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Quantifying Fitness Costs in Transgenic Aedes aegypti Mosquitoes

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Evading resistance to gene drives.

Richard Gomulkiewicz¹, Micki L Thies¹, James J Bull²

¹School of Biological Sciences, Washington State University, Pullman, WA 99164, USA.

|March 16, 2021

Summary

This summary is machine-generated.

Mathematical models show that carefully designed gene drives can evade resistance, even when resistance is initially present. Linkage between gene drive and resistance loci is key to preventing resistance evolution in wild populations.

Keywords:

CRISPR gene drive homing drive nonallelic resistance population suppression toxin-antidote drive

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Area of Science:

Genetics
Evolutionary Biology
Computational Biology

Background:

Gene drives, particularly CRISPR-based systems, offer powerful tools for altering wild populations.
Population suppression gene drives face a significant challenge from the evolution of resistance.
Existing models often assume resistance is allelic to the drive, limiting their scope.

Purpose of the Study:

To identify conditions under which population suppression gene drives can evade resistance evolution.
To explore the role of linkage between drive and resistance loci in resistance evolution.
To compare the resistance-evolution potential of different gene drive designs, such as homing versus toxin-antidote systems.

Main Methods:

Development of mathematical and computational models to simulate gene drive dynamics.
Analysis of gene drive and resistance locus interactions, including linkage and linkage disequilibrium.
Modeling of different resistance scenarios, including dominant and recessive resistance, and varying levels of inviability.

Main Results:

Linkage between resistance and drive loci is critical; negative linkage disequilibrium favors resistance evolution.
Unlinked or partially linked loci allow suppression drives with limited inviability to fix with minimal resistance increase.
Toxin-antidote systems appear less prone to selecting resistance than homing drives.
Dominant resistance that fully suppresses transmission distortion in homing drives is most susceptible to evolution.

Conclusions:

Gene drive design, particularly the linkage of resistance and drive loci, is crucial for preventing resistance.
CRISPR-based gene drives can be engineered to be effectively resistance-proof by carefully considering these genetic factors.
Multiple drives, potentially delivered sequentially, could achieve high levels of population suppression while minimizing resistance evolution.