Gene drives for vertebrate pest control: Realistic spatial modelling of eradication probabilities and times for island mouse populations

Molecular Ecology, Journal Year: 2022, Volume and Issue: 31(6), P. 1907 - 1923

Published: Jan. 24, 2022

Invasive alien species continue to threaten global biodiversity. CRISPR-based gene drives, which can theoretically spread through populations despite imparting a fitness cost, could be used suppress or eradicate pest populations. We develop an individual-based, spatially explicit, stochastic model simulate the ability of homing and X chromosome shredding drives invasive house mice (Mus muculus) from islands. Using model, we explore interactive effect efficiency drive constructs spatial ecology target population on outcome gene-drive release. also consider impact polyandrous mating sperm competition, compromise efficacy some strategies. Our results show that both strategies large mice. Whereas parameters related demography strongly influence performance, find competition following is unlikely eradication effort substantially. Assumptions regarding influenced probability time required for eradication, with short-range dispersal capacities limited mate-search areas producing 'chase' dynamics across island characterized by cycles local extinction recolonization highly efficient are not always optimal, when capabilities low. Rapid suppression around introduction sites cause loss before it entire island. conclude that, although design undoubtedly critical, accurate data critical predicting result

Language: Английский

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Cleave and Rescue gamete killers create conditions for gene drive in plants

Nature Plants, Journal Year: 2024, Volume and Issue: 10(6), P. 936 - 953

Published: June 17, 2024

Language: Английский

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Slow and steady wins the race: Spatial and stochastic processes and the failure of suppression gene drives

Molecular Ecology, Journal Year: 2022, Volume and Issue: 31(17), P. 4451 - 4464

Published: July 5, 2022

Gene drives that skew sex ratios offer a new management tool to suppress or eradicate pest populations. Early models and empirical work suggest these suppression can completely well-mixed populations, but incorporate stochasticity space (i.e. drift recolonization events) often result in loss failure of the drive. We developed stochastic model examine processes simple one-dimensional space. This allows us map events outcomes emerged how properties drive's wave invasion affect outcomes. Our simulations, across biologically realistic section parameter space, drive might be common outcome spatially explicit, systems, appear mediate Surprisingly, would considered fittest an aspatial were strongly associated with spatial setting. The cause relatively fast moving, narrow waves have high chance being penetrated by wild-types (WTs) leading WT recolonization, failure. results also show rates dispersal reduce because get disproportionately wider than as increase. Overall, wide, slow-moving much less prone point complexity inherent using genetic system effect demographic speak clear need for ecological evolutionary modelling inform design process.

Language: Английский

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Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Oct. 14, 2022

Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such may be highly effective tools to combat malaria. One such drive, based on the zpg promoter driving CRISPR/Cas9, was able eliminate a cage of mosquitoes. A second version, purportedly improved upon first by incorporating an X-shredder element (which biases inheritance towards male offspring), similarly successful. Here, we analyze experimental data from each these extract their characteristics and performance parameters compare previous interpretations performance. We assess suppression drive within individual-based simulation framework models mosquito dynamics in continuous space. find combined homing/X-shredder is actually less at context our model. In particular, often fails completely suppress population, instead resulting unstable equilibrium between wild-type alleles. By contrast, otherwise similar nos prove more promising candidates for future development than originally thought.

Language: Английский

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Leveraging a natural murine meiotic drive to suppress invasive populations

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(46)

Published: Nov. 8, 2022

Invasive rodents are a major cause of environmental damage and biodiversity loss, particularly on islands. Unlike insects, genetic biocontrol strategies including population-suppressing gene drives with biased inheritance have not been developed in mice. Here, we demonstrate drive strategy (tCRISPR) that leverages super-Mendelian transmission the t haplotype to spread inactivating mutations haplosufficient female fertility (Prl). Using spatially explicit individual-based silico modeling, show tCRISPR can eradicate island populations under range realistic field-based parameter values. We also engineer transgenic mice that, crucially, exhibit modified Prl at levels our modeling predicts would be sufficient for eradication. This is an example feasible system invasive alien rodent population control.

Language: Английский

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Adversarial interspecies relationships facilitate population suppression by gene drive in spatially explicit models

Ecology Letters, Journal Year: 2023, Volume and Issue: 26(7), P. 1174 - 1185

Published: May 10, 2023

Suppression gene drives bias their inheritance to spread through a population, potentially eliminating it when they reach high frequency. CRISPR homing suppression have already seen success in the laboratory, but several models predict that may be elusive population with realistic spatial structure due extinction-recolonization cycles. Here, we extend our continuous space framework include two competing species or predator-prey pairs. We find both general and mosquito-specific models, predators can facilitate drive-based suppression, albeit at cost of an increased rate drive loss outcomes. These results are robust mosquito seasonal fluctuations. Our study illustrates difficulty predicting outcomes complex ecosystems. However, promising for prospects less powerful successfully eliminate target other pest populations.

