Keywords: Toxin-antidote
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Cleave and Rescue gamete killers create conditions for gene drive in plantsO. Georg, L. J. Michelle, I. Tobin and A. H. Bruce, bioRxiv, 2023.10.13.562303. 2023.
Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a ... |
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Overriding Mendelian inheritance in Arabidopsis with a CRISPR toxin-antidote gene drive that impairs pollen germinationL. Yang, J. Bingke, C. Jackson and Q. Wenfeng, bioRxiv, 2023.10.10.561637. 2023.
Synthetic gene drives, inspired by natural selfish genetic elements, present transformative potential for disseminating traits that benefit humans throughout wild populations, irrespective of potential fitness costs. Here, we constructed a gene drive system called CRISPR-Assisted ... |
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A natural gene drive element confers speciation in riceY. Li, S. Liu and R. Shen, Chinese Science Bulletin, 68:3400-3402. 2023.
For a long time, although many important advances have been made in the field of rice hybrid sterility, the specific molecular mechanism behind the "killer-protector"/ "poison-antidote" model has been unclear. Recently, the team of Academician Wan Jianmin of Nanjing Agricultural ... |
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Proliferation and dissemination of killer meiotic drive lociE. C. Lai and A. A. Vogan, Current Opinion in Genetics and Development, 82:102100. 2023.
Killer meiotic drive elements are selfish genetic entities that manipulate the sexual cycle to promote their own inheritance via destructive means. Two broad classes are sperm killers, typical of animals and plants, and spore killers, which are present in ascomycete fungi. Killer ... |
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A natural gene drive system confers reproductive isolation in riceC. Wang, J. Wang, J. Lu, Y. Xiong, Z. Zhao, X. Yu, X. Zheng, J. Li, Q. Lin, Y. Ren, Y. Hu, X. He, C. Li, Y. Zeng, R. Miao, M. Guo, B. Zhang, Y. Zhu, Y. Zhang, W. Tang, Y. Wang, B. Hao, Q. Wang, S. Cheng, X. He, B. Yao, J. Gao, X. Zhu, H. Yu, Y. Wang, Y. S, Cell, 2023.
Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two ... |
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Modeling emergence of Wolbachia toxin-antidote protein functions with an evolutionary algorithmJ. Beckmann, J. Gillespie and D. Tauritz, Front Microbiol, 14:1116766. 2023.
Evolutionary algorithms (EAs) simulate Darwinian evolution and adeptly mimic natural evolution. Most EA applications in biology encode high levels of abstraction in top-down population ecology models. In contrast, our research merges protein alignment algorithms from ... |
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Modelling Emergence of Wolbachia Toxin-Antidote Protein Functions with an Evolutionary AlgorithmJ. Beckmann, J. Gillespie and D. Tauritz, bioRxiv, 2023.
Evolutionary algorithms (EAs) simulate Darwinian evolution and adeptly mimic natural evolution. Most EA applications in biology encode high levels of abstraction in top-down ecological population models. In contrast, our research merges protein alignment algorithms from ... |
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Convergent Aedes and Drosophila CidB interactomes suggest cytoplasmic incompatibility targets are conservedS. O. Oladipupo, J. D. Carroll and J. F. Beckmann, Insect Biochem Mol Biol, 103931. 2023.
Wolbachia-mediated cytoplasmic incompatibility (CI) is a conditional embryonic lethality induced when Wolbachia-modified sperm fertilizes an uninfected egg. The Wolbachia proteins, CidA and CidB control CI. CidA is a rescue factor that reverses lethality. CidA binds to CidB. CidB ... |
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A toxin-antidote CRISPR gene drive system for regional population modificationJ. Champer, E. Lee, E. Yang, C. Liu, A. G. Clark and P. W. Messer, Nature Communications, 11:1082. 2023.
Engineered gene drives based on a homing mechanism could rapidly spread genetic alterations through a population. However, such drives face a major obstacle in the form of resistance against the drive. In addition, they are expected to be highly invasive. Here, we introduce the ... |
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Simulations Reveal High Efficiency and Confinement of a Population Suppression CRISPR Toxin-Antidote Gene DriveY. Zhu and J. Champer, ACS Synthetic Biolog, 2023.
Though engineered gene drives hold great promise for spreading through and suppressing populations of disease vectors or invasive species, complications such as resistance alleles and spatial population structure can prevent their success. Additionally, most forms of suppression ... |
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Assessment of distant-site rescue elements for CRISPR toxin-antidote gene drivesJ. Chen, X. Xu and J. Champer, bioRxiv, 2023.01.06.522951. 2023.
New types of gene drives promise to provide increased flexibility, offering many options for confined modification or suppression of target populations. Among the most promising are CRISPR toxin-antidote gene drives, which disrupt essential wild-type genes by targeting them with ... |
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Performance characteristics allow for confinement of a CRISPR toxin-antidote gene drive designed for population suppressionS. Zhang and J. Champer, bioRxiv, 2022.12.13.520356. 2022.
Gene drives alleles that can bias their own inheritance are a promising way to engineer populations for control of disease vectors, invasive species, and agricultural pests. Recent advancements in the field have yielded successful examples of powerful suppression type drives and ... |
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How selfish genes succeedStowers Institute for Medical Research, ScienceDaily, 2022.
