Evolutionary simulations ofZ-linked suppression gene drives

Abstract

Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z -linked gene drives to control species with ZW sex determination, which include Lepidopteran pests, parasitic trematodes, and cane toads. These proposals include Z -linked ‘ W -shredders’, which would suppress populations by cleaving the W chromosome and causing females to produce only sons, as well as Z -linked female-sterilizing gene drives. Here, I use eco-evolutionary simulations to evaluate the potential of some proposed Z -linked gene drives, and to produce recommendations regarding their design and use. The simulations show that W -shredders are likely to be highly effective at eradicating populations provided that resistance to W -shredding cannot evolve. However, W -shredder alleles can invade populations from very low frequencies, making it difficult to eliminate specific populations while leaving nearby populations untouched; this issue may restrict their possible uses.

A common gene drive language eases regulatory process and eco-evolutionary extensions

“…Suppression drives -intended to eradicate or reduce the target population or 'reversal drives' -intended to reverse the genetic alteration introduced by the first gene drive [Esvelt et al, 2014, DiCarlo et al, 2015, Vella et al, 2017, Edgington and Alphey, 2019 are not included in the app. Some newly proposed gene drive systems that are mainly intended for suppression but can also be used for replacement, such as CleavR, TARE, TADE, double-drives and Y-linked editors, cannot be currently modelled in this study [Oberhofer et al, 2020, 2019, Champer et al, 2020a,b, Willis and Burt, 2021, Prowse et al, 2019. Classification of such complex drive system based on our mathematical model would also be problematic since these might have very complex selection mechanisms or have simple mechanisms but whose dynamics critically depend on the genetic makeup of different populations.…”

“…Other such properties of interest are the speed of action, reversibility, and potential to be spatially confined to only target populations. The sensitivity of such fundamental properties of drive systems to drive parameters has been a topic of interest of numerous recent theoretical studies [Huang et al, 2011, Akbari et al, 2013, Vella et al, 2017, Eckhoff et al, 2017, Noble et al, 2018, Edgington and Alphey, 2018, Dhole et al, 2018, Edgington and Alphey, 2019, Holman, 2019, Champer et al, 2020c. We have collated this material in the provided database.…”

Resistance to natural and synthetic gene drive systems

“…The lack of target‐site resistance, at least when observed at the limited scale of population cage experiments, reflects the use of extremely conserved rDNA target sequences which are present in hundreds of copies on the X chromosome, although even this cannot completely remove the possibility of resistance evolving. Gene drive systems targeting the heterogametic sex chromosome have only been investigated theoretically (Holman, 2019; Prowse et al., 2019) and in preliminary experiments in a house mouse system (Prowse et al., 2019).…”

“…As a result, many natural drivers have been completely suppressed, only showing drive when crossed into distant relatives that do not carry suppressor alleles (Courret, Chang, Wei, Montchamp‐Moreau, & Larracuente, 2019; McDermott & Noor, 2010). This research suggests that we should expect synthetic gene drives, especially those with large fitness effects, to select for resistance, which will potentially undermine their ability to spread, and modify or suppress populations (Barrett et al., 2019; Holman, 2019; Unckless et al., 2017).…”

Modeling CRISPR gene drives for suppression of invasive rodents

“…One possibility is that the drive is simply lost, either due to fitness effects or competition, or even due to local collapse before the drive is able to sufficiently spread (we did not observe such a scenario when parameters were set to their defaults, but it can occur in other areas of the parameter space). Another possibility is that the drive is not lost, but does not have sufficient suppressive power to fully eliminate the population (which can be caused by low drive performance or permissive ecological conditions), resulting in the population size declining to a new equilibrium size 12,36,43,85 . This was observed in the homing drive with a haplosufficient viability target at intermediate efficiency.…”