Caltech researchers have identified a novel chemical reaction that could explain the formation of the building blocks of DNA and RNA, the molecules that encode all of life's functions. The work is an important step toward understanding how life may have emerged on Earth and potentially elsewhere in the universe, showing the straightforward and efficient pathways through which simple molecules can give rise to complex biological precursors.
The study is described in a paper appearing in the journal Icarus on May 14. The research was conducted in the laboratory of the late Yuk L. Yung, professor of planetary science and senior research scientist at the Jet Propulsion Laboratory (JPL), which Caltech manages for NASA.
In the first billion years of our planet's history, Earth was a dynamic place, as volcanoes erupted into the atmosphere and oceans of liquid water splashed across the planet. At some point more than 3 billion years ago, the right chemical conditions occurred for the development of living organisms. Understanding the so-called prebiotic chemistry that led to the origin of life is a major field of study.
Every life form on Earth stores its genetic information in the form of nucleic acids: DNA and RNA. These molecules are built from molecules called nucleotides that are made up of five canonical nucleobases: adenine, thymine, guanine, cytosine, and uracil. Like letters combining to form complex sentences, nucleobases string together to create long chains of nucleic acids. But nucleobases themselves are complex chemical structures. How did they form in the early Earth's environment?
The new study, led by former Caltech postdoctoral scholar Jeehyun Yang (now of the University of Chicago), discovers a new chemical mechanism that could explain the formation of nucleobases.
Yang first sought to identify the building blocks of the building blocks themselves. Using a computational software, he and his team determined which molecular structures were common to all five types of nucleobases under the temperatures and pressures of the early Earth's environment. Yang found most of the usual suspects-nitrogen, carbon dioxide, methane-but also, surprisingly, benzene. Benzene is a hexagonal ring of hydrogen and carbon atoms, a shape similar to nucleobases.
But would benzene be stable on the early Earth? Yang showed that benzene was indeed stable in atmospheres dominated by nitrogen or carbon dioxide-and Earth's current atmosphere is mostly nitrogen.
Yang then demonstrated that benzene can react with a gas called hydrogen cyanide (HCN), incorporating the necessary nitrogen atoms into its ring-like structure to create the precursors to nucleobases. This illustrated a novel chemical pathway for forming nucleobases. Previous suggested mechanisms to construct nucleobases out of HCN were complicated, requiring many unlikely chemical reactions. This new pathway offers a much simpler and more efficient explanation for the formation of nucleobases.
"This is a possible scenario for what could have happened in the early Earth's atmosphere," Yang says. "Benzene could have met with HCN and, spurred on by photochemical energy from ultraviolet light or lightning, carried out the reaction to incorporate nitrogen into the carbon structure. The resulting structure would be soluble in water and could have dissolved into the ocean, where we suspect life first originated."
While it remains unclear how often such chemistry would have needed to occur to support the emergence of life, if benzene and HCN were continuously available in early Earth environments, this chemistry could have operated repeatedly and potentially provided an ongoing source of prebiotic molecules. How long this chemistry needed to occur before single-celled organisms could evolve is still an open question.
The team next plans to demonstrate that these reactions can occur in the laboratory.
The study is one of the final papers from Yung's laboratory before his passing in March 2026. Yung's research over his long career often focused on understanding the chemistries underpinning planetary evolution and the origins of life. In awarding Yung the 2015 Gerard P. Kuiper Prize, the American Astronomical Society's Division for Planetary Sciences described Yung as "a founding father of planetary atmospheric chemistry and one of the most influential researchers in the field."
The paper is titled "Novel chemical pathways for the formation of nucleobase precursors via benzene p-bond addition to HCN." In addition to Yang and Yung, co-authors are Danica Adams (PhD '23) of Harvard University and JPL research scientist Renyu Hu (now of Penn State University). Funding was provided by NASA.
