Keywords: mechanisms

cifB-transcript levels largely explain cytoplasmic incompatibility variation across divergent Wolbachia

J. D. Shropshire, E. Hamant, W. R. Conner and B. S. Cooper,  PNAS Nexus,  2022.
Divergent hosts often associate with intracellular microbes that influence their fitness. Maternally transmitted Wolbachia bacteria are the most common of these endosymbionts due largely to cytoplasmic incompatibility (CI) that kills uninfected embryos fertilized by ...
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Male-killing-associated bacteriophage WO identified from comparisons of Wolbachia endosymbionts of Homona magnanima

H. Arai, H. Anbutsu, Y. Nishikawa, M. Kogawa, K. Ishii, M. Hosokawa, S.-R. Lin, M. Ueda, M. Nakai, Y. Kunimi, T. Harumoto, D. Kageyama, H. Takeyama and M. N. Inoue,  bioRxiv,  2022.
The origin and mechanism of male-killing, an advantageous strategy employed by maternally transmitted symbionts such as Wolbachia, remain unclear. We compared genomes of four Wolbachia strains derived from Homona magnanima, a male-killing strain wHm-t (1.5 Mb), and three ...
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Perplexing dynamics of Wolbachia proteins for cytoplasmic incompatibility

T. Harumoto and T. Fukatsu,  PLOS Biology,  20:e3001644. 2022.
The mechanism of symbiont-induced cytoplasmic incompatibility has been a long-lasting mystery. This Primer explores a new study on Wolbachia’s Cif proteins in PLOS Biology that provides supportive evidence for the “Host-Modification Model,” although the alternative ...
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The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility

R. Kaur, B. A. Leigh, I. T. Ritchie and S. R. Bordenstein,  PLOS Biology,  20:e3001584. 2022.
In Drosophila melanogaster, germline expression of the Wolbachia proteins CifA and CifB causes cytoplasmic incompatibility, but how this impairs male reproduction remains unclear. This study shows how Cif proteins encoded by the endosymbiont prophage invade the fly’s gametic ...
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Expanding the flexibility of genome editing approaches for population control of the malaria mosquito

N. Kranjc,  Imperial College London-PhD,  2022.
Discovery and adaptation of CRISPR-Cas systems for genome editing have allowed us to gain an efficient and yet simple tool for genetic manipulation in various fields of molecular biology and biotechnology. One of the most promising applications is the use of CRISPR-Cas9 ...
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Cytoplasmic incompatibility: A Wolbachia toxin–antidote mechanism comes into view

M. Hochstrasser,  Current Biology,  32:R287-R289. 2022.
The Wolbachia cidA and cidB genes promote bacterial endosymbiont inheritance through the host female germline. CidB is now shown to load into maturing sperm nuclei. Following fertilization, it disrupts paternal chromosome condensation, triggering embryonic arrest if not countered ...
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Differential viral RNA methylation contributes to pathogen blocking in Wolbachia-colonized arthropods

T. Bhattacharya, L. Yan, J. M. Crawford, H. Zaher, I. L. G. Newton and R. W. Hardy,  PLoS Pathogens,  18:e1010393. 2022.
Arthropod endosymbiont Wolbachia pipientis is part of a global biocontrol strategy to reduce the replication of mosquito-borne RNA viruses such as alphaviruses. We previously demonstrated the importance of a host cytosine methyltransferase, DNMT2, in Drosophila and viral RNA as a ...
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Genetic Drive Systems in Nature

David O'Brochta and Hector Quemada,  GeneConvene Global Collaborative,  2022.
Intra genomic genetic conflicts are ubiquitous in nature and have shaped and continue to shape the evolution of plants, animals, and microbes. These conflicts can result in preferential transmission - drive - of genes, various genetic elements, and even whole chromosomes. ...
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Considerations for homology-based DNA repair in mosquitoes: Impact of sequence heterology and donor template source

J. X. D. Ang, K. Nevard, R. Ireland, D.-K. Purusothaman, S. A. N. Verkuijl, L. Shackleford, E. Gonzalez, M. A. E. Anderson and L. Alphey,  PLOS Genetics,  18:e1010060. 2022.
Author summary The field of genetic control of mosquito vectors has progressed rapidly in recent years, especially in Cas9-based control systems, due to its robustness to elicit a species-specific and dispersive control of mosquito population. To generate a Cas9-based ...
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A-to-I mRNA editing controls spore death induced by a fungal meiotic drive gene in homologous and heterologous expression systems

