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{"title"=>"Medusa: A novel gene drive system for confined suppression of insect populations", "type"=>"journal", "authors"=>[{"first_name"=>"John M.", "last_name"=>"Marshall", "scopus_author_id"=>"55471919700"}, {"first_name"=>"Bruce A.", "last_name"=>"Hay", "scopus_author_id"=>"7006167912"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25054803", "sgr"=>"84904622855", "doi"=>"10.1371/journal.pone.0102694", "scopus"=>"2-s2.0-84904622855", "pui"=>"373596272", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"d10b74d2-0a14-3361-87fc-8d0640c43353", "abstract"=>"Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, Medusa, capable of inducing a local and reversible population crash. Medusa consists of four components--two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of Medusa-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of Medusa males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of Medusa males. Finally, we outline how Medusa could be engineered with currently available molecular tools.", "link"=>"http://www.mendeley.com/research/medusa-novel-gene-drive-system-confined-suppression-insect-populations", "reader_count"=>38, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>12, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>4, "Student > Bachelor"=>3, "Lecturer > Senior Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Mathematics"=>1, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>23, "Veterinary Science and Veterinary Medicine"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Decision Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>23}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1, "United Kingdom"=>3, "Mexico"=>1, "Switzerland"=>1}, "group_count"=>7}

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• http://doi.org/10.1111/eva.12583
• http://doi.org/10.1038/nrg.2015.34
• http://doi.org/10.1371/journal.pcbi.1006059
• http://doi.org/10.1073/pnas.1805278115
• http://doi.org/10.1038/nbt.3361

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1606397"], "description"=>"<p>A: Gene drive and elimination of females following two consecutive releases of males carrying the <i>Medusa</i> system (no fitness cost) at a population frequency of 50% (i.e. released males represent 50% of the population post-release for each of the two releases). B: Threshold properties of the <i>Medusa</i> system (no fitness cost) – two consecutive releases of males at a population frequency of 42% results in gene drive; while two releases at a population frequency of 41% result in transgene elimination. C: Population suppression following six consecutive releases of 10,000 males carrying the <i>Medusa</i> system (no fitness cost) into a population with a carrying capacity of 10,000 and a growth rate of 9.1. Results depicted are a single run of the stochastic simulation. As the population becomes increasingly transgenic, the number of females declines, resulting in a population crash within ∼12 generations. D: <i>Medusa</i> release thresholds as a function of fitness cost under the: a) deterministic model, b) stochastic model where a fitness cost corresponds to an increase in mosquito mortality rate, and c) where it corresponds to a decrease in female mosquito fertility rate. For the deterministic model, release thresholds correspond to two consecutive releases of transgenic males representing a given population frequency; whereas, for the stochastic model, release thresholds are measured by the number of releases of 10,000 transgenic males (i.e. a population frequency of ∼50%) required to induce a population crash. For the stochastic model, the threshold number of releases was taken as the mode of 11 simulations.</p>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases"], "article_id"=>1115533, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102694.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Medusa_dynamics_in_a_single_population_/1115533", "title"=>"<i>Medusa</i> dynamics in a single population.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:40:54"}
• {"files"=>["https://ndownloader.figshare.com/files/1606396"], "description"=>"<p><i>Medusa</i> consists of four components – two at a locus on the X chromosome and two at a locus on the Y chromosome. The action of the maternally-expressed, X-linked toxin is suppressed in zygotes that inherit the Y-linked antidote. The effects of the zygotically-expressed, Y-linked toxin are suppressed in zygotes inheriting the X-linked antidote.</p>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases", "inheritance"], "article_id"=>1115532, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102694.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Components_and_inheritance_pattern_of_the_Medusa_system_/1115532", "title"=>"Components and inheritance pattern of the <i>Medusa</i> system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:40:54"}
• {"files"=>["https://ndownloader.figshare.com/files/1606401", "https://ndownloader.figshare.com/files/1606402"], "description"=>"<div><p>Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, <i>Medusa</i>, capable of inducing a local and reversible population crash. <i>Medusa</i> consists of four components - two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of <i>Medusa</i>-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of <i>Medusa</i> males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of <i>Medusa</i> males. Finally, we outline how <i>Medusa</i> could be engineered with currently available molecular tools.</p></div>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases", "confined", "suppression", "populations"], "article_id"=>1115537, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0102694.s001", "https://dx.doi.org/10.1371/journal.pone.0102694.s002"], "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Medusa_A_Novel_Gene_Drive_System_for_Confined_Suppression_of_Insect_Populations/1115537", "title"=>"<i>Medusa</i>: A Novel Gene Drive System for Confined Suppression of Insect Populations", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-23 03:40:54"}
• {"files"=>["https://ndownloader.figshare.com/files/1606399"], "description"=>"<p>A: Initial population suppression following 30 consecutive releases of males homozygous for the female-specific RIDL allele (no fitness cost) into an isolated population. Results depicted are a single run of the stochastic simulation. B: Sustained population suppression achieved through regular releases of 5,000 males homozygous for the female-specific RIDL allele into population C at each half generation following 20 initial releases of 10,000 transgenic males (bi-directional migration rate of 1% per generation). C: Initial population suppression following 30 consecutive releases of males homozygous for the autosomal X-shredder allele (no fitness cost, transgenic males have 90% male offspring) into an isolated population. D: Sustained population suppression achieved through regular releases of 2,500 males homozygous for the autosomal X-shredder allele into population C at each generation following 20 initial releases of 10,000 transgenic males (bi-directional migration rate of 1% per generation).</p>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases", "female-specific", "ridl", "autosomal"], "article_id"=>1115535, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102694.g004", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Population_dynamics_of_female_specific_RIDL_and_autosomal_X_shredders_/1115535", "title"=>"Population dynamics of female-specific RIDL and autosomal X-shredders.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:40:54"}
• {"files"=>["https://ndownloader.figshare.com/files/1606400"], "description"=>"<p>A: To generate flies carrying the <i>Medusa</i> X chromosome (top), a construct carrying two cassettes (regions enclosed by brackets), each consisting of multiple genes, is introduced onto the X chromosome. Cassette 1 consists of maternal toxin 1 (Maternal T1) and zygotic antidote 2 (Zygotic A2). Cassette 2 carries zygotic antidote 1 (Zygotic A1). It also carries a set of flanking genes that can be used to excise Zygotic A1 from the chromosome in response to the presence of tetracycline. This is achieved as follows: a germline-restricted promoter drives the expression of the rtTA gene, which encodes a tetracycline-dependent transcriptional activator <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102694#pone.0102694-Lycett1\" target=\"_blank\">[60]</a>. In the absence of tetracycline (upper chromosome), rtTA does not bind its target sites. Both sexes survive, as do all progeny of females carrying this construct. In the presence of tetracycline (middle chromosome), rtTA binds its target sites and drives the transcription of the FLP recombinase. FLP binds to two target sites (FRTs) and promotes the recombinational excision of the intervening genetic elements, which include a transcriptional stop sequence that prevents a ubiquitous promoter from driving expression of rtTA in all cells, and the rtTA, FLP and Zygotic A1 genes. Excision results in the creation of a chromosome (bottom chromosome) that carries cassette 1 and a newly created cassette 3, which consists of a ubiquitous promoter driving the expression of RFP, a visible marker. Female flies carrying this construct alone are sterile because no progeny inherit zygotic antidote 1, which is needed in order for progeny of mothers carrying maternal toxin 1 to survive. To generate flies carrying the <i>Medusa</i> Y chromosome (lower three chromosomes in A), a construct that carries two cassettes, each consisting of multiple genes, is introduced onto the Y chromosome. Cassette 1 consists of zygotic toxin 2 (Zygotic T2) and zygotic antidote 1 (Zygotic A1). Insects carrying this chromosome survive because they also carry cassette 2, which includes zygotic antidote 2 (Zygotic A2). Cassette 2 also carries a set of flanking genes that can be used to excise Zygotic A2 from the Y chromosome in response to the presence of tetracycline. This is achieved as above, for the X chromosome cassette. However, note that males carrying only the excised version of the <i>Medusa</i> Y chromosome, and no <i>Medusa</i> X chromosome, are dead because they express zygotic T2 but not Zygotic A2. In order to create insects that carry both the excised X cassette and the excised Y cassette, tetracycline-driven excision needs to be done in a context of a cross. B: A stock carrying the non-excised <i>Medusa</i> X and Y chromosomes (MT1–ZA2+R and ZT2–ZA1+R, respectively) is viable and fertile (upper, parental generation). When larvae (before differentiation of gametes) carrying these chromosomes are exposed to tetracycline, FLP-mediated recombination occurs in the germline, generating gametes that carry the excised versions of the <i>Medusa</i> X and Y chromosomes. Male progeny that inherit excised X and Y chromosomes survive because they carry zygotic antidote 2 as well as zygotic toxin 2. They are identified by the fact that they express both RFP and GFP. Female progeny with excised X chromosomes die because the action of maternal toxin 1 in the adult female is unopposed in progeny by zygotic antidote 1. Progeny that inherit non-excised chromosomes will lack GFP or RFP. Large numbers of <i>Medusa</i> males can be sorted away from these using fluorescence-based larval sorting technologies. These are the males used for release.</p>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases"], "article_id"=>1115536, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102694.g005", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generating_Medusa_males_/1115536", "title"=>"Generating <i>Medusa</i> males.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:40:54"}
• {"files"=>["https://ndownloader.figshare.com/files/1606398"], "description"=>"<p>A: Bi-directional migration model in which mosquitoes carrying the <i>Medusa</i> system are introduced into population C, and populations C and D exchange a fraction, <i>m</i>, of their individuals at each generation. B: Confined population suppression following six consecutive releases of 10,000 <i>Medusa</i> males (no fitness cost) into population C (bi-directional migration rate of 1% per generation). Results depicted are a single run of the stochastic simulation. C: Confined population suppression and a wild-type rebound for the same release scenario as in panel B, but a smaller bi-directional migration rate of 0.03% per generation. D: The frequency of a wild-type rebound occurring within 100 generations of a super-threshold release (no <i>Medusa</i> fitness cost) as a function of migration rate. E: Sustained population suppression achieved through regular releases of 180 <i>Medusa</i> males into population C at each generation following six initial releases of 10,000 <i>Medusa</i> males into the same population.</p>", "links"=>[], "tags"=>["agriculture", "Pest control", "Computational biology", "Evolutionary biology", "population genetics", "genetics", "microbiology", "organisms", "animals", "invertebrates", "arthropoda", "insects", "mosquitoes", "Population biology", "Theoretical biology", "epidemiology", "disease vectors", "Vector biology", "Infectious diseases", "partially-isolated"], "article_id"=>1115534, "categories"=>["Biological Sciences"], "users"=>["John M. Marshall", "Bruce A. Hay"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0102694.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Medusa_dynamics_in_two_partially_isolated_populations_/1115534", "title"=>"<i>Medusa</i> dynamics in two partially-isolated populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-23 03:40:54"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime