This cost arises because in each generation X-linked non-Medeaalleles present in heterozygousMedeafemale parents have a 50% probability of ending up in a male progeny, which are doomed to death because they cannot be rescued by a paternally derivedMedeaallele. results suggest thatMedeaelements can drive population replacement under a wide range of conditions. Keywords:population replacement, mosquito, maternal effect, introgression, dengue, malaria == Introduction == Mosquitoes are vectors for a number of important human diseases, including malaria and dengue fever. Replacement of insect disease vectors with modified counterparts refractory to pathogen transmission is a long-established concept for disease prevention (reviewed inBraig and Yan 2001;Gould and Schliekelman 2004;Sinkins and Gould 2006), and genes that inhibit the mosquito’s ability to transmitPlasmodiumor dengue have been identified (de Lara Capurro et al. 2000;Ito et al. 2002;Moreira et al. 2002;Franz et al. 2006;Corby-Harris, et al. 2010). However, the expression of these genes is not expected to result in a fitness benefit to carriers (Schmid-Hempel 2005;Tripet et al. 2008), and a large percentage of the wild population will need to be refractory in order to achieve substantial levels of disease control (Boete and Koella 2002). Therefore, effective population replacement is generally thought to require that genes conferring disease refractoriness be coupled with a mechanism, such as linkage with a selfish genetic element, for driving them through the wild population (Braig and Yan 2001;Gould and Schliekelman 2004;Sinkins and Gould 2006). Maternal-effect lethal selfish genetic elements were first described in the flour beetleTribolium castaneumand are known by the acronymMedea(maternal-effect dominant embryonic arrest).Tribolium Medea, which sits at a fixed chromosomal position, has the feature that when present in females, only progeny that inherit the element-containing chromosome survive (Beeman et al. 1992). In contrast, heterozygousMedea-bearing males give rise to wildtype andMedea-bearing progeny with equal frequency when mated to wildtype females. Therefore,Medeaenhances its transmission relative to competing non-Medea-bearing homologous chromosomes (hereafter referred to as the non-Medeaallele) by causing the death of progeny that do not carry a copy ofMedeafound in the mother. SyntheticMedeaelements have been generated that drive population replacement inDrosophila(Chenet al.2007). Medea’s ability to spread relies on the elimination from the population of non-Medeaalleles in the offspring of heterozygous females mated with non-Medeaor m-Tyramine hydrobromide heterozygous males. Selection against the non-Medeaallele is weak at low and highMedeaallele frequencies, when such crosses are rare. Therefore, if there is selection against theMedeaallele (carriers experience a cost), this process produces a threshold frequency (an unstable equilibrium), below whichMedeawill be lost, and above whichMedeawill spread to a stable equilibrium.Wade and Beeman (1994)showed that if the presence ofMedeadoes not result in a fitness (fecundity) cost to carriers,Medeaspreads to fixation for all degrees of maternal effect lethality, though the rate ofMedeaincrease is initially very slow. They also showed that if the presence ofMedearesults in a decrease in fecundity independent of maternal-effect killing, the frequency of theMedeaallele could still increase to a stable internal equilibrium provided that fitness costs were recessive, or if dominant, small. These authors, and Smith (Smith 1998), showed thatMedea’s ability to spread in the face of fitness costs could be enhanced if progeny of aMedea-bearing mother compete with each other for resources. In this context, known as family-level, or soft selection (Wade, 1985;Kelly 1992), the death of non-Medeaoffspring within the family of aMedea-bearing mother frees limited resources for siblingMedea-bearing progeny. In the work below we assume no family-level selection because this assumption provides a more conservative estimate ofMedea’s potential as a population replacement drive mechanism. That said, some mosquitoes, such asAedes aegypti, an important vector of dengue, breed in small containers that may often be resource-limited for larval growth (Clements 1999), suggesting that family-level selection could be important in some contexts, a topic that should be further explored. Population genetic models ofHastings (1994),Smith (1998)andChen et al. (2007)show that, in the absence of family-level selection,Medeaelements with significant dominant fitness costs can still spread, provided they are introduced above a critical introduction frequency. Previous work has focused on the fate of theMedeaallele. However, it is the fate ofMedea-bearing genotypes that is important for population replacement.Chen et al. (2007)showed that, at least under some conditions, whenMedeaelements m-Tyramine hydrobromide with fitness costs are m-Tyramine hydrobromide introduced at frequencies that result in spread to an internal Rabbit Polyclonal to IKK-alpha/beta (phospho-Ser176/177) equilibrium allele frequency, non-Medeaindividuals are nonetheless rapidly eliminated from.