The RNA world hypothesis, which posits that early life ran on RNA alone, remains an open question for science as researchers weigh the mechanics of prebiotic chemistry.
The Genetic Deadlock
Life appeared on a barren Earth some 4 billion years ago, requiring self-replication to reliably store and copy genetic information. Modern cells rely on DNA to encode proteins, while RNA carries that information to build them. Yet proteins participate in every step of this cycle, creating a distinct chicken-and-egg problem.
Useful proteins cannot be made without DNA, but proteins are needed to make DNA in the first place. A discovery in the late 1980s broke this deadlock when researchers found that some RNAs can act as catalysts that speed up chemical reactions.
Ribozymes and Early Evolution
Scientists named these catalytic RNA molecules ribozymes after protein enzymes, suggesting RNA could handle both genetic storage and chemical work. Physicist-turned-biologist Walter Gilbert championed the resulting RNA world hypothesis. In 1996, researchers created a ribozyme that could stitch individual nucleotides together to form RNA, raising the prospect of replication.
Copying errors would introduce mutations, allowing natural selection to favor variants that copied themselves faster. These evolving molecular systems offered a plausible path toward the first living protocells.
Laboratory Hurdles
In 2019, RNA biologist Gerald Joyce and colleagues at the Salk Institute tested a method for evolving synthetic ribozymes in the lab. They discovered that mutations introduced in each round of evolution tended to kill off the ribozymes’ catalytic activity.
Spontaneous assembly experiments have only yielded RNAs about 10 to 15 nucleotides long. Making the jump from those tiny fragments to large, self-sustaining molecules in a primordial pool presents a major challenge.
Small Replicators
Recent work from biologist Philipp Holliger and colleagues at the MRC Laboratory of Molecular Biology shows self-replicating RNAs can be much smaller. The team identified a 45-nucleotide molecule named QT45 that can seize and copy another RNA strand.
In principle it can copy any sequence,
Philipp Holliger, MRC Laboratory of Molecular Biology
Holliger added that getting such a molecule spontaneously does not seem an unreasonable ask.
The researchers found two other comparably small RNAs with similar activity within a starting pool of around 10 trillion different molecules, suggesting this copying ability might be common among random RNAs.
