Locally Fixed Alleles: A method to localize gene drive to island populations

Jaye Sudweeks, Brandon Hollingsworth, Dimitri V. Blondel, Karl J. Campbell, Sumit Dhole, John D. Eisemann, Owain Edwards, John Godwin, Gregg R. Howald, Kevin P. Oh, Antoinette J. Piaggio, Thomas A.A. Prowse, Joshua V. Ross, J. Royden Saah, Aaron B. Shiels, Paul Thomas, David W. Threadgill, Michael R. Vella, Fred Gould, Alun L. Lloyd

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.

LanguageEnglish
Article number15821
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

ASJC Scopus subject areas

  • General

Cite this

Sudweeks, J., Hollingsworth, B., Blondel, D. V., Campbell, K. J., Dhole, S., Eisemann, J. D., ... Lloyd, A. L. (2019). Locally Fixed Alleles: A method to localize gene drive to island populations. Scientific Reports, 9(1), [15821]. https://doi.org/10.1038/s41598-019-51994-0
Sudweeks, Jaye ; Hollingsworth, Brandon ; Blondel, Dimitri V. ; Campbell, Karl J. ; Dhole, Sumit ; Eisemann, John D. ; Edwards, Owain ; Godwin, John ; Howald, Gregg R. ; Oh, Kevin P. ; Piaggio, Antoinette J. ; Prowse, Thomas A.A. ; Ross, Joshua V. ; Saah, J. Royden ; Shiels, Aaron B. ; Thomas, Paul ; Threadgill, David W. ; Vella, Michael R. ; Gould, Fred ; Lloyd, Alun L. / Locally Fixed Alleles : A method to localize gene drive to island populations. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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abstract = "Invasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.",
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Sudweeks, J, Hollingsworth, B, Blondel, DV, Campbell, KJ, Dhole, S, Eisemann, JD, Edwards, O, Godwin, J, Howald, GR, Oh, KP, Piaggio, AJ, Prowse, TAA, Ross, JV, Saah, JR, Shiels, AB, Thomas, P, Threadgill, DW, Vella, MR, Gould, F & Lloyd, AL 2019, 'Locally Fixed Alleles: A method to localize gene drive to island populations', Scientific Reports, vol. 9, no. 1, 15821. https://doi.org/10.1038/s41598-019-51994-0

Locally Fixed Alleles : A method to localize gene drive to island populations. / Sudweeks, Jaye; Hollingsworth, Brandon; Blondel, Dimitri V.; Campbell, Karl J.; Dhole, Sumit; Eisemann, John D.; Edwards, Owain; Godwin, John; Howald, Gregg R.; Oh, Kevin P.; Piaggio, Antoinette J.; Prowse, Thomas A.A.; Ross, Joshua V.; Saah, J. Royden; Shiels, Aaron B.; Thomas, Paul; Threadgill, David W.; Vella, Michael R.; Gould, Fred; Lloyd, Alun L.

In: Scientific Reports, Vol. 9, No. 1, 15821, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Hollingsworth, Brandon

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AU - Eisemann, John D.

AU - Edwards, Owain

AU - Godwin, John

AU - Howald, Gregg R.

AU - Oh, Kevin P.

AU - Piaggio, Antoinette J.

AU - Prowse, Thomas A.A.

AU - Ross, Joshua V.

AU - Saah, J. Royden

AU - Shiels, Aaron B.

AU - Thomas, Paul

AU - Threadgill, David W.

AU - Vella, Michael R.

AU - Gould, Fred

AU - Lloyd, Alun L.

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Sudweeks J, Hollingsworth B, Blondel DV, Campbell KJ, Dhole S, Eisemann JD et al. Locally Fixed Alleles: A method to localize gene drive to island populations. Scientific Reports. 2019 Dec 1;9(1). 15821. https://doi.org/10.1038/s41598-019-51994-0