HOW GENE DRIVES SPREAD HOW GENE DRIVE WORKS Introduced endonuclease gene (aka the gene drive) Recognition site Homologous chromosomes Without gene drive, an allele will be passed from generation to generation via traditional Mendelian genetics. That is, when a heterozygous individual carrying only one copy of the allele mates with an individual lacking it altogether, only half of their offspring will inherit the genetic segment. But in a gene drive that spreads the allele to the homologous chromosome in the germline, all progeny will receive a copy. With gene drive, it’s even possible for a deleterious allele to spread though the population, despite imposing a severe fitness cost. With genetic modification WITHOUT GENE DRIVE Wild Type For years, researchers have looked to genetically modify mosquitoes to prevent the spread of malaria. But while introducing genetic changes has long been supported by advancing technologies, getting those modifications to spread through wild mosquito populations has remained a challenge. Now, the newly understood concept of gene drive, in which genetic elements can spread more rapidly than those following traditional Mendelian inheritance principles, may finally solve the problem. 1.0 Frequency Homing endonuclease recognizes and cuts a target sequence in the wild-type chromosome that is identical to the insertion site for its gene in the homologous chromosome. 0.5 0.0 0 10 20 30 Generations If the genetic modification has no negative fitness consequences, its frequency in the population will remain at whatever the initial introduced frequency was. The cell’s DNA repair machinery then uses the engineered chromosome of the homologous pair, which contains the endonuclease gene, as a template to rewrite the broken piece of chromosome. WITH GENE DRIVE 1.0 Frequency USING GENE DRIVE TO CONTROL MALARIA Researchers can also use promoter sequences to ensure the endonuclease’s expression in the germline, promoting its inheritance among offspring. Germline promoter 0.5 0.0 0 10 20 30 Generations With gene drive, the genetic modification will quickly increase in frequency until it is carried by all mosquitoes in the population.
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