Engineered reproductively isolated species drive reversible population replacement

Abstract

Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. Here, to overcome this challenge, we engineer SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species), an engineered genetic incompatibility approach, to generate postzygotic reproductive barriers. Using this approach, we create multiple reproductively isolated SPECIES and demonstrate their reproductive isolation and threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

“…Engineered Genetic Incompatibility (EGI) is a strategy for creating bi-directional (male-to-female and female-to-male) mating incompatibility that mirrors the behavior of post-zygotic speciation mechanisms. ( Maselko et al, 2020 ; Maselko et al, 2017 ; Buchman et al, 2021 ; Waters et al, 2018 ). We created EGI lines by engineering flies to express a dCas9-based programmable transcription activator (PTA) that targets the promoter of a gene which is lethal with expressed too high or in the tissues.…”

“…As with other underdominant biocontrol methods, EGI could be used as a threshold-dependent gene drive ( Magori and Gould, 2006 ; Davis et al, 2001 ; Buchman et al, 2021 ). Alternatively, it could be coupled to a conditional female-lethal construct, such as the tetracycline (Tet)-repressible positive feedback circuit ( Fu et al, 2007 ; Li et al, 2014 ), to produce a strain that more closely replicates SIT biocontrol agents.…”

Genetically engineered insects with sex-selection and genetic incompatibility enable population suppression

“…Several new techniques for genetic biocontrol have been shown effective in proof-of-concept experiments (13,15,19,(25)(26)(27)(28)(29)(30). Combination approaches that bring together two or more distinct techniques can exhibit synergistic behaviors that are attractive for genetic biocontrol applications.…”

“…creating bi-directional (male-to-female and female-to-male) mating incompatibility that mirrors the behavior (13)(14)(15)(16). EGI strains are homozygous for haplosufficient lethal genes with haploinsufficient resistance genes.…”

“…As with other underdominant biocontrol methods, EGI could be used as a threshold-dependent gene drive (15,17,18). Alternatively, it could be coupled to a conditional femalelethal construct, such as the tetracycline (Tet)-repressible positive feedback circuit (19)(20)(21), to produce a strain that more closely replicates SIT biocontrol agents.…”