
An artificial “minimal cell” that has had all but the most essential genes stripped out can evolve just as fast as a normal cell. The finding shows that organisms can rapidly adapt, even with an unnatural genome that provides little flexibility.
“It appears there’s something about life that’s really robust,” says at Indiana University in Bloomington. “We can strip it down to just the bare essentials,” he says, but that doesn’t stop evolution going to work.
Lennon and his team studied a bacterium called Mycoplasma mycoides, a parasite that lives in the guts of animals like cows. Because it gets most of its nutrients from its host, .⳦Ǿ has naturally lost a lot of genes.
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In 2016, researchers led by Craig Venter at the in California reported that they had stripped the bacterium’s 901-gene genome back even further, to just 493 genes. The resulting synthetic organism, .⳦Ǿ JCVI-syn3B, has a “minimal genome”, the smallest of any known free-living organism.
M. mycoides JCVI-syn3B can grow and divide normally, but Lennon wondered what would happen to it in the long term. Species need to change to survive, but it seemed likely that the minimal cell would have trouble evolving.
“Every single gene in its genome is essential,” says Lennon. “The cell has zero degrees of freedom.” As a result, any mutations that arise would be expected to be harmful.
Lennon’s team began by establishing that the minimal cell could still mutate. It does so to such a degree that, even given a small population size of just 10 million, every single genetic “letter” would be expected to mutate more than 250 times over 2000 generations.
The team then grew .⳦Ǿ JCVI-syn3B in the lab, allowing them to evolve freely for 300 days.
Next, the team set up some head-to-head contests. In some experiments, the minimal cells that had evolved for 300 days were pitted against the original, non-minimal .⳦Ǿ. In others, the non-minimal cells went up against minimal cells that hadn’t evolved for 300 days.
In all contests, the team put equal quantities of the strains being assessed in a container and observed which one became more common, a sign of which was better suited to its environment.
The unevolved minimal bacterium was “really sick”, says Lennon, and was easily outcompeted by the non-minimal version. But the version that had evolved for 300 days did much better, recovering 80 per cent of the lost fitness (bioRxiv, ).
Crucially, the team identified the genes that changed most during these evolution contests, says at the University of Illinois at Urbana-Champaign, who wasn’t involved in the study. Some have unknown functions. “You have to go and ask yourself, ‘What does that thing do?’ ” she says.