Cells depend on enzymes to carry out their chemistry, while the protein enzymes familiar from textbooks are made by cells. That apparent circularity raises an intriguing question about the origin of life: how could either have emerged without the other?
The difficulty is that the first steps towards life need not have involved either a modern cell or a modern protein enzyme. Researchers instead investigate how simpler chemical reactions, molecules capable of carrying information, and physical compartments could have become linked. “Enzymes or cells first?” is a useful starting question, but it leaves out much of that chemistry.
Catalysis does not have to begin with a protein
A catalyst speeds a chemical reaction without being consumed overall by that reaction. Present-day life relies heavily on protein catalysts, but catalytic activity is not exclusive to proteins. Minerals and smaller molecules can also assist reactions, while some RNA molecules act as enzymes themselves.
Different origin-of-life hypotheses place different emphasis on these ingredients. Metabolism-first models explore how networks of chemical reactions might have sustained one another before modern genes existed. Other approaches put heritable molecules or compartments closer to the centre of the story. These are families of ideas, rather than two competing accounts in which a fully formed cell or enzyme simply appears first. Jowett’s 2017 review surveys these distinctions and their unresolved problems.
RNA changes the question
RNA is especially interesting because its sequence can carry information and its folded structure can support catalysis. A catalytic RNA is called a ribozyme. This combination underlies the RNA-world hypothesis: RNA may once have played a larger role in both heredity and chemistry, before the division of labour found in cells today.
The hammerhead ribozyme offers a concrete example of RNA catalysis. In a 2006 structural study, Monika Martick and William Scott showed how interactions away from its active site help arrange the molecule for cleavage of an RNA strand. The structure illustrated here comes from that research. It demonstrates a capability of RNA; it is not a reconstruction of the first catalyst on Earth, and cleavage is not the same thing as self-replication.
A reaction network also needs a way to evolve
Keeping chemistry going is only part of the challenge. A system also needs to transmit differences that can affect the success of later generations.
In a 2010 modelling study, Vera Vasas, Eörs Szathmáry and Mauro Santos examined a proposed system in which assemblies reproduce their molecular composition rather than copy a genetic sequence. They found that inaccurate inheritance prevented fitter compositions from being maintained by selection in the model studied.
That result identifies a difficulty for that particular route to evolvable chemistry. It does not establish that all metabolism-first scenarios are impossible, or prove that an RNA world was the historical starting point.
Compartments bring the ingredients together
Protocell research asks how simple compartments could help connect these functions. A boundary can keep some molecules together and separate an internal chemical environment from its surroundings. Yet a compartment must also obtain material and energy, and eventually support growth, reproduction and inheritance.
Gözen and colleagues’ 2022 review describes experimental approaches to these problems. Building a compartment that grows, or placing a reaction inside one, tests a possible step. Neither achievement on its own recreates the transition from nonliving chemistry to an evolving cell.
The question therefore becomes more specific: which combinations of chemistry, information and compartments could work together under plausible early-Earth conditions? Experiments can establish that a proposed step is possible and expose where a model fails. Establishing which sequence actually occurred requires a different level of evidence. The studies discussed here provide pieces of that explanation, not a completed history of life’s beginning.
Related reading
Explore another example of molecular organisation in our article on fractal patterns formed by a natural enzyme.
References
- Jowett, P. (2017). Myth and fact in the origins of cellular life on Earth. Bioscience Horizons, 10, hzx017. Review.
- Martick, M. and Scott, W. G. (2006). Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell, 126, 309–320. Research paper. PDB 3ZD5.
- Vasas, V., Szathmáry, E. and Santos, M. (2010). Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life. PNAS, 107, 1470–1475. Modelling study.
- Gözen, I. et al. (2022). Protocells: Milestones and Recent Advances. Small, 18, 2106624. Review.
Update note: Revised on 1 October 2026 to distinguish protein enzymes, RNA catalysts, heritable chemistry and protocells, and to clarify the limits of the cited models. References and the structural illustration were updated. The original publication date is retained.
