The minimal cell and how it evolved

Researchers conducted a groundbreaking study on a bacterium with a minimal genome. They observed that despite a loss of fitness during genome minimisation, the minimal cell evolved and regained its lost fitness over 2,000 generations. The study revealed that evolution persisted even in the absence of backup genes, challenging previous assumptions. These findings have significant implications for understanding the adaptability of organisms with simplified genomes and their relevance to clinical pathogens, host-associated endosymbionts, engineered microorganisms, and the origins of life itself.
The minimal genome has been created and it evolves
Researchers created a bacterium with a minimal genome and when allowed to divide and grow for many generations, it evolved.


  1. Minimal genome: A small set of essential genes for organism survival.
  2. Mycoplasma mycoides JCVI-syn3B: Bacterium with the smallest known free-living organism’s minimal genome (493 genes).
  3. Fitness loss: Engineering the minimal cell caused a 57% decrease in fitness compared to non-minimal cells.
  4. Evolution experiment: The minimal cell underwent 2,000 generations, providing a unique model for studying evolution.
  5. Evolutionary observations: The minimal cell evolved and regained lost fitness, except for cell size due to gene mutations.
  6. Genome constraints: Scientists originally expected minimal genomes to be limited in evolution, but the study showed that evolution persists even with essential genes.
  7. Implications: Understanding minimal genomes helps address clinical pathogen treatment, host-associated endosymbionts, engineered microorganisms, and the origin of life.

John Craig Venter, the American biologist known for his role in sequencing the human genome, was also involved in another remarkable feat. His team of researchers engineered the first bacterium with a minimal genome 123.

A minimal genome refers to the smallest set of genes or genetic material necessary for an organism to survive and carry out essential functions. It typically consists of the core genes required for basic cellular processes and minimal biological functionality.

Venter’s group first created a minimal synthetic organism, Mycoplasma mycoides JCVI-syn1.0 in 2010. Six years later, they streamlined the genome of this bacterium to generate the cell with an absolute minimum genome, Mycoplasma mycoides JCVI-syn3b. At just 493 genes, the minimal genome of M. mycoides JCVI-syn3B is the smallest of any known free-living organism. In comparison, the human genome contains around 20,000 genes.

Now, another group of researchers, led by Jay Lennon, studied this minimal bacterium.

They first estimated that the process of engineering this minimal cell resulted in a 57% loss of fitness compared to non-minimal cells 4.

They then allowed the minimal cell to divide for 2000 generations. The minimal cell, generated from M. mycoides divides every 16 hours or so. Therefore, 2000 generations would be completed in just a few years. In contrast, humans would need tens of thousands of years to complete 2000 generations. This makes this simple bacterial cell with a minimal genome an excellent model system to study evolution over a large number of generations.

What the researchers observed during and after the minimal cell divided for 2000 generations is simply mind-boggling.

Evolution is fundamental

The minimal cell evolved generation after generation. With this evolution, it regained its lost fitness.

The minimal cells evolved faster than non-minimal cells, except in terms of cell size, which remained constant for minimal cells due to mutations in ftsZ, a gene regulating cell division and morphology.

This indicated to the scientists that evolution is a fundamental process of nature. As long as there is a genome and if it can divide and replicate, evolution will act on it, constantly selecting for increased fitness.

Scientists originally thought that minimal genomes would succumb more to mutations due to the lack of backup genes. They hypothesised that the forces of evolution driven by mutations would be constrained due to this deficiency.

However, results from the Lennon group strikingly suggest that evolution will not stop, even when constrained.

“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.”

Why minimise genomes?

Studying how organisms with simpler genomes tackle evolutionary challenges is crucial for addressing various important biological issues.

For instance, finding effective treatments for clinical pathogens requires understanding the essential genes of these pathogens and how they adapt over generations.

Similarly, understanding how host-associated endosymbionts (microbes living inside us) persist will help us understand their relationship with our bodies.

Understanding how genomes evolve will also inform our researchers on improving engineered microorganisms and genetic engineering in general. Moreover, it will help unravel the origins of life.

The recent research conducted by Lennon and his team sheds light on the remarkable ability of natural selection to rapidly enhance fitness in the most basic self-sufficient organisms. This finding carries significant implications for understanding how cellular complexity evolves. In simpler terms, it shows that life has an incredible knack for adapting and surviving in the face of challenges.


  1. Claire M. Fraser et al., The Minimal Gene Complement of Mycoplasma genitalium. Science. 270, 397-404 (1995).
  2. Daniel G. Gibson et al., Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science. 329, 52-56 (2010).
  3. Clyde A. Hutchison et al., Design and synthesis of a minimal bacterial genome. Science. 351, (2016).
  4. R. Z. Moger-Reischer et al., Evolution of a minimal cell. Nature. (2023).
Photo of Sampath Amitash Gadi, author at
Sampath AmitashGadi, Ph.D.
Editor at

Sampath works as a DNA researcher at the University of Copenhagen. Right now, he is studying how proteins and protein signaling help with DNA Damage in cells.

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