
Tiny protein factories, or ribosomes, have been made to self-replicate outside a living cell for the first time. The achievement is a crucial step towards building self-replicating artificial cells from scratch and understanding how the first living things started reproducing themselves.
Ribosomes are where the genetic code gets translated into proteins – complex molecules that make up the machinery of living cells. In order for the earliest life to get going, many researchers think ribosomes must have been able to assemble and replicate before there were cells.
But ribosome self-replication is incredibly complex, involving around 200 types of molecules coming together in just the right way, so scientists have struggled to make this happen in the lab.
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“Ribosomes are solely responsible for protein synthesis in all known forms of life. How ribosomes self-replicate themselves is a big question,” says at Kyoto University in Japan.
Now, Aoki and his colleagues have finally established the conditions required for ribosomes to replicate themselves outside a cell – after seven years working to optimise the reaction mixture.
The researchers put DNA coding for ribosome components along with ribosomes derived from E. coli cells into a tube. To that, they added a tweaked version of the liquid, or cytoplasm, extracted from E. coli cells.
Guided by an artificial intelligence, the researchers established the precise molecular cocktail that would kick-start ribosome self-replication. The winning formula enabled ribosomes to produce new ones within 3 hours.
“We suspected it was a false positive. However, no matter how many times we repeated the experiment and analysed it from other approaches, we found that the signal was indeed observed,” says Aoki.
It is unclear whether the new generation of ribosomes then self-replicated or how many rounds of replication are possible.
“Nascent ribosomes may self-replicate themselves to produce another set of ribosomes. However, there is currently no good way to separate signals [between these ribosome generations],” says Aoki, whose team is working to resolve this question.
Further work will also be needed to pinpoint all of the components within the E. coli cell extract that are critical for the reaction.
Nevertheless, the achievement is a huge step towards building self-replicating artificial life from scratch and will help shed light on how life got started.
“Being able to construct a ribosome that makes a copy of itself, outside of a live cell, is a huge milestone resulting from large feats of engineering,” says at the University of Minnesota. “It’s significant not only for making synthetic cells, but also for the studies of the origin of life.”
“This is indeed exciting work,” says at Eindhoven University of Technology in the Netherlands. “Ribosomes are one of the most complex machines in our cells. Making them in the test tube solves one of the stumbling blocks to construct self-replicating artificial cells.”
Learning how to create artificial cells could help researchers develop new research tools and therapies. Quoting the theoretical physicist Richard Feynman, Aoki says: “What I cannot create, I do not understand.”
Reference: bioRxiv, DOI: