GENETICS | INVESTIGATION Theoretical consequences of the Mutagenic Chain Reaction for manipulating natural populations

ABTRACT The use of recombinant genetic technologies for population manipulation has mostly remained an abstract idea due to the lack of a suitable means to drive novel gene constructs to high frequency in populations. Recently Gantz and Bier showed that the use of CRISPR/Cas9 technology could provide an artificial drive mechanism, the so-called Mutagenic Chain Reaction (MCR), which could lead to rapid fixation of even a deleterious introduced allele. We establish the equivalence of this system to models of meiotic drive and review the results of simple models showing that, when there is a fitness cost to the MCR allele, an internal equilibrium exists that is usually unstable. Introductions must be at a frequency above this critical point for the successful invasion of the MCR allele. These modeling results have important implications for application of MCR in natural populations.