A research group in Japan has reported creating a test tube world of molecule that spontaneously evolved both complexity and cooperation after a lengthy experiment. Over hundreds of hours of replication, a single type of RNA evolved into five different species of hosts and parasites that coexisted in harmony and cooperated to survive.

The researchers wrote that their experiment showed that the development of complexity through Darwinian evolution is a critical step for the emergence of life.

When a replicating molecule complexifies in a test tube, we can see what can happen.

Sijbren Otto, a professor of systems chemistry at the University of Groningen in the Netherlands who was not involved in the study, said that this was the first step towards evolving a complex network of replicators in the lab.

The work by Mizuuchi and his colleagues was hailed as a great proof of concept for how a minimal system can complexify. She said it was a very significant advance.

The Spawn of Spiegelman’s Monster

In the 1960s, Sol Spiegelman created what he called the little monster in his laboratory. His little monster was not green, square-browed, growling or even alive, despite the resemblance to the movie "Frankenweenie". It was a synthetic molecule that was used to fill test tubes.

Profile photo of researcher Sol Spiegelman.

The monster was based on a strand ofRNA. The biologists discovered that he could reproduce it by heating and mixing it with the replicase and the building blocks. He realized that his molecule was getting smaller over time and that the copies that shed unnecessary genes were more likely to be collected in samples and transferred to new test tubes. The pressure of natural selection had begun to change his molecule into a better one to survive inside the glass world.

Eugene Koonin, a National Institutes of Health distinguished, said that these studies were the world's first experimental demonstration of Darwinian evolution.

The work of Spiegelman inspired decades of further study and provided fuel for the hypothesis that life sprang from self-replicatingRNA. Could a single replicator evolve into a complex network of multiple replicators?

When Norikazu Ichihashi was an associate professor of bioinformatic engineering at Osaka University in Japan, he set out to learn the answer by tweaking the test tube world.

Ichihashi and his team have developed a molecule that can make copies of RNA. The scientists needed to add ribosomes and other gene translation machinery to translate the molecule's code. They put the machinery inside the droplets and put them in a mixture of raw materials.

After years of waiting, came years of tedious mixing.

The long-term experiment involved stirring the mixture and adding new droplets with fresh translation systems to induce replication. They analyzed the concentrations in the test tubes and froze the samples from the latest mixture. Every half year or so, they take large batches of the collected samples and sequence them to see if the RNA has changed.

Evolution in Test Tubes

The researchers reported interesting results after 215 hours and 43 rounds of replication in the Proceedings of the National Academy of Sciences. The originalRNA was replaced by two otherRNAs. The researchers said that one could use its own replicase to copy itself. Theparasite needed to borrow the gene expression machinery of the hosts.

When Ichihashi and his colleagues extended the experiment to 120 rounds of replication, they discovered that one of the hosts had evolved two different parasites. The number of lineages had increased, but so had the complexity of their interactions. The parasites had developed a defense against obstacles, but the hosts had also developed a way to interfere with the parasites' ability to hijack their resources. The parasites seemed to be evolving with the hosts.

The populations of parasites and hosts were very variable as they competed in evolutionary arms races. Ichihashi is a professor at the University of Tokyo.

By round 130, another host had evolved, thanks to the researchers. One of the parasites disappeared by round 160, and another appeared later. By round 190, the researchers had found out that the huge dynamic swings in the population of each lineage had begun to give way to smaller waves. The stabilization suggested that the lineages were not competing to replicate. They had begun to interact as a network and cooperate in a stable state.

Taro Furubayashi, who was a PhD student in Ichihashi's lab at the time and is now a research fellow at the University of Tokyo, was floored by the findings. They aremere molecules, and it is pretty unexpected.

Cooperative Parasites Do Their Share

Koonin agrees that the findings are striking. The results are more complex and rich, but it is fully compatible with Spiegelman's setup. They watched a single molecule replicate and gather mutations under natural selection, but then went further by letting the diverging molecule evolve into a community under one another's influence, just as communities of living cells, animals or people would. The researchers explored some of the rules governing what it takes for complex communities to become stable and enduring.

Some of the results confirmed the predictions of earlier studies of how complexity can arise in organisms. A study from Koonin's lab suggested that parasites were inevitable in the emergence of complexity.

Without parasites, this level of diversification is probably not possible. Both sides of parasites and their hosts are put on each other.

The critical role of cooperation was a surprising fundamental principle. Some of the five lineages were more cooperative than others. One of the three hosts had evolved into a super cooperator that could replicate itself and all the other lineages, the other two hosts could only replicate themselves.

The role of cooperation has been overlooked because scientists have focused on studies of competition in evolution.

The system that Ichihashi and his colleagues observed was the focus of the cooperation among the RNAs. The researchers hope that by adjusting the natural selection criteria inside the test tubes, it will be possible to force the RNAs to evolve a completely different function.

A Different Destiny

David Deamer is a research professor of biomolecular engineering at the University of California, Santa Cruz. The paper is a good one, but he noted that what happened in the laboratory may not translate to what happened at the dawn of life.

The scenario in Ichihashi's lab could not reflect what happened at the start of life because the experiments depended on translation machinery from E. coli.

Figure that shows how an RNA molecule evolved into several distinct lineages with complex interactions.

Koonin thinks that if researchers were able to evolve complexity using self-replicating systems of molecules, they would see something similar to the networks depicted in the paper.

The study suggests that once you have solved the problem of accurate replication with molecule at this level of complexity, they will complexify further.

Carrying on with their work, Ichihashi and his colleagues wanted to see if they could re-create the same sustainable network in a separate experiment. Ichihashi said that while four of the lineages continued to replicate and survive 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884 888-349-8884

One possibility is that the system was even more complex than the researchers thought, and that they missed a critical part of the system. Ichihashi's group confirmed with theoretical models that the four remaining lineages could be replicated and that the extinction of at least one of the others was possible. The counterintuitive discovery that knocking out one of the parasites would lead to the extinction of its host was pointed out by their simulation.

The researchers are waiting to see if their network will complexify further. They have begun similar experiments that use DNA.

We can't predict what will happen in the future, Ichihashi said.