Genetisch minimale künstliche Zellen beweisen: „Das Leben findet einen Weg“

Der Evolutionsbiologe Jay T. Lennon und sein Team haben eine synthetische Minimalzelle untersucht, bei der 45 % der Gene entfernt wurden, wodurch sie auf den kleinsten Satz an Genen reduziert wurde, der für autonomes Leben erforderlich ist. Trotz ihres reduzierten Genoms stellte Lennons Team fest, dass sich diese minimale Zelle genauso schnell entwickelte wie eine normale Zelle, was die dem Leben innewohnende Widerstandsfähigkeit zeigt.

Wissenschaftler haben herausgefunden, dass sich eine synthetische Zelle mit einem reduzierten Genom genauso schnell entwickeln kann wie eine normale Zelle. Obwohl die Zelle 45 % ihrer ursprünglichen Gene verlor, passte sie sich an und demonstrierte in einem 300-tägigen Laborexperiment ihre Widerstandsfähigkeit, was eindrucksvoll bewies, dass Evolution auch unter vermeintlichen Einschränkungen stattfindet.

„Hören Sie, wenn uns die Geschichte der Evolution eines gelehrt hat, dann ist das, dass das Leben nicht eingedämmt werden kann. Das Leben bricht aus. Es dehnt sich in neue Gebiete aus und bricht schmerzhaft, vielleicht sogar gefährlich, durch Barrieren, aber … . . Das Leben findet einen Weg“, sagte Ian Malcolm, Jeff Goldblums Figur in

You won’t find any Velociraptors lurking around evolutionary biologist Jay T. Lennon’s lab; however, Lennon, a professor in the College of Arts and Sciences Department of Biology at Indiana University Bloomington, and his colleagues have found that life does indeed find a way. Lennon’s research team has been studying a synthetically constructed minimal cell that has been stripped of all but its essential genes. The team found that the streamlined cell can evolve just as fast as a normal cell—demonstrating the capacity for organisms to adapt, even with an unnatural genome that would seemingly provide little flexibility.

Cluster of Minimal Cells Electron Micrograph

Electron micrograph of a cluster of minimal cells magnified 15,000 times. The synthetically streamlined bacterium, Mycoplasma mycoides, contains less than 500 genes. Credit: Image by Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy Research at the University of California at San Diego

“It appears there’s something about life that’s really robust,” says Lennon. “We can simplify it down to just the bare essentials, but that doesn’t stop evolution from going to work.”

For their study, Lennon’s team used the synthetic organism, Mycoplasma mycoides JCVI-syn3B—a minimized version of the bacterium M. mycoides commonly found in the guts of goats and similar animals. Over millennia, the parasitic bacterium has naturally lost many of its genes as it evolved to depend on its host for nutrition. Researchers at the J. Craig Venter Institute in California took this one step further. In 2016, they eliminated 45 percent of the 901 genes from the natural M. mycoides genome—reducing it to the smallest set of genes required for autonomous cellular life. At 493 genes, the minimal genome of M. mycoides JCVI-syn3B is the smallest of any known free-living organism. In comparison, many animal and plant genomes contain more than 20,000 genes.

Minimal Cells Electron Micrograph

Electron micrograph of a cluster of minimal cells magnified 15,000 times. The synthetically streamlined bacterium, Mycoplasma mycoides, contains less than 500 genes. Credit: Image by Tom Deerinck and Mark Ellisman of the National Center for Imaging and Microscopy Research at the University of California at San Diego

In principle, the simplest organism would have no functional redundancies and possess only the minimum number of genes essential for life. Any mutation in such an organism could lethally disrupt one or more cellular functions, placing constraints on evolution. Organisms with streamlined genomes have fewer targets upon which positive selection can act, thus limiting opportunities for adaptation.

Jay Lennon

Jay T. Lennon. Credit: Photo by Indiana University

Although M. mycoides JCVI-syn3B could grow and divide in laboratory conditions, Lennon and colleagues wanted to know how a minimal cell would respond to the forces of evolution over time, particularly given the limited raw materials upon which natural selection could operate as well as the uncharacterized input of new mutations.

“Every single gene in its genome is essential,” says Lennon in reference to M. mycoides JCVI-syn3B. “One could hypothesize that there is no wiggle room for mutations, which could constrain its potential to evolve.”

The researchers established that M. mycoides JCVI-syn3B, in fact, has an exceptionally high mutation rate. They then grew it in the lab where it was allowed to evolve freely for 300 days, equivalent to 2000 bacterial generations or about 40,000 years of human evolution.

The next step was to set up experiments to determine how the minimal cells that had evolved for 300 days performed in comparison to the original, non-minimal M. mycoides as well as to a strain of minimal cells that hadn’t evolved for 300 days. In the comparison tests, the researchers put equal amounts of the strains being assessed together in a test tube. The strain better suited to its environment became the more common strain.

They found that the non-minimal version of the bacterium easily outcompeted the unevolved minimal version. The minimal bacterium that had evolved for 300 days, however, did much better, effectively recovering all of the fitness that it had lost due to genome streamlining. The researchers identified the genes that changed the most during evolution. Some of these genes were involved in constructing the surface of the cell, while the functions of several others remain unknown.

Details about the study can be found in a paper recently featured in the journal Nature.

Reference: “Evolution of a minimal cell” by R. Z. Moger-Reischer, J. I. Glass, K. S. Wise, L. Sun, D. M. C. Bittencourt, B. K. Lehmkuhl, D. R. Schoolmaster Jr, M. Lynch and J. T. Lennon, 5 July 2023, Nature.
DOI: 10.1038/s41586-023-06288-x

Roy Z. Moger-Reischer, a Ph.D. student in the Lennon lab at the time of the study, is first author on the paper.

Understanding how organisms with simplified genomes overcome evolutionary challenges has important implications for long-standing problems in biology—including the treatment of clinical pathogens, the persistence of host-associated endosymbionts, the refinement of engineered microorganisms, and the origin of life itself. The research done by Lennon and his team demonstrates the power of natural selection to rapidly optimize fitness in the simplest autonomous organism, with implications for the evolution of cellular complexity. In other words, it shows that life finds a way.


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