Synthetic Evolution: Genetically Minimal Artificial Cells Demonstrate the Resilience of Life

Evolutionary biologist Jay T. Lennon and his research team have delved into the realm of synthetic minimal cells by removing 45% of their genes, reducing them to the most essential set required for self-sustaining life. Surprisingly, despite this reduction, the minimal cells evolved at a comparable pace to regular cells, revealing the inherent resilience of life.

The study revealed that synthetic cells with minimized genomes could undergo rapid evolution, even after losing a substantial portion of their original genes. The laboratory experiment, spanning 300 days, demonstrated that evolution persists even under perceived limitations.

In the words of Ian Malcolm, portrayed by Jeff Goldblum in the 1993 science fiction film 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 finds a way.”

While evolutionary biologist Jay T. Lennon’s laboratory may not harbor any lurking Velociraptors, his research has conclusively shown that life indeed finds a way. Lennon, a professor in the Department of Biology at Indiana University Bloomington, and his colleagues have been studying minimal cells constructed synthetically, with only the essential genes remaining. Remarkably, these streamlined cells can undergo evolution at a pace equivalent to normal cells, showcasing the adaptability of organisms, even with seemingly inflexible genomes.

The research team utilized a synthetic organism called Mycoplasma mycoides JCVI-syn3B, a minimized version of the bacterium M. mycoides found in the digestive systems of goats and similar animals. Over time, the parasitic bacterium naturally shed many of its genes as it evolved to rely on its host for sustenance. Researchers at the J. Craig Venter Institute took this process further by eliminating 45% of the 901 genes from the natural M. mycoides genome in 2016, resulting in the smallest set of genes required for independent cellular life. With only 493 genes, the minimal genome of M. mycoides JCVI-syn3B is the smallest among all known free-living organisms. In contrast, animal and plant genomes often contain over 20,000 genes.

The concept of the simplest organism entails no functional redundancies, possessing only the minimal number of genes necessary for life. However, any mutation in such an organism could lethally disrupt one or more cellular functions, imposing constraints on evolution. Organisms with streamlined genomes present fewer targets for positive selection, thus limiting opportunities for adaptation.

Despite these potential limitations, M. mycoides JCVI-syn3B exhibited an exceptionally high mutation rate. The researchers allowed the synthetic cell to evolve freely for 300 days in a laboratory environment, equivalent to 2000 bacterial generations or roughly 40,000 years of human evolution.

Subsequently, the team conducted experiments to compare the performance of the minimal cells that had evolved for 300 days with the original non-minimal M. mycoides and a strain of minimal cells that had not undergone evolution for 300 days. In these tests, equal amounts of the strains were placed together in a test tube, with the strain best suited to its environment becoming the dominant one.

The results showed that the non-minimal version of the bacterium easily outcompeted the unevolved minimal version. However, the minimal bacterium that had undergone 300 days of evolution fared significantly better, recovering all the fitness it had lost due to genome streamlining. The researchers identified the genes that underwent the most changes during evolution, including some involved in cell surface construction, while the functions of several others remained unknown.

The findings of this study were published in the journal Nature and hold implications for various biological fields, such as the treatment of clinical pathogens, the persistence of host-associated endosymbionts, the refinement of engineered microorganisms, and even the origins of life itself. Lennon and his team’s research exemplifies the ability of natural selection to rapidly optimize the fitness of the simplest autonomous organisms, shedding light on the evolution of cellular complexity and reinforcing the idea that life will always find a way.

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More about synthetic minimal cells

• Nature: Evolution of a minimal cell
• Indiana University Bloomington: Jay T. Lennon
• J. Craig Venter Institute: Synthetic Biology
• National Center for Imaging and Microscopy Research at UC San Diego
• Jurassic Park (1993 film)