules, or ingredients, needed to sustain the cycle were likely too fragile to withstand the harsh environment of the early Earth.
Springsteen and his co-authors instead looked to replicate the reactions by using ingredients found on early Earth. Now, after five years of experiments, they’ve identified feasible ingredients among two non-biological cycles of chemical reactions, the HKG cycle and the malonate cycle. Both cycles resemble the TCA cycle in several ways, including the ability to introduce new source material into the cycle.
The newly published study suggests that the two cycles could have come together to form a primitive version of the TCA cycle, which would have provided the chemical architecture necessary to jumpstart life on Earth. It also reveals that at the center of these reactions is a molecule called glyoxylate, which previous studies show could have been available on early Earth and is part of the modern TCA cycle.
Springsteen said the guiding research hypothesis behind the study is the notion that “the chemistry of life” is driven by metabolism — a network of reactions that occur inside the body and provide adequate energy for life processes. The types of reactions, and the routes they take in this metabolism are remarkably consistent across living systems.
The researchers used their understanding of reaction mechanisms to look for underlying chemical patterns. In the lab, they determined whether these patterns are sustainable in a reaction flask without the aid of complex biological machinery.
“The modern biological TCA cycle is a central metabolic pathway that releases stored energy but requires the complex machinery of life to function,” said Springsteen. “The identified precursor pathways are functional within a reaction flask outside of life, and may have been the template from which a TCA metabolism arose.”
As for the future, Springsteen and his co-authors plan to conduct additional research to determine how these chemical reactions could have become as sustainable as the TCA cycle is today. The researchers think that as enzymes (proteins that act as catalysts within living cells) became available, they could have led to the replacement of non-biological molecules in these fundamental reactions to make them more elaborate and efficient.
“The chemistry could have stayed the same over time, it was just the nature of the molecules that changed,” said Ramanarayanan Krishnamurthy, associate professor of chemistry at The Scripps Research Institute and co-author of the study. “The molecules evolved to be more complicated over time based on what biology needed.”
Springsteen said the research, which was funded by the National Science Foundation and NASA through the Center for Chemical Evolution, is not only essential to our scientific understanding of life on Earth but also our search for extraterrestrial life.
“This may help us to understand where to look out in the universe for other life. If we can identify those kinds of environments that allow these precursor reaction pathways to occur we might know exactly where in the universe we are most likely to find living systems,” said Springsteen. “I think that’s why NASA is interested in funding our work.”
Springsteen acknowledged that one of the two TCA cycle precursors described in the new study were established in experiments carried out by two undergraduates, Chandler Joel Rhea and Julia Nelson.
Nelson, a former chemistry major who is now studying at the Medical University of South Carolina, ran some of the foundational experiments of the project in 2013. She pursued the research for three years, including the summer following graduation in 2015.
Rhea, a junior majoring in neuroscience at Furman University, joined Springsteen’s team in spring 2016 and continued investigating the project through its completion in fall 2017. He plans to begin working on a follow-up project this spring.
“The success we’ve seen on the project demonstrates the power and importance of faculty working directly with undergraduates as colleagues outside of the classroom,” said Springsteen.
For more information, visit furman.edu.