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Open accessJournal ArticleDOI: 10.1038/S41598-021-83239-4

Novel combination of CRISPR-based gene drives eliminates resistance and localises spread.

04 Mar 2021-Scientific Reports (Springer Science and Business Media LLC)-Vol. 11, Iss: 1, pp 1-15
Abstract: Invasive species are among the major driving forces behind biodiversity loss. Gene drive technology may offer a humane, efficient and cost-effective method of control. For safe and effective deployment it is vital that a gene drive is both self-limiting and can overcome evolutionary resistance. We present HD-ClvR in this modelling study, a novel combination of CRISPR-based gene drives that eliminates resistance and localises spread. As a case study, we model HD-ClvR in the grey squirrel (Sciurus carolinensis), which is an invasive pest in the UK and responsible for both biodiversity and economic losses. HD-ClvR combats resistance allele formation by combining a homing gene drive with a cleave-and-rescue gene drive. The inclusion of a self-limiting daisyfield gene drive allows for controllable localisation based on animal supplementation. We use both randomly mating and spatial models to simulate this strategy. Our findings show that HD-ClvR could effectively control a targeted grey squirrel population, with little risk to other populations. HD-ClvR offers an efficient, self-limiting and controllable gene drive for managing invasive pests.

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Topics: Gene Drive Technology (66%), Gene drive (66%), Population (52%)
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7 results found


Open accessJournal ArticleDOI: 10.1186/S12862-021-01881-Y
09 Aug 2021-
Abstract: BACKGROUND Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators' point of view. We address this concern by defining a simplified parameter based language of synthetic drives. RESULTS Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. CONCLUSION Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.

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Topics: Gene drive (59%), Population (51%), Evolutionary dynamics (50%)

2 Citations


Open accessPosted ContentDOI: 10.1101/2021.04.30.442149
30 Apr 2021-bioRxiv
Abstract: Varroa mites (Varroa destructor) are the most significant threat to beekeeping worldwide. They are directly or indirectly responsible for millions of colony losses each year. Beekeepers are somewhat able to control Varroa populations through the use of physical and chemical treatments. However, these methods range in effectiveness, can harm honey bees, can be physically demanding on the beekeeper, and do not always provide complete protection from Varroa. More importantly, in some populations Varroa mites have developed resistance to available acaricides. Overcoming the Varroa mite problem will require novel and targeted treatment options. Here, we explore the potential of gene drive technology to control Varroa. We show that spreading a neutral gene drive in Varroa is possible but requires specific colony-level management practices to overcome the challenges of both inbreeding and haplodiploidy. Furthermore, continued treatment with acaricides is necessary to give a gene drive time to fix in the Varroa population. Unfortunately, a gene drive that impacts female or male fertility does not spread in Varroa. Therefore, we suggest that the most promising way forward is to use a gene drive which carries a toxin precursor or removes acaricide resistance alleles.

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Topics: Varroa destructor (69%), Varroa (69%), Gene drive (52%) ... show more

1 Citations


Open accessJournal ArticleDOI: 10.1371/JOURNAL.PGEN.1009792
18 Oct 2021-PLOS Genetics
Abstract: The transformer (tra) gene is essential for female development in many insect species, including the Australian sheep blow fly, Lucilia cuprina. Sex-specific tra RNA splicing is controlled by Sex lethal (Sxl) in Drosophila melanogaster but is auto-regulated in L. cuprina. Sxl also represses X chromosome dosage compensation in female D. melanogaster. We have developed conditional Lctra RNAi knockdown strains using the tet-off system. Four strains did not produce females on diet without tetracycline and could potentially be used for genetic control of L. cuprina. In one strain, which showed both maternal and zygotic tTA expression, most XX transformed males died at the pupal stage. RNAseq and qRT-PCR analyses of mid-stage pupae showed increased expression of X-linked genes in XX individuals. These results suggest that Lctra promotes somatic sexual differentiation and inhibits X chromosome dosage compensation in female L. cuprina. However, XX flies homozygous for a loss-of-function Lctra knockin mutation were fully transformed and showed high pupal eclosion. Two of five X-linked genes examined showed a significant increase in mRNA levels in XX males. The stronger phenotype in the RNAi knockdown strain could indicate that maternal Lctra expression may be essential for initiation of dosage compensation suppression in female embryos.

