Applying evolution in the laboratory poses a fundamental problem: the experiments can take so long, researchers may turn gray waiting for results. The process rests on random mutations passed on during reproduction: beneficial mutations that improve fitness spread in subsequent generations, detrimental changes are pared. But even in fast-reproducing organisms, a round of laboratory evolution takes about a week. For “100 rounds of evolution, that’s two years,” says professor of chemistry and chemical biology David Liu. “If you need to do a thousand rounds, that’s two decades. It’s just not practical to set up experimental evolution on that time scale,” especially given the risk that an experiment might not work.
Viruses, which consist of genetic code in a protein capsule, reproduce by hijacking the machinery of cells. The virus and host combination at the heart of the PACE system (the acronym stands for phage-assisted continuous evolution) is filamentous bacteriophage, which infects E. coli cells. PACE forces the virus into a dependent relationship with the host cell. To engineer this dependency, researchers remove a piece of the viral genome critical to the virus’s survival and place it in the E. coli cell’s genome instead. Now the virus can’t survive unless the cell provides what it needs. At the same time, the researchers modify the host cell to produce what the virus needs only if the gene the researchers are forcing to evolve is increasingly active in the virus. What results is a biological machine for evolution that promotes the activity of the specific DNA sequence the researchers have introduced.