A new study reveals how a selfish gene in yeast uses a poison-antidote strategy that enables its function and likely has facilitated its long-term evolutionary success. This strategy is an important addition for scientists studying similar systems including teams that are ... |
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S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic driveN. L. Nuckolls, A. Nidamangala Srinivasa, A. C. Mok, R. M. Helston, M. A. Bravo Núñez, J. J. Lange, T. J. Gallagher, C. W. Seidel and S. E. Zanders, PLOS Genetics, 18:e1009847. 2022.
Author summary Genomes are often considered a collection of ‘good’ genes that provide beneficial functions for the organism. From this perspective, disease is thought to arise due to disfunction of ‘good’ genes. For example, infertility can be caused by the failure of a ... |
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Gene drive by Fusarium SKC1 is dependent on its competing alleleJ. M. Lohmar, N. A. Rhoades, T. M. Hammond and D. W. Brown, Fungal Genetics and Biology, 163:103749. 2022.
The Fusarium verticillioides SKC1 gene driver is transmitted to offspring in a biased manner through spore killing. The mechanism that allows SKC1 to kill non-SKC1 offspring while sparing others is poorly understood. Here we report that gene drive by SKC1 is dependent on SKC1's ... |
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A Toxin-Antidote Selfish Element Increases Fitness of its HostL. Long, W. Xu, A. B. Paaby and P. T. McGrath, bioRxiv, 2022.07.15.500229. 2022.
Selfish genetic elements can promote their transmission at the expense of individual survival, creating conflict between the element and the rest of the genome. Recently, a large number of toxin-antidote (TA) post-segregation distorters have been identified in non-obligate ... |
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Perplexing dynamics of Wolbachia proteins for cytoplasmic incompatibilityT. 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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Gene drive escape from resistance depends on mechanism and ecologyF. Cook, J. J. Bull and R. Gomulkiewicz, Evolutionary Applications, 2022.
Abstract Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether antidrive resistance will evolve ... |
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Propagation of seminal toxins through binary expression gene drives could suppress populationsJ. Hurtado, S. Revale and L. M. Matzkin, Scientific Reports, 12:6332. 2022.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this ... |
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Cytoplasmic incompatibility: A Wolbachia toxin–antidote mechanism comes into viewM. 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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A-to-I mRNA editing controls spore death induced by a fungal meiotic drive gene in homologous and heterologous expression systemsJ. 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 incompatibilityB. 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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Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in DrosophilaG. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 118:e2107413118. 2021.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise ... |
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Propagation of seminal toxins through binary expression gene drives can suppress polyandrous populationsJ. Hurtado, S. Revale and L. M. Matzkin, bioRxiv, 2021.11.23.469777. 2021.
Gene drives can be highly effective in controlling a target population by disrupting a female fertility gene. To spread across a population, these drives require that disrupted alleles be largely recessive so as not to impose too high of a fitness penalty. We argue that this ... |
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Molecular Mechanisms and Evolutionary Consequences of Spore Killers in AscomycetesS. 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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A Maternal-Effect Toxin Affects Epithelial Differentiation and Tissue Mechanics in Caenorhabditis elegansC. 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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Evolutionary robustness of killer meiotic drivesP. G. Madgwick and J. B. Wolf, Evolution Letters, 2021.
A meiotic driver is a selfish genetic element that interferes with the process of meiosis to promote its own transmission. The most common mechanism of interference is gamete killing, where the meiotic driver kills gametes that do not contain it. A killer meiotic driver is ... |
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Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in DrosophilaG. Oberhofer, B. Hay and T. Ivy, bioRxiv, 2021.07.03.451005. 2021.
One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise ... |
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Selfish gene leaves bacteria behindA. York, Nature Reviews Microbiology, 2021.
Mitochondrial genome evolution is characterized by functional streamlining and gene loss, and gain-of-function gene transfers into the mitochondrial genome are considered rare events. Milner, et al. identified a functional restriction modification (R-M) system in the ... |
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A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protistD. A.-O. Milner, J. A.-O. Wideman, C. A.-O. Stairs, C. D. Dunn and T. A.-O. Richards, PLoS Biology, 2021.
The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss. Therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but ... |
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Gene-Editing Approach To Control the Invasive Gray SquirrelM. Campbell, Technology Networks, 2021.
Biodiversity refers to the extent of the variety of life that is found on planet Earth – and it is currently under threat. Changes in biodiversity have been flagged as "surpassing safe limits" for several years, and world leaders and scientists across the globe are consequently ... |
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Ecology: Gene drives may help control invasive grey squirrel in the UKA. Korn, EurekaAlert, 2021.
Gene drives introduce genes into a population that have been changed to induce infertility in females, allowing for the control of population size. However, they face technical challenges, such as controlling the spread of altered genes as gene drive individuals mate with wild ... |
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Genetically modified squirrels could curb growing population of greysS. Knapton, Telegraph, 2021.
Mutant grey squirrels, genetically modified to spread infertility genes, could be released into the wild to tackle the burgeoning population, |
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Expert reaction to a paper suggesting that gene drives could be used to help control grey squirrel numbers in the UKAnonymous, Science Media Centre, 2021.
This study assesses the prospects for using a gene drive to control invasive grey squirrels in the UK. This is a modelling study exploring the potential for such an approach – no such gene drives currently exist and developing them for grey squirrels would be quