Researchers stripped half of this artificial cell’s genome to prove, as they say in Jurassic Park, “life finds a way”

A synthetically constructed “minimal cell” which has been stripped of all but its essential genes has done something it shouldn’t have been able to – it evolved just as fast as a normal cell.

A study published in Nature demonstrates the capacity for organisms to adapt, even when their genome has been artificially altered to provide very little flexibility.

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It recalls the refrain of Dr Ian Malcolm, fictional character and one of the main protagonists in Steven Spielberg’s 1993 classic Jurassic Park:

Listen, if there’s one thing the history of evolution has taught us is that life will not be contained. Life breaks free. It expands to new territories and it crashes through barriers painfully, maybe even dangerously, but… life, uh, finds a way.

“It appears there’s something about life that’s really robust,” says senior author and professor of evolutionary biology Jay T. Lennon at Indiana University Bloomington. “We can simplify it down to just the bare essentials, but that doesn’t stop evolution from going to work.”

Green structure of smaller balls electron micrograph cells on blue background
Electron micrograph of a cluster of minimal cells magnified 15,000 times. Credit: Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy Research at the University of California at San Diego.

Lennon’s team used the synthetic organism Mycoplasma mycoides JCVI-syn3B for their study. The genetically engineered organism is a “minimised” version of the bacterium Mycoplasma mycoides which is commonly found in the guts of goats and similar animals.

In 2016, researchers at California’s J. Craig Venter Institute eliminated 45% of the 901 genes from the natural M. mycoides genome, reducing the organism to the smallest number of genes required for autonomous cellular life. This took to the extreme a process that has naturally been underway in the evolution of M. mycoides which has naturally lost many genes, depending on its host for nutrition.

With only 493 genes, the artificial genome of M. mycoides JCVI-syn3B is the smallest of any known free-living organism. Most animals and plants have more than 20,000 in their genomes.

Theoretically, this minimal genome would mean that any mutation could lethally disrupt one or more cellular function, placing extreme constraints on the organism’s evolution.

M. mycoides JCVI-syn3B could grow and divide in the lab. “Every single gene in its genome is essential,” Lennon says. “One could hypothesise that there is no wiggle room for mutations, which could constrain its potential to evolve.” So, they put this hypothesis to the test.

What they found was the opposite – M. mycoides JCVI-syn3B has an exceptionally high mutation rate.

Allowed to evolve freely for 300 days – about 2,000 bacterial generations, equivalent to approximately 40,000 years of human evolution – the researchers found that M. mycoides JCVI-syn3B was able to adapt about as quickly as the non-minimal natural version of M. mycoides to environmental strain.

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The researchers were able to pinpoint the specific genes which mutated during the minimal organism’s evolution. Some are involved in constructing the surface of the cell, while others’ function is unknown.

Understanding such extremes has important implications including treating pathogens, refining engineered microorganisms and revealing the mysteries of the origin of life itself.

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