J. M. Lohmar, N. A. Rhoades, T. N. Patel, R. H. Proctor, T. M. Hammond and D. W. Brown,  Genetics,  2022.
Spore killers are meiotic drive elements that can block development of sexual spores in fungi. In the maize ear rot and mycotoxin-producing fungus Fusarium verticillioides, a spore killer called SkK has been mapped to a 102-kb interval of chromosome V. Here, we show that a gene ...
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Paternal transmission of the Wolbachia CidB toxin underlies cytoplasmic incompatibility

B. Horard, K. Terretaz, A. S. Gosselin-Grenet, H. Sobry, M. Sicard, F. Landmann and B. Loppin,  Current Biology,  2022.
Wolbachia are widespread endosymbiotic bacteria that manipulate the reproduction of arthropods through a diversity of cellular mechanisms. In cytoplasmic incompatibility (CI), a sterility syndrome originally discovered in the mosquito Culex pipiens, uninfected eggs fertilized by ...
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A natural fungal gene drive enacts killing through targeting DNA

A. S. Urquhart and D. M. Gardiner,  bioRxiv,  2022.01.19.477016. 2022.
Fungal spore-killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to ...
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From Wolbachia genomics to phenotype: molecular models of cytoplasmic incompatibility must account for the multiplicity of compatibility types

A. Namias, M. Sicard, M. Weill and S. Charlat,  Current Opinion in Insect Science,  2021.
Wolbachia endosymbionts commonly induce cytoplasmic incompatibility, making infected males’ sperm lethal to the embryos unless these are rescued by the same bacterium, inherited from their mother. Causal genes were recently identified but two families of mechanistic models are ...
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Nuclear transport genes recurrently duplicate by means of RNA intermediates in Drosophila but not in other insects

A. Mirsalehi, D. N. Markova, M. Eslamieh and E. Betrán,  BMC Genomics,  22:876. 2021.
We find that most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. We also retrieve many pseudogenes for the Ran gene. Some of the duplicates are relatively young and likely contributing to the ...
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A flurry of sex-ratio distorters

A. A. Vogan,  Nature Ecology and Evolution,  2021.
Two analyses of long-read sequencing show that the Winters sex-ratio distorter of Drosophila has been a part of a recent gene family expansion, coupled to the appearance of suppressors, in a genomic arms race driven by satellite DNA.
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Rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors

J. Vedanayagam, C. J. Lin and E. C. Lai,  Nature Ecology and Evolution,  2021.
Meiotic drivers are a class of selfish genetic elements whose existence is frequently hidden due to concomitant suppressor systems. Accordingly, we know little of their evolutionary breadth and molecular mechanisms. Here, we trace the evolution of the Dox meiotic drive system in ...
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Tubulin post-translational modifications in meiosis

T. Akera,  Seminars in Cell & Developmental Biology,  2021.
Haploid gametes are produced from diploid parents through meiosis, a process inherent to all sexually reproducing eukaryotes. Faithful chromosome segregation in meiosis is essential for reproductive success, although it is less clear how the meiotic spindle achieves this compared ...
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High-resolution in situ analysis of Cas9 germline transcript distributions in gene-drive Anopheles mosquitoes

G. Terradas, A. Hermann, A. A. James, W. McGinnis and E. Bier,  G3-Genes Genomes Genetics,  2021.
Gene drives are programmable genetic elements that can spread beneficial traits into wild populations to aid in vector-borne pathogen control. Two different drives have been developed for population modification of mosquito vectors. The Reckh drive (vasa-Cas9) in Anopheles ...
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Molecular Mechanisms and Evolutionary Consequences of Spore Killers in Ascomycetes

S. Zanders and H. Johannesson,  Microbiology and Molecular Biology Reviews,  2021.
In this review, we examine the fungal spore killers. These are meiotic drive elements that cheat during sexual reproduction to increase their transmission into the next generation. Spore killing has been detected in a number of ascomycete genera, including Podospora, Neurospora, ...
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The supernumerary B chromosome of maize: drive and genomic conflict

