title: Modeling the Manipulation of Natural Populations by the Mutagenic Chain Reaction.
abstract: 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 near equivalence of this system to other gene drive models and review the results of simple models showing that, when there is a fitness cost to the MCR allele, an internal equilibrium may exist that is usually unstable. In this case, introductions must be at a frequency above this critical point for the successful invasion of the MCR allele. We obtain estimates of fixation and invasion probabilities for the appropriate scenarios. Finally, we discuss how polymorphism in natural populations may introduce sources of natural resistance to MCR invasion. These modeling results have important implications for application of MCR in natural populations.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853 unckless@cornell.edu.
authors.forename: Robert L
authors.identifier: http://orcid.org/0000-0001-8586-7137
authors.initials: RL
authors.lastname: Unckless
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Philipp W
authors.identifier: http://orcid.org/0000-0001-8453-9377
authors.initials: PW
authors.lastname: Messer
authors.affiliation: School of Biological Sciences, Monash University, Clayton, 3800 Victoria, Australia.
authors.forename: Tim
authors.identifier: http://orcid.org/0000-0002-1962-4951
authors.initials: T
authors.lastname: Connallon
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
mesh_terms: D000483:Alleles; D064113:CRISPR-Cas Systems / Q000235:genetics*; D005828:Genetics, Population; D008962:Models, Theoretical; D009154:Mutation / Q000235:genetics; D012641:Selection, Genetic
keywords: CRISPR/Cas9; gene drive; mutagenic chain reaction; whole population replacement