A new study is challenging long-standing assumptions about how proteins evolved and what their earliest forms might have looked like. For years, scientists believed that a specific protein motif—a small, recurring sequence of amino acids—was the starting point for many of the proteins we find in organisms today. This motif, known as the Walker A motif, is found in enzymes that play an essential role in various biological functions, including energy production. However, researchers now suggest that this motif alone is not the key to understanding the origin of proteins, and its role in early life might be more complex than previously thought.

The study, published in Molecular Biology and Evolution, was led by Lynn Kamerlin, a professor at Georgia Tech, and Liam Longo, a researcher at the Earth-Life Science Institute in Tokyo. The team tested the idea that the Walker A motif could have sparked the development of proteins in early life. They did this by creating and analyzing short peptides—small pieces of proteins—based on the Walker A motif and then simulating how these peptides behave in different environments. They found that these peptides did not form the stable structures expected and were no more significant than other similar motifs.

Kamerlin and Longo’s findings suggest that the Walker A motif is not the sole origin of proteins. Instead, they propose that the motif may be an “eroded molecular fossil”—a remnant of ancient proteins whose original function has been overwritten by billions of years of evolution. Just like the presence of eyes does not mean all animals with heads evolved from those eyes, the Walker A motif’s role is part of a much larger, more complex system that allows proteins to function. The team also showed that similar motifs could form in different environments, challenging the idea that this motif was uniquely suited to the earliest life forms.

The implications of this study go beyond just understanding the origins of life. By rethinking how proteins evolved, the team’s work opens up new possibilities for biotechnology. Understanding the early evolution of proteins could help scientists design artificial proteins for various applications, from developing new drugs to improving vaccines. However, the work is still ongoing, and the next step for researchers is to investigate how these motifs became dominant over time and what other types of proteins could have emerged in the early stages of life. This study is just the beginning of a deeper exploration into the mystery of how life evolved on Earth.

References

• Demkiv, A. O., Toledo-Patiño, S., Medina-Carmona, E., Berg, A., Pinto, G. P., Parracino, A., Sanchez-Ruiz, J. M., Hengge, A. C., Laurino, P., Longo, L. M., & Kamerlin, S. C. L. (2025). Redefining the limits of functional continuity in the early evolution of p-loop ntpases. Molecular Biology and Evolution, 42(4), msaf055. https://doi.org/10.1093/molbev/msaf055
• Malone, T. & Georgia Institute of Technology. (2025, May 13). Protein problem: Researchers challenge fundamental assumption in evolutionary biochemistry. Phys.Org; Georgia Institute of Technology. https://phys.org/news/2025-05-protein-problem-fundamental-assumption-evolutionary.html