J. A. Birchler and H. Yang,  Open Biol,  11:210197. 2021.
The supernumerary B chromosome of maize is dispensable, containing no vital genes, and thus is variable in number and presence in lines of maize. In order to be maintained in populations, it has a drive mechanism consisting of nondisjunction at the pollen mitosis that produces ...
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A Maternal-Effect Toxin Affects Epithelial Differentiation and Tissue Mechanics in Caenorhabditis elegans

C. Lehmann and C. Pohl,  Frontiers in Cell and Developmental Biology,  9. 2021.
Selfish genetic elements that act as post-segregation distorters cause lethality in non-carrier individuals after fertilization. Two post-segregation distorters have been previously identified in Caenorhabditis elegans, the peel-1/zeel-1 and the sup-35/pha-1 elements. These ...
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Novel Symbiotic Genome-Scale Model Reveals Wolbachia’s Arboviral Pathogen Blocking Mechanism in Aedes aegypti

N. E. Jiménez, Z. P. Gerdtzen, Á. Olivera-Nappa, J. C. Salgado and C. Conca,  mBio,  e0156321. 2021.
Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of Wolbachia as an approach for disease control has motivated new research related to ...
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Structural and mechanistic insights into the complexes formed by Wolbachia cytoplasmic incompatibility factors

Y. Xiao, H. Chen, H. Wang, M. Zhang, X. Chen, J. M. Berk, L. Zhang, Y. Wei, W. Li, W. Cui, F. Wang, Q. Wang, C. Cui, T. Li, C. Chen, S. Ye, L. Zhang, X. Ji, J. Huang, W. Wang, Z. Wang, M. Hochstrasser and H. Yang,  Proceedings of the National Academy of Sciences,  118. 2021.
Wolbachia bacteria, inherited through the female germ line, infect a large fraction of arthropod species. Many Wolbachia strains manipulate host reproduction, most commonly through cytoplasmic incompatibility (CI). CI, a conditional male sterility, results when Wolbachia-infected ...
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Sexual selection can partly explain low frequencies of Segregation Distorter alleles

T. A. Keaney, T. M. Jones and L. Holman,  Proceedings of the Royal Society B: Biological Sciences,  288:20211190. 2021.
The Segregation Distorter (SD) allele found in Drosophila melanogaster distorts Mendelian inheritance in heterozygous males by causing developmental failure of non-SD spermatids, such that greater than 90% of the surviving sperm carry SD. This within-individual advantage should ...
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A single mutation weakens symbiont-induced reproductive manipulation through reductions in deubiquitylation efficiency

J. F. Beckmann, K. Van Vaerenberghe, D. E. Akwa and B. S. Cooper,  Proceedings of the National Academy of Sciences,  118:e2113271118. 2021.
We show that a single naturally observed mutation weakens CI by reducing deubiquitylation. These discoveries help elucidate the molecular basis of symbiont-induced reproductive manipulations.Animals interact with microbes that affect their performance and fitness, including ...
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Diverse wMel variants of Wolbachia pipientis differentially rescue fertility and cytological defects of the bag of marbles partial loss of function mutation in Drosophila melanogaster

J. E. Bubnell, P. Fernandez-Begne, C. K. S. Ulbing and C. F. Aquadro,  G3 Genes|Genomes|Genetics,  2021.
In Drosophila melanogaster, the maternally inherited endosymbiont Wolbachia pipientis interacts with germline stem cell genes during oogenesis. One such gene, bag of marbles (bam) is the key switch for differentiation and also shows signals of adaptive evolution for protein ...
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Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes

F. Pajpach, T. Wu, L. Shearwin-Whyatt, K. Jones and F. Grützner,  Genes,  12. 2021.
Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid ...
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A CRISPR endonuclease gene drive reveals two distinct mechanisms of inheritance bias

S. A. N. Verkuijl, E. González, J. X. D. Ang, M. Li, N. P. Kandul, M. Anderson, O. S. Akbari, M. Bonsall and L. Alphey,  bioRxiv,  2020.12.15.421271. 2020.
In this study, we report the functioning of sds3, bgcn, and nup50 expressed Cas9 in an Aedes aegypti homing split drive system targeting the white gene. We report their inheritance biasing capability, propensity for maternal deposition, and zygotic/somatic expression. ...
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Gene drive blocks malaria transmission in mosquitoes

labonline,  labonline,  2020.
Employing a strategy known as ‘population modification’, which involves using a CRISPR-Cas9 gene drive system to introduce genes preventing parasite transmission into mosquito chromosomes, University of California (UC) researchers have made a major advance in the use of ...
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A gene-drive rescue system for the modification of malaria mosquito populations

