BishtRef
Articles Journals Publishers Authors Subjects Most Cited New Papers Year Stats Open Access
journal article Open Access Mar 25, 2020

Population‐level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus

Matthew P. Edgington ORCID Tim Harvey‐Samuel Luke Alphey ORCID
Evolutionary Applications Vol. 13 No. 8 pp. 1939-1948 · Wiley
View at Publisher Save 10.1111/eva.12945
Abstract
AbstractCRISPR‐based gene drives bias inheritance in their favour by inducing double‐stranded breaks (DSBs) at wild‐type homologous loci and using the drive transgene as a repair template—converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end‐joining repair mechanisms produce cut‐resistant alleles that rapidly induce drive failure. Multiplexing—simultaneously targeting multiple sites at the wild‐type locus—is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut‐resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population‐level multiplexing approaches with standard individual‐level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement, while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility, we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.
Topics

No keywords indexed for this article. Browse by subject →

References
37
Metrics
19
Citations
37
References
Details
Published
Mar 25, 2020
Vol/Issue
13(8)
Pages
1939-1948
License
View
Authors
M
Matthew P. Edgington

The Pirbright Institute Woking UK

T
Tim Harvey‐Samuel

The Pirbright Institute Woking UK

L
Luke Alphey

The Pirbright Institute Woking UK

Cite This Article
Matthew P. Edgington, Tim Harvey‐Samuel, Luke Alphey (2020). Population‐level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus. Evolutionary Applications, 13(8), 1939-1948. https://doi.org/10.1111/eva.12945
Related

You May Also Like

Climate change, adaptation, and phenotypic plasticity: the problem and the evidence

Juha Merilä, Andrew P. Hendry · 2014

1,083 citations

Evolution and behavioural responses to human‐induced rapid environmental change

Andrew Sih, Maud C. O. Ferrari · 2011

1,040 citations

Linkage disequilibrium estimates of contemporary Ne using highly variable genetic markers: a largely untapped resource for applied conservation and evolution

Robin S. Waples, Chi Do · 2010

863 citations

Hybridization and extinction

Marco Todesco, Mariana A. Pascual · 2016

713 citations

Building evolutionary resilience for conserving biodiversity under climate change

Carla M. Sgrò, Andrew J. Lowe · 2010

662 citations