Towards the genetic control of invasive species

Abstract

Invasive species remain one of the greatest threats to global biodiversity. Their control would be enhanced through the development of more effective and sustainable pest management strategies. Recently, a novel form of genetic pest management (GPM) has been developed in which the mating behaviour of insect pests is exploited to introduce genetically engineered DNA sequences into wild conspecific populations. These 'transgenes' work in one or more ways to reduce the damage caused by a particular pest, for example reducing its density, or its ability to vector disease. Although currently being developed for use against economically important insect pests, these technologies would be highly appropriate for application against invasive species that threaten biodiversity. Importantly, these technologies have begun to advance in scope beyond insects to vertebrates, which include some of the world's worst invasives. Here we review the current state of this rapidly progressing field and, using an established set of eradication criteria, discuss the characteristics which make GPM technologies suitable for application against invasive pests.

Keywords: Biodiversity conservation; Eradication; Genetic control; Genetic pest management; Invasive species; Refractory transgene; Transgenic control.

Fig. 1

Inheritance and effects of self-limiting population suppression strategies once released into target populations. Released individuals are transgene homozygous males (full red circle) which mate with wild-type females (full white circle), producing F₁ heterozygotes (red/white semicircle). A Bisex-lethal transgene: All F₁ individuals die. B Female-lethal: F₁ females die. F₁ males survive and pass on the transgene to 50% of their F₂ progeny; female F₂ transgene carriers also die. C Nuclease-based sex ratio distortion (SRD)—described in main text using HEGs. Nuclease expressed from transgene located on autosome. X-chromosomes are destroyed by action of the nuclease during meiosis so that transgenic males produce only Y-bearing sperm. All F₁ progeny are male and are transgene heterozygotes. Heterozygous males will pass the transgene to their (all male) F₂ progeny at Mendelian ratios. Note that the same design but with the nuclease transgene located on the Y-chromosome instead of an autosome provides a self-sustaining suppression system (described in main text as Y-drive). Hemizygous males then produce exclusively male offspring—all of which carry the Y-located transgene. D Aromatase SRD: All F₁ progeny will be phenotypically male, however 50% will carry female sex chromosomes (XX) “pseudomales”. In the F₂ generation, 75% of progeny produced by heterozygous XY males will develop as phenotypic males (XX heterozygotes converted to pseudomales) while XX pseudomales will produce progeny at a 50:50 phenotypic sex ratio

Fig. 2

Inheritance and molecular mechanisms of two self-sustaining (gene-drive) strategies. A engineered haploinsufficient underdominance: Shown is a generic single-locus system analogous in function to Reeves (2014). In this system all individuals in the target population are homozygous wildtype at the endogenous haploinsufficient locus (HI gene—solid orange). Three genotypes are possible at the transgene locus. (1) Wild-type carrying no copies of the transgene (viable). (2) Transgene heterozygotes with one copy of the RNAi-resistant ‘rescue’ Haploinsufficient Gene (HI gene—orange hatched). This genotype has only one functional copy of the HI gene—the single transgenic copy, the two endogenous copies being suppressed by RNAi—and therefore suffers reduced fitness (non-viable). (3) Transgene homozygotes where endogenous HI gene expression is also disrupted, but is rescued by the presence of two copies of the RNAi-resistant HI gene (viable). (4) Once released into a target population, individuals will therefore suffer from reduced fitness if they mate with another genotype (heterozygotes have low fitness). (5) This creates an unstable equilibrium with the more predominant allele being driven to fixation. In the absence of transgene fitness costs, the invasion threshold of this system is 0.5 (black dotted line). B CRISPR–Cas9 homing-drive: depicted individual is initially transgene heterozygous. Homologous genomic regions are represented in green. (1) Cas9 endonuclease is expressed from the transgene and directed to a target site complementary to the linked and co-expressed sgRNA sequence. This sgRNA target site occurs within a genomic region homologous to the transgene insertion site (e.g. a wild-type homologous chromosome). (2) Cas9 cleaves this target locus and due to the homology of the transgene’s flanking regions with the cut target site it is used as a template for homology-directed DNA repair (HDR). (3) During this process the transgene is copied (homes) into the cleaved target locus creating a transgene homozygous cell. (4) If this process occurs in the germline, offspring of individuals heterozygous for the sgRNA-Cas9 transgene will inherit the gene-drive at above normal rates (‘super-Mendelian inheritance’). For example, transmission rates above 90% have been observed in Drosophila and mosquitoes (Hammond et al. ; Gantz ; Gantz and Bier 2015), rather than the 50% expected from Mendelian inheritance