Keywords: gene drive models

A 2-locus model for polymorphism for sex-linked meiotic drive modifiers with possible applications to Aedes aegypti

Maffi, GJ, S. D.,  Theoretical Population Biology,  19:19-36. 1981.
A two-locus model is presented which shows the possibility of maintaining a polymorphism for modifiers of sex-linked meiotic drive in the absence of fitness differences. The model is very similar to the situation actually found in some laboratory strains of the mosquito Aedes ...
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A comparative approach to the population genetics theory of segregation distortion

Feldman, MWO, Sarah P.,  American Naturalist,  137:443-456. 1991.
Mathematical models of four well-known naturally occurring systems of segregation distortion are compared. These include the sex-ratio chromosome of Drosophila pseudoobscura, the Segregation Distorter (SD) complex of D. melanogaster, the t locus in Mus musculus, and the sex-ratio ...
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A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs

Gould, FH, Yunxin; Legros, Mathieu; Lloyd, Alun L.,  Proceedings of the Royal Society B: Biological Sciences,  275:2823-2829. 2008.
A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. ...
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A novel meiotic drive locus almost completely distorts segregation in Mimulus (monkeyflower) hybrids

Fishman, LW, J. H.,  Genetics,  169:347-353. 2005.
We report the discovery, mapping, and characterization of a meiotic drive locus (D) exhibiting nearly 100% nonrandom transmission in hybrids between two species of yellow monkeyflowers, outcrossing Mimulus guttatus and selfing M. nasutus. Only 1% of F-2 hybrids were M. nasutus ...
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A theoretical-analysis of the effects of sex-chromosome aneuploidy on X-chromosome and Y-chromosome meiotic drive

Lyttle, TW,  Evolution,  36:822-831. 1982.
Extra sex chromosomes are normally detrimental to the individual carrying them. In XY (or WZ) sex determining systems, an extra X chromosome in the homogametic sex generates enough X-autosome imbalance to usually cause inviability, or at least sterility. On the oth- er hand, ...
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A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

V. López Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  Nature Communications,  11:352. 2020.
CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and ...
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A unifying approach to gene drive

P. Verma, R. Reeves and C. S. Gokhale,  bioRxiv,  2020.02.28.970103. 2020.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The properties of gene drive constructs are diverse and depend on their molecular construction, and differential selection pressure ...
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A Y-chromosome shredding gene drive for controlling pest vertebrate populations

Prowse, TAAA, F.; Cassey, P.; Thomas, P.; Ross, J. V.,  eLife,  8:19. 2019.
Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within ...
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An unusual sex-determination system in South American field mice (genus Akodon): The role of mutation, selection, and meiotic drive in maintaining XY females

Hoekstra, HEH, J. M.,  Evolution,  55:190-197. 2001.
The mechanism of sex determination in mammals appears highly conserved: the presence of a Y chromosome triggers the male developmental pathway, whereas the absence of a Y chromosome results in a default female phenotype. However, if the Y chromosome fails to initiate the male ...
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Analysis of a general population genetic model of meiotic drive

Hartl, DL,  Evolution,  24:538-545. 1970.
The purpose of this article is to present the detailed solution of a model of meiotic drive which Lewontin (1968) has suggested would be helpful in understanding the evo- lutionary dynamics of the t-alleles in the house mouse. Because mice tend to breed in small endogamous family ...
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Analysis of meiotic segregation, using single-sperm typing: Meiotic drive at the myotonic dystrophy locus

Leeflang, EPM, M. S.; Arnheim, N.,  American Journal of Human Genetics,  59:896-904. 1996.
Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of ...
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B-chromosome drive

Jones, RN,  American Naturalist,  137:430-442. 1991.
The view of B-chromosome polymorphisms that is coming into favor resembles the so-called "parasitic" model, which was first advanced 45 yr ago. Since that time, repeated and ongoing efforts have been made to ascribe an adaptive role to B's (e.g., in terms of phenotypic advantage, ...
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Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement

Cha, SJM, A.; Chadee, D. D.; Severson, D. W.,  American Journal of Tropical Medicine and Hygiene,  74:62-68. 2006.
Control of arthropod-borne diseases based on population replacement with genetically modified noncompetent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry ...
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  bioRxiv,  2020.03.17.995829. 2020.
CRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations through the release of individuals carrying an engineered piece of DNA that can be inherited by all their progeny. Developing countermeasures is important to control ...
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Can a population targeted by a CRISPR-based homing gene drive be rescued?

N. O. Rode, V. Courtier-Orgogozo and F. Débarre,  G3-Genes Genomes Genetics,  2020.
N. O. Rode, V. Courtier-Orgogozo and F. Débarre (2020). G3 doi: 10.1534/g3.120.401484 Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals ...
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Can CRISPR gene drive work in pest and beneficial haplodiploid species?

J. Li, O. Aidlin Harari, A.-L. Doss, L. L. Walling, P. W. Atkinson, S. Morin and B. E. Tabashnik,  Evolutionary Applications,  2020.
Gene drives based on CRISPR/Cas9 have the potential to reduce the enormous harm inflicted by crop pests and insect vectors of human disease, as well as to bolster valued species. In contrast with extensive empirical and theoretical studies in diploid organisms, little is known ...
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Can CRISPR-based gene drive be confined in the Wild? A question for molecular and population biology

Marshall, JMA, Omar S.,  ACS Chemical Biology,  13:424-430. 2018.
The recent discovery of CRISPR and its application as a gene editing tool has enabled a range of gene drive systems to be engineered with greater ease. In order for the benefits of this technology to be realized, in some circumstances drive systems should be developed that are ...
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Case Study 1: Olive Fruit Fly (Bactrocera oleae)

Merle Preu, Johannes L. Frieß, Broder Breckling and Winfried Schröder,  Gene Drives at Tipping Points,  2020.
The olive fruit fly Bactrocera oleae is a phytophagous insect associated to olive trees (Olea europaea, Oleaceae). Its larvae monophagously feed on olive fruits, the fly is therefore considered the most severe pest of olive cultivation causing tremendous economic losses. The ...
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Catch me if you can: A spatial model for a brake-driven gene drive reversal

Calvez, V,,Debarre, F., Girardin, Leo,  arXiv,  1812.06641:1-30. 2018.
We successfully prove that, whenever the drive fitness is at most 50% of the wild-type one while the brake fitness is close to the wild-type one, co-extinction of the brake and the drive occurs in the long run.
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Centromere-associated female meiotic drive entails male fitness costs in Monkeyflowers

Fishman, LS, A.,  Science,  322:1559-1562. 2008.
Female meiotic drive, in which paired chromosomes compete for access to the egg, is a potentially powerful but rarely documented evolutionary force. In interspecific monkeyflower ( Mimulus) hybrids, a driving M. guttatus allele ( D) exhibits a 98: 2 transmission advantage via ...
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Centromere-associated meiotic drive and female fitness variation in Mimulus

Fishman, LK, J. K.,  Evolution,  69:1208-1218. 2015.
Female meiotic drive, in which chromosomal variants preferentially segregate to the egg pole during asymmetric female meiosis, is a theoretically pervasive but still mysterious form of selfish evolution. Like other selfish genetic elements, driving chromosomes may be maintained ...
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Coevolutionary dynamics of polyandry and sex-linked meiotic drive

Holman, LP, T. A. R.; Wedell, N.; Kokko, H.,  Evolution,  69:709-720. 2015.
Segregation distorters located on sex chromosomes are predicted to sweep to fixation and cause extinction via a shortage of one sex, but in nature they are often found at low, stable frequencies. One potential resolution to this longstanding puzzle involves female multiple mating ...
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Competition between segregation distorters: Coexistence of ”superior” and ”inferior” haplotypes at the t complex

vanBoven, MW, F. J.; Heg, D.; Huisman, J.,  Evolution,  50:2488-2498. 1996.
By means of population genetical models, we investigate the competition between sex-specific segregation distorters. Although the models are quite general, they are motivated by a specific example, the t complex of the house mouse. Some variants at this gene complex, the t ...
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Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs

S. E. Champer, S. Y. Oh, C. Liu, Z. Wen, A. G. Clark, P. W. Messer and J. Champer,  Science Advances,  6:eaaz0525. 2020.
The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, ...
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Conditions for success of engineered underdominance gene drive systems

Edgington, MPA, L. S.,  Journal of Theoretical Biology,  430:128-140. 2017.
Engineered underdominance is one of a number of different gene drive strategies that have been proposed for the genetic control of insect vectors of disease. Here we model a two-locus engineered underdominance based gene drive system that is based on the concept of mutually ...
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Confinement of gene drive systems to local populations: A comparative analysis

Marshall, JMH, B. A.,  Journal of Theoretical Biology,  294:153-171. 2012.
Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered ...
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Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management

KaramiNejadRanjbar, ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A.,  Proceedings of the National Academy of Sciences of the United States of America,  115:6189-6194. 2018.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles ...
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Controlling invasive rodents via synthetic gene drive and the role of polyandry

Manser, AC, S. J.; Sutter, A.; Blondel, D. V.; Serr, M.; Godwin, J.; Price, T. A. R.,  Proceedings of the Royal Society B-Biological Sciences,  286:9. 2019.
House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive ...
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Correction to ‘Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates’

Prowse, TAAC, Phillip; Ross, Joshua V.; Pfitzner, Chandran; Wittmann, Talia; Thomas, Paul,  Proceedings of the Royal Society B: Biological Sciences,  285:1-2. 2018.
Proc. R. Soc. B 284, 20170799. (Published Online 9 August 2017). (doi:10.1098/rspb.2017.0799)We recently found an error in our calculation of the probability of a wild-type allele moving from s to j susceptible sites (), and acquiring the gene drive (), during gene-drive homing, ...
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Current CRISPR gene drive systems are likely to be highly invasive in wild populations

Noble, CA, Ben; Church, George M.; Esvelt, Kevin M.; Nowak, Martin A.,  eLife,  7:e33423. 2018.
Recent reports have suggested that self-propagating CRISPR-based gene drive systems are unlikely to efficiently invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test ...
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Daisy-chain gene drives for the alteration of local populations

Noble, CM, J.; Olejarz, J.; Buchthal, J.; Chavez, A.; Smidler, A. L.; DeBenedictis, E. A.; Church, G. M.; Nowak, M. A.; Esvelt, K. M.,  Proceedings of the National Academy of Sciences of the United States of America,  116:8275-8282. 2019.
If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, ...
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drives

Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer,  bioRxiv,  861435:861435. 2019.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based ...
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Divergence of meiotic drive-suppression systems as an explanation for sex-biased hybrid sterility and inviability

Frank, SA,  Evolution,  45:262-267. 1991.
Two empirical generalizations about speciation remain unexplained: the tendency of the heterogametic sex to be sterile or inviable in F1 hybrids (Haldane's rule), and the tendency of the X chromosome to harbor the genetic elements that cause this sex bias in hybrid fitness. I ...
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Dodging silver bullets: good CRISPR gene-drive design is critical for eradicating exotic vertebrates

Prowse, TAAC, Phillip; Ross, Joshua V.; Pfitzner, Chandran; Wittmann, Talia A.; Thomas, Paul,  Proceedings of the Royal Society B: Biological Sciences,  284:20170799. 2017.
Self-replicating gene drives that can spread deleterious alleles through animal populations have been promoted as a much needed but controversial ‘silver bullet’ for controlling invasive alien species. Homing-based drives comprise an endonuclease and a guide RNA (gRNA) that ...
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Dynamics of a combined medea-underdominant population transformation system

Gokhale, CSR, R. G.; Reed, F. A.,  BMC Evolutionary Biology,  14:98. 2014.
: Transgenic constructs intended to be stably established at high frequencies in wild populations have been demonstrated to "drive" from low frequencies in experimental insect populations. Linking such population transformation constructs to genes which render them unable to ...
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Embracing Dynamic Models for Gene Drive Management

A. J. Golnar, E. Ruell, A. L. Lloyd and K. M. Pepin,  Trends in Biotechnology,  2020.
We describe how quantitative tools can reduce risk uncertainty, streamline empirical research, guide risk management, and promote cross-sector collaboration throughout the process of gene drive technology development and implementation.
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Engineering synthetic medea-based and threshold- dependent underdominance-based gene drive systems in mosquitoes

Akbari, OM, J.; Antoshechkin, I.; Matzen, K.; Papathanos, P.; Kennedy, K.; Ward, C.; Chen, C. H.; Guo, M.; Hay, B.,  Pathogens and Global Health,  107:442-442. 2013.
Mosquito population replacement requires gene drive mechanisms in order to spread linked genes, mediating disease refractoriness, through wild populations. Medea is predicted to be a low threshold gene drive mechanism, able to spread from low initial frequency. Such a system is ...
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Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.
Here we develop mathematical and computational models to identify conditions under which suppression drives will evade resistance, even if resistance is present initially.
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Evading evolution of resistance to gene drives

R. Gomulkiewicz, M. L. Thies and J. J. Bull,  bioRxiv,  2020.08.27.270611. 2020.