Additive method: Synthesize genomes with the genes you expect to be necessary, pretty much an optimization problem on the number of genes where you continually

Additive method: Synthesize genomes with the genes you expect to be necessary, pretty much an optimization problem on the number of genes where you continually try to remove genes that were in previous iterations. Subtraction method: After reading a bit of the paper, they utilized Tn5, which causes a DNA sequence to be arbitrarily inserted into the DNA (Random locations). This randomly disrupts genes, causing them to likely not function correctly. Here's the logic: If all genes were necessary we would expect no cells to live that had mutations. If no genes were necessary we would expect all cells to have mutations at about an equal rate relative to the space they occupy. (Assuming no bias by the Tn5, but that's a nuance) What they instead found was that some cells grew, but there were certain genes that were not mutated, meaning that they are likely necessary. They also classified a few things like studying the growth of the cell (Slow growing, but still viable was classified as "quasi-essential") and implanting their minimal genome in another species, which failed giving evidence that a subset of genes that are sufficient for survival are not necessarily sufficient in all cells.