title: General principles of single-construct chromosomal gene drive.
abstract: Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of offspring arising from specific parental crosses unviable. Under permissive conditions, a number of these elements are capable of distorting the offspring ratio in their favor. We use a population genetic framework to derive conditions under which these elements spread to fixation in a population or induce a population crash. Many of these systems can be engineered using combinations of toxin and antidote genes, analogous to Medea, which consists of a maternal toxin and zygotic antidote. The majority of toxin-antidote drive systems require a critical frequency to be exceeded before they spread into a population. Of particular interest, a Z-linked Medea construct with a recessive antidote is expected to induce an all-male population crash for release frequencies above 50%. We suggest molecular tools that may be used to build these systems, and discuss their relevance to the control of a variety of insect pest species, including mosquito vectors of diseases such as malaria and dengue fever.
authors: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. john.marshall@imperial.ac.uk
authors: John M
authors: JM
authors: Marshall
authors: Bruce A
authors: BA
authors: Hay
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D000931:Antidotes / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D009033:Culicidae / Q000235:genetics / Q000378:metabolism; D005260:Female; D051456:Gene Flow; D056084:Genetic Fitness; D007303:Insect Vectors / Q000235:genetics / Q000378:metabolism; D007313:Insecta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D010571:Pest Control; D011157:Population Dynamics; D012730:Sex Chromosomes / Q000235:genetics / Q000378:metabolism; D014118:Toxins, Biological / Q000235:genetics / Q000378:metabolism
chemical_list: D000931:Antidotes; D014118:Toxins, Biological