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Topics: Dosage compensation (57%), Lucilia cuprina (56%), Gene knockdown (52%) ... show more

Open accessBook ChapterDOI: 10.1016/B978-0-12-822562-2.00016-5
01 Jan 2021-
Topics: Genome editing (64%)


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55 results found


Open accessJournal ArticleDOI: 10.1126/SCIENCE.1231143
Le Cong1, Le Cong2, F. Ann Ran2, F. Ann Ran1  +12 moreInstitutions (5)
15 Feb 2013-Science
Abstract: Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.

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Topics: CRISPR/Cpf1 (72%), CRISPR (66%), Transcription activator-like effector nuclease (66%) ... show more

10,364 Citations


Journal ArticleDOI: 10.1126/SCIENCE.287.5459.1770
Osvaldo E. Sala1, F. S. Chapin2, Juan J. Armesto3, Eric L. Berlow4  +15 moreInstitutions (14)
10 Mar 2000-Science
Abstract: Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably will have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.

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Topics: Global biodiversity (63%), Land use, land-use change and forestry (62%), Biodiversity (59%) ... show more

7,686 Citations


Journal ArticleDOI: 10.1126/SCIENCE.1067081
Carlos Lois1, Elizabeth J. Hong1, Shirley Pease1, Eric J. Brown1  +1 moreInstitutions (1)
01 Feb 2002-Science
Abstract: Single-cell mouse embryos were infected in vitro with recombinant lentiviral vectors to generate transgenic mice carrying the green fluorescent protein (GFP) gene driven by a ubiquitously expressing promoter. Eighty percent of founder mice carried at least one copy of the transgene, and 90% of these expressed GFP at high levels. Progeny inherited the transgene(s) and displayed green fluorescence. Mice generated using lentiviral vectors with muscle-specific and T lymphocyte–specific promoters expressed high levels of GFP only in the appropriate cell types. We have also generated transgenic rats that express GFP at high levels, suggesting that this technique can be used to produce other transgenic animal species.

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Topics: Green fluorescent protein (55%), Transgene (54%)

1,968 Citations


Journal ArticleDOI: 10.1016/J.TREE.2009.03.016
Liba Pejchar1, Harold A. Mooney2Institutions (2)
Abstract: Although the effects of invasive alien species (IAS) on native species are well documented, the many ways in which such species impact ecosystem services are still emerging. Here we assess the costs and benefits of IAS for provisioning, regulating and cultural services, and illustrate the synergies and tradeoffs associated with these impacts using case studies that include South Africa, the Great Lakes and Hawaii. We identify services and interactions that are the least understood and propose a research and policy framework for filling the remaining knowledge gaps. Drawing on ecology and economics to incorporate the impacts of IAS on ecosystem services into decision making is key to restoring and sustaining those life-support services that nature provides and all organisms depend upon.

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Topics: Ecosystem services (63%)

957 Citations


Open accessJournal ArticleDOI: 10.1093/NAR/GKY1085
Abstract: eggNOG is a public database of orthology relationships, gene evolutionary histories and functional annotations. Here, we present version 5.0, featuring a major update of the underlying genome sets, which have been expanded to 4445 representative bacteria and 168 archaea derived from 25 038 genomes, as well as 477 eukaryotic organisms and 2502 viral proteomes that were selected for diversity and filtered by genome quality. In total, 4.4M orthologous groups (OGs) distributed across 379 taxonomic levels were computed together with their associated sequence alignments, phylogenies, HMM models and functional descriptors. Precomputed evolutionary analysis provides fine-grained resolution of duplication/speciation events within each OG. Our benchmarks show that, despite doubling the amount of genomes, the quality of orthology assignments and functional annotations (80% coverage) has persisted without significant changes across this update. Finally, we improved eggNOG online services for fast functional annotation and orthology prediction of custom genomics or metagenomics datasets. All precomputed data are publicly available for downloading or via API queries at http://eggnog.embl.de.

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Topics: Genomics (51%), Metagenomics (50%)

744 Citations


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20217