Observing the gradual transition from life to non-life tells us a lot about the features of living systems. Based on this idea, we started simplifying natural cells by inactivating their genes randomly through experimental evolution. Escherichia coli (E. coli) cells were cultured in a high-mutagenicity environment to accumulate replication errors on their genomes. As a result, we observed dozens of mutations, which were supposed to deactivate gene expression. In addition, the gene inactivation accumulates time proportionally without growth defects so far. These results suggest that naturally isolated cells are highly redundant in an experimental environmentimplying the possibility of further simplification deleting hundreds or thousands of genes.