First Steps towards Underdominant Genetic Transformation of Insect Populations

<div><p>The idea of introducing genetic modifications into wild populations of insects to stop them from spreading diseases is more than 40 years old. Synthetic disease refractory genes have been successfully generated for mosquito vectors of dengue fever and human malaria. Equally important is the development of population transformation systems to drive and maintain disease refractory genes at high frequency in populations. We demonstrate an underdominant population transformation system in <i>Drosophila melanogaster</i> that has the property of being both spatially self-limiting and reversible to the original genetic state. Both population transformation and its reversal can be largely achieved within as few as 5 generations. The described genetic construct {<i>Ud</i>} is composed of two genes; (1) a <i>UAS-RpL14.dsRNA</i> targeting RNAi to a haploinsufficient gene <i>RpL14</i> and (2) an RNAi insensitive <i>RpL14</i> rescue. In this proof-of-principle system the <i>UAS-RpL14.dsRNA</i> knock-down gene is placed under the control of an <i>Actin5c-GAL4</i> driver located on a different chromosome to the {<i>Ud</i>} insert. This configuration would not be effective in wild populations without incorporating the <i>Actin5c-GAL4</i> driver as part of the {<i>Ud</i>} construct (or replacing the UAS promoter with an appropriate direct promoter). It is however anticipated that the approach that underlies this underdominant system could potentially be applied to a number of species.</p>