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.
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.