Abstract
Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Here, we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. EGI couples a dominant lethal transgene with a recessive resistance allele. Strains homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. EGI genotypes can also be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. EGI is a simple and robust approach in multiple sexually reproducing organisms.
Highlights
Speciation constrains the flow of genetic information between populations of sexually reproducing organisms
We observed unique hybrid incompatibility phenotypes that depended on the combination of programmable transcription activators (PTAs) and sgRNA used to drive over or ectopic expression
We employed the engineered genetic incompatibilities (EGIs) approach that was recently described in yeast[9]
Summary
The second method involved re-injecting embryos from homozygous promoter mutant strains with a single plasmid containing expression constructs for both the dCas9-VPR and the sgRNA (Fig. 3b bottom). The latter approach was more direct, requiring approximately half the number of crosses, but resulted in a different chromosomal location for PTA expression constructs compared to what was previously characterized EGI strains that drove over or ectopic expression of wingless or pyramus both showed full incompatibility, with no hybrids surviving to adulthood (Fig. 3c). Activation of hedgehog produced a later-acting lethal phenotype compared to activation of pyramus and wingless in the a wg promoter
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