Language: Английский

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Ecology of Gene Drives: The Role of Density‐Dependent Feedbacks on the Efficacy and Dynamics of Two‐Locus Underdominance Gene Drive Systems

Evolutionary Applications, Journal Year: 2025, Volume and Issue: 18(3)

Published: March 1, 2025

Density dependence describes the regulation of population growth rate by density. This process is widely observed in insect populations, including vectors such as mosquitoes and agricultural pests that are targets genetic biocontrol using gene drive technologies. While there continues to be rapid advancement molecular design, most studies prioritise efficacy over ecology, role density-dependent feedback on drives remains neglected. Furthermore, details density experienced these potential species interest usually poorly understood, creating additional constraints challenges evaluating efficiency systems, especially those promise local confinement after release. Here, we formulate analyse a simple, non-species-specific mathematical model which integrates dynamics together with genetics high-threshold two-locus underdominance system. Different models strengths within-species competition investigated alongside other ecological parameters. Our results suggest for an system, processes, acting births or deaths, influence leading significantly different population-level suppression presence fitness cost. However, does not directly affect cost threshold establishment. Moreover, find magnitude range key parameters (birth death rates) could result outcomes depending type employed. work highlights importance considering contexts development deployment strategies.

Language: Английский

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Maximising Eradication Potential of Rat Gene Drives Using a Two‐Target Homing Rescue Strategy: Spatial Modelling of Empirical Data

Molecular Ecology, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

ABSTRACT Gene drives are genetic elements with positively biased transmission and may be useful tools to suppress mammalian pests that threaten biodiversity worldwide. While gene progressing in mice, less is known about their potential for invasive rat control. A recent report has provided the first data on germline conversion rats, demonstrating modest homing rates (up 67%) can achieved females. Here, we apply these empirically derived values investigate of various drive strategies an island population 200,000 using our stochastic, spatially explicit, individual‐based modelling framework. Standard embedded haplosufficient fertility or viability genes failed eradicate, but permanent suppression. In contrast, a two‐target design rescue (HR) haplolethal also targets independent demonstrated considerable suppression potential. Remarkably, HR targeting female showed robust eradication even at relatively low previously rats. Interestingly, rate had influence probability while cutting efficiency was critical. Further, as long latter similar subsequent knockout unlinked gene, then could across range rates. Together, results suggest rates, such have been rats other species, potentially leveraged suppression, offering new opportunities development.

Language: Английский

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Performance characteristics allow for confinement of a CRISPR toxin–antidote gene drive for population suppression in a reaction–diffusion model

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 291(2025)

Published: June 1, 2024

Gene drive alleles that can bias their own inheritance could engineer populations for control of disease vectors, invasive species and agricultural pests. There are successful examples suppression drives confined modification drives, but developing has proven more difficult. However, CRISPR-based toxin–antidote dominant embryo (TADE) may fill this niche. It works by targeting disrupting a haplolethal target gene in the germline with its gRNAs while rescuing target. also disrupts female fertility driving insertion or additional gRNAs. Here, we used reaction–diffusion model to assess performance continuous space, where outcomes be substantially different from those panmictic populations. We measured wave speed found moderate fitness costs disruption early maternally deposited nuclease eliminate drive’s ability form advance. assessed required release size, finally investigated migration corridor scenarios. is often possible suppress one population then persist without invading second population, potentially desirable outcome. Thus, even imperfect variants TADE excellent candidates suppression.

Language: Английский

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Scalability of genetic biocontrols for eradicating invasive alien mammals

NeoBiota, Journal Year: 2022, Volume and Issue: 74, P. 93 - 103

Published: July 7, 2022

CRISPR-based gene drives offer novel solutions for controlling invasive alien species, which could ultimately extend eradication efforts to continental scales. Gene suppressing vertebrates are now under development. Using a landscape-scale individual-based model, we present the first estimates of times long-lived mammals. We show that demography and life-history traits interact determine scalability vertebrate pest eradication. Notably, optimism around eradicating smaller-bodied pests (rodents rabbits) with gene-drive technologies does not easily translate into larger-bodied species (cats foxes).

Language: Английский

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