The universal X-shredder: Enabling genetic control by sex ratio distortion in agricultural pests and disease vectors

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Insects transmit a great number of diseases to humans, animals and plants. They also directly feed on agricultural plants, reducing agricultural production and causing empty stomachs for the poorest and huge economic losses for farmers. The world's climate is changing allowing insects to invade new regions and reproduce faster. A growing human population puts a rising strain on the worlds agricultural systems while at the same time insects are becoming increasingly resistant to our most powerful weapon - insecticides. The global burden insects pose on human health and society is therefore expected to increase. These challenges are forcing us to envision novel ways in which we can sustainably control insects.Genetic control of insects is a form of biological control where the release of modified insects reduces or eliminates the potential of wild insect populations to do harm. For example the mass-release of sterilized males has been used to reduce the population size of many insect pests for many decades.One such genetic control strategy is to strongly bias the sex ratio of a population towards males so that the population, due to a lack of females, decreases in size or is eliminated altogether. Normally half of a male's sperm carry the Y-chromosome and go on to make males whereas the other half carries the X chromosome and go on to make females. A gene that biases the production of sperm towards those that carry the Y-chromosome is refereed to as a sex ratio distorter. We have, for the first time, generated such a distorter gene which destroys the X-chromosome by cutting its DNA in many places and successfully tested it in the malaria mosquito. The biology of the mosquito allowed us take a shortcut, as "molecular scissors" that could cut the DNA of the mosquito's X-chromosome were already available and could be used with little modification.In this project we want to explore whether similar distorter genes can also be created for many other insect pest or vector species and to destroy their respective X-chromosomes. First we will develop a bioinformatic algorithm that is able to identify, using DNA sequences from male and female insects, positions where the X-chromosome can be cut. We will then use the novel CRISPR "molecular scissor" technology to cut the X-chromosome when sperm are made and study the effect on the progeny. If it works and only sperm carrying the Y survive we will find that these insects now produce mostly male offspring.We will first test this approach in the fruit fly Drosophila, as the fly is a genetic powerhouse allowing many genetic experiments to be concluded quickly and efficiently. If successful we will then test this technology in one well studied insect pest species for example Ceratitis capitata, the Mediterranean fruit fly capable of damaging many fruit crops. We will show that male flies carrying the distorter gene when placed in a cage with a population of normal flies will reduce that population or even eliminate it.If it works our control strategy can in the future be applied to protect food crops from insect pests or humans and animals from insect-borne diseases.