Can CRISPR gene drive work in pest and beneficial haplodiploid species?

Jun Li,Linda L Walling,Bruce E Tabashnik,Ofer Aidlin Harari,Peter W Atkinson,Shai Morin,Anna-Louise Doss

doi:10.1111/eva.13032

Abstract

Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known about CRISPR gene drive in haplodiploids, despite their immense global impacts as pollinators, pests, natural enemies of pests, and invasive species in native habitats. Here, we analyze mathematical models demonstrating that, in principle, CRISPR homing gene drive can work in haplodiploids, as well as at sex‐linked loci in diploids. However, relative to diploids, conditions favoring the spread of alleles deleterious to haplodiploid pests by CRISPR gene drive are narrower, the spread is slower, and resistance to the drive evolves faster. By contrast, the spread of alleles that impose little fitness cost or boost fitness was not greatly hindered in haplodiploids relative to diploids. Therefore, altering traits to minimize damage caused by harmful haplodiploids, such as interfering with transmission of plant pathogens, may be more likely to succeed than control efforts based on introducing traits that reduce pest fitness. Enhancing fitness of beneficial haplodiploids with CRISPR gene drive is also promising.

Highlights

Because Cas9 can target almost any sequence that is followed by a protospacer adjacent motif (PAM), RNA-guided gene drive elements can be constructed by inserting a suitable sequence encoding Cas9 and one or more guide RNA (gRNA)
We modeled the evolutionary dynamics of the CRISPR gene drive with the potential for evolution of resistance to drive under two scenarios
In contrast with the extensive empirical and theoretical studies of CRISPR gene drive in diploid organisms, relatively little is known about this issue in haplodiploids despite their immense global impacts

Summary

| INTRODUCTION

Gene drive mediated by the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system has recently emerged as one of the most promising technologies for reducing the harm caused by insect vectors of disease, crop pests, and invasive species, as well as for enhancing the fitness of valued species (Champer et al, 2018; Eckhoff, Wenger, Godfray, & Burt, 2017; Esvelt, Smidler, Catteruccia, & Church, 2014; Gantz et al, 2015; Godfray, North, & Burt, 2017; Grunwald et al, 2019; Kyrou et al, 2018; Rode, Estoup, Bourguet, Courtier-Orgogozo, & Débarre, 2019; Scott et al, 2018). In parallel with empirical work, mathematical modeling and computer simulations have been essential for evaluating the feasibility, limitations, risks, and benefits associated with CRISPR gene drives (Champer et al, 2020; Deredec, Burt, & Godfray, 2008; Deredec, Godfray, & Burt, 2011; Eckhoff et al, 2017; Godfray et al, 2017; Hammond et al, 2016; Noble et al, 2017; Rode et al, 2019; Unckless, Clark, & Messer, 2017; Unckless, Messer, Connallon, & Clark, 2015) This theoretical work has identified evolution of resistance to the drive as a major limitation and greatly advanced understanding of the expected evolutionary trajectories of CRISPR gene drives in diploid species, mosquito vectors of human disease. The spread of alleles that cause little fitness cost or enhance fitness was not greatly hindered in haplodiploids relative to diploids

| METHODS

Findings

| DISCUSSION