A. Adolfi,  Nature Research Bioengineering Community,  2020.
Mosquito populations can now be reliably modified using 1) antimalarial molecules that block parasite development and 2) a CRISPR-based gene drive system that mediates their rapid spreading across the vector population.
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UC researchers pioneer more effective method of blocking malaria transmission in mosquitoes

UCI,  UCI News,  2020.
University of California, Irvine postdoctoral researcher Adriana Adolfi, in collaboration with colleagues at UCI, UC Berkeley and UC San Diego, followed up on the group’s pioneering effort to develop CRISPR-based gene drive systems for making mosquito vectors resistant to ...
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Efficient population modification gene-drive rescue system in the malaria mosquito Anopheles stephensi

A. Adolfi, V. M. Gantz, N. Jasinskiene, H.-F. Lee, K. Hwang, G. Terradas, E. A. Bulger, A. Ramaiah, J. B. Bennett, J. J. Emerson, J. M. Marshall, E. Bier and A. A. James,  Nature Communications,  11:5553. 2020.
Here, we develop a recoded gene-drive rescue system for population modification of the malaria vector, Anopheles stephensi, that relieves the load in females caused by integration of the drive into the kynurenine hydroxylase gene by rescuing its function. Non-functional resistant ...
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Cellular mechanisms regulating synthetic sex ratio distortion in the Anopheles gambiae germline

R. E. Haghighat-Khah, A. Sharma, M. R. Wunderlich, G. Morselli, L. A. Marston, C. Bamikole, A. Hall, N. Kranjc, C. Taxiarchi, I. Sharakhov and R. Galizi,  Pathogens and Global Health,  114:370-378. 2020.
Meiotic cleavage of rDNA repeats, located in the sex chromosomes of A. gambiae SD males, affects the competitiveness of mature sperm to fertilize the female oocyte.
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Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

R. Carballar-Lejarazú, C. Ogaugwu, T. Tushar, A. Kelsey, T. B. Pham, J. Murphy, H. Schmidt, Y. Lee, G. C. Lanzaro and A. A. James,  Proceedings of the National Academy of Sciences,  202010214. 2020.
We show here that the Cas9/guide RNA-based gene-drive components of a genetically-engineered malaria mosquito vector, Anopheles gambiae, achieve key target product profile requirements for efficacy and performance.
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Mixed knobs in corn cobs

P. Lamelza and M. A. Lampson,  Genes and Development,  34:1110-1112. 2020.
In this issue of Genes & Development, Swentowsky and colleagues (pp. 1239-1251) show that two types of knobs, those composed of 180-bp and TR1 sequences, recruit their own novel and divergent kinesin-14 family members to form neocentromeres.
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Distinct kinesin motors drive two types of maize neocentromeres

K. W. Swentowsky, J. I. Gent, E. G. Lowry, V. Schubert, X. Ran, K. F. Tseng, A. E. Harkess, W. H. Qiu and R. K. Dawe,  Genes and Development,  34:1239-1251. 2020.
Here we describe a second kinesin-14 gene, TR-1 kinesin (Trkin), that is required to mobilize neocentromeres made up of the minor tandem repeat TR-1.
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Vector genetics, insecticide resistance and gene drives: An agent-based modeling approach to evaluate malaria transmission and elimination

P. Selvaraj, E. A. Wenger, D. Bridenbecker, N. Windbichler, J. R. Russell, J. Gerardin, C. A. Bever and M. Nikolov,  PloS Computational Biology,  16:21. 2020.
Here, we investigate the reduced efficacy of current vector control measures in the presence of insecticide resistance and evaluate the likelihood of achieving local malaria elimination using gene drive mosquitoes released into a high transmission setting alongside other vector ...
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Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers

M. A. Bravo Núñez, I. M. Sabbarini, L. E. Eide, R. L. Unckless and S. E. Zanders,  eLife,  9:e57936. 2020.
Here, we demonstrate that in scenarios analogous to outcrossing, wtf drivers generate a fitness landscape in which atypical spores, such as aneuploids and diploids, are advantageous. In this context, wtf drivers can decrease the fitness costs of mutations that disrupt meiotic ...
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CRISPR gene drives could eliminate many vector-driven pests and diseases, but challenges remain

J. Champer,  Genetic Literacy Project,  2020.
A functioning gene drive system could fundamentally change our strategies for the control of vector-borne diseases by facilitating rapid dissemination of transgenes that prevent pathogen transmission or reduce vector capacity. CRISPR/Cas9 gene drive promises such a mechanism, ...
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Extensive Recombination Suppression and Epistatic Selection Causes Chromosome-Wide Differentiation of a Selfish Sex Chromosome in Drosophila pseudoobscura

Z. L. Fuller, S. A. Koury, C. J. Leonard, R. E. Young, K. Ikegami, J. Westlake, S. Richards, S. W. Schaeffer and N. Phadnis,  Genetics,  216:205. 2020.
Here, we conduct a multifaceted study of the multiply inverted Drosophila pseudoobscura SR chromosome to understand the evolutionary history, genetic architecture, and present-day dynamics that shape this enigmatic selfish chromosome.
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Artificial Selection Finds New Hypotheses for the Mechanism of Wolbachia-Mediated Dengue Blocking in Mosquitoes

S. A. Ford, I. Albert, S. L. Allen, S. F. Chenoweth, M. Jones, C. Koh, A. Sebastian, L. T. Sigle and E. A. McGraw,  Frontiers in Microbiology,  11:1456. 2020.
We recently used experimental evolution to reveal that Wolbachia-mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation ...
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Split-gene drive system provides flexible application for safe laboratory investigation and potential field deployment

V. L. Del Amo, A. L. Bishop, H. M. Sánchez C, J. B. Bennett, X. Feng, J. M. Marshall, E. Bier and V. M. Gantz,  bioRxiv,  684597. 2019.
CRISPR-based gene drives spread through populations bypassing the dictates of Mendelian genetics, offering a population-engineering tool for tackling vector-borne diseases, managing crop pests, and helping island conservation efforts; unfortunately, current technologies raise ...
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CRISPR in Parasitology: Not Exactly Cut and Dried!

Bryant, JMB, S.; Glover, L.; Hutchinson, S.; Rachidi, N.,  Trends in Parasitology,  35:409-422. 2019.
CRISPR/Cas9 technology has been developing rapidly in the field of parasitology, allowing for the dissection of molecular processes with unprecedented efficiency. Optimization and implementation of a new technology like CRISPR, especially in nonmodel organisms, requires ...
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Gene drive to reduce malaria transmission in sub-Saharan Africa

A. Burt, M. Coulibaly, A. Crisanti, A. Diabate and J. K. Kayondo,  Journal of Responsible Innovation,  5:S66-S80. 2018.
Gene drive is a natural process by which some genes are inherited at a greater-than-Mendelian rate and can spread through a population even if they cause harm to the organisms carrying them. Many different synthetic gene drive systems have been proposed to suppress the number of ...
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Trojan Females and Judas Goats: Evolutionary Traps as Tools in Wildlife Management

B. A. Robertson, R. S. Ostfeld and F. Keesing,  Bioscience,  67:982-993. 2017.
Here, we bring together science from the pest-control, eco-evolutionary, and conservation communities to outline how evolutionary traps can be repurposed to eliminate or control pest species. We highlight case studies and devise strategies for the selection of appropriate cues to ...
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Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread

J. Min, C. Noble, D. Najjar and K. M. Esvelt,  bioRxiv,  104877. 2017.
Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered ‘daisy’ sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene ...
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What’s a Gene Drive? And what are the risks and benefits?

Risk Bites,  Arizona State University,  2015.
This video uses ‘white board cartooning’ as a means of illustrating concepts.
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Gene Drive

Wyss Institute,  Harvard University,  2014.
This short video produced by the Wyss Institute and Harvard School of Public Health illustrates in very basic terms the concept of gene drive as distorted patterns of inheritance.
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Site-specific selfish genes as tools for the control and genetic engineering of natural populations

Burt, A,  Proceedings of the Royal Society B-Biological Sciences,  270:921-928. 2003.
Site-specific selfish genes exploit host functions to copy themselves into a defined target DNA sequence, and include homing endonuclease genes, group II introns and some LINE-like transposable elements. If such genes can be engineered to target new host sequences, then they can ...
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