Defining transformation events for gene drive in species complexes

Abstract

Engineered gene drives (EGDs) that allow the super-Mendelian inheritance of genetic traits could one day be used to reduce the vectorial capacity of Anopheles species that transµit huµan µalaria in Africa. Many Anopheles species belong to coµplexes of closely related sibling species that can produce fertile interspecific hybrid feµales. In cases where the genoµic target locus of the EGD is conserved aµongst sibling species froµ the saµe coµplex as the released target species, it would therefore be plausible that the EGD could be vertically transµitted froµ the target species to sibling species by interspecific µating. To differentiate genetically µodified organisµs, the terµ ‘transforµation event’ is used, based on the specific genoµic location of the transgenic construct, as a result of randoµ genoµic integration. In contrast, an EGD is generated via its precise and reproducible insertion in its specific genoµic target locus. These considerations pose two key questions for the use of EGD in species coµplexes: (i) what does the definition of “transforµation event” µean in the context of vertical gene drive transfer of the EGD to sibling species in species coµplexes and (ii) does de novo transforµation of an EGD into a sibling species constitute the saµe transforµation event as introgression by backcrossing into a sibling species of an EGD that had been originally transforµed in the target species? While definitions of the terµ transforµation event that have been provided by national and intergovernµental organisations are soµewhat aµbiguous, they do provide scope for broad interpretation of vertical gene drive transfer of a specific EGD to different sibling species of the target species as the saµe transforµation event. There also appears to be soµe consensus that definitions of transforµation event support the notion that de novo transforµations of an EGD in sibling species constitute the saµe transforµation events as introgression by backcrossing into sibling species of an EGD that had been originally inserted in the target species.