Artificial cells prove that life finds its way

“Listen, if the history of evolution has taught us anything, it’s that life doesn’t stop. Life is released. It expands into new territories and hits barriers painfully, perhaps even dangerously, but… life finds a way,” said Dr Ian Malcolm in Jurassic Parkthe 1993 movie about a park with live dinosaurs.

You won’t find any velociraptor hanging around the evolutionary biologist’s lab Jay T Lennon by the College of Arts and Sciences at the University of Indiana Bloomington (USA), but this researcher and his colleagues discovered that life has a way.

A simplified cell, with a minimal genome that apparently offers little flexibility, can evolve as quickly as a normal one.

Your team has been studying a artificial or minimal cellsynthetically constructed, stripped of all but the most essential genes.

The results, published in the journal Naturereveal that this simplified cell can evolve as quickly as a normal one, demonstrating the adaptability of organisms, even with an unnatural genome that apparently offers little flexibility.

“There seems to be something in life that is really robust,” says Lennon, “we can simplify it down to the essentials, but that doesn’t stop evolution from working.”

Specifically, Lennon’s team used the synthetic organism Mycoplasma mycoides JCVI-syn3Ba minified version of the bacteria M. mycoides which is usually found in the intestines of goats and similar animals. Over the millennia, this parasitic bacteria naturally lost many of its genes as it evolved to depend on its host for food, but in 2016 researchers at the J. Craig Venter Institute from California went a step further.

Minimal genome with 493 genes

At the time, they removed 45% of the 901 genes from the natural genome of this bacterium, reducing it to the smallest set of genes necessary for autonomous cell life. With 493 genesthe minimal genome of M. mycoides JCVI-syn3B it is the smallest of all known free-living organisms and is the one Lennon’s team has already used. For comparison, many animal and plant genomes contain over 20,000 genes.

In principle, the simplest organism would have no functional redundancies and would have only the minimum number of genes essential for life. Any one of these mutations could lethally alter one or more cellular functions, which would limit evolution. Organisms with simplified genomes have fewer targets for selection, limiting opportunities for adaptation.

The researchers found that the synthetic bacteria had an exceptionally high mutation rate.

Although M. mycoides JCVI-syn3B could grow and divide under laboratory conditions, Lennon and his colleagues wanted to know how a small cell would respond to forces of evolution over timeabove all, taking into account the limited raw material on which natural selection could act, as well as the emergence of new mutations.

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“Each individual gene in your genome is essential,” says Lennon, referring to M. mycoides JCVI-syn3B, “and it can be assumed that there is no room for maneuver for mutations, which could limit their evolutionary potential.” However, the researchers discovered that this synthetic bacteria does, in fact, have an exceptionally high mutation rate.

Like 40,000 years of human evolution

With that information, the scientists grew it in the lab, where it was allowed to evolve freely for 300 dayswhich is equivalent to 2,000 bacterial generations or about 40,000 years of human evolution.

They then performed experiments to determine how the tiny cells that had evolved for 300 days fared compared to the M. mycoides non-minimal original strain and with minimal cell strain that did not evolve for 300 days.

The tiny bacterium that evolved for 300 days fared much better, regaining all the biological fitness it had lost due to genome rationalization.

In comparative tests, the researchers placed equal amounts of the tested strains in a test tube. The one that best adapted to its environment became the most common strain.

They found that the non-minimal version of the bacteria easily outperformed the minimal unevolved version. However, the tiny bacterium that evolved for 300 days fared much better, regaining all the biological fitness it had lost due to genome rationalization.

Genes to build the cell wall

The researchers identified the genes that changed the most during evolution. some of those genes were involved in cell surface constructionwhile the functions of several others remain unknown.

Understanding how organisms with simplified genomes overcome evolutionary challenges has important implications for biological problems.

Understanding how organisms with simplified genomes overcome evolutionary challenges has important implications for biological problems such as the treatment of clinical pathogens, the persistence of endosymbionts (they live inside others), the refinement of artificial microorganisms, and the origin of life itself.

Research by Lennon and his team shows the power of natural selection to rapidly optimize biological fitness in the simplest autonomous organism, with implications for the evolution of cellular complexity. In other words, it shows that life has a way of moving forward.

Reference:

RZ Moger-Reischer, JT Lennon et al. “Evolution of a minimal cell”. Nature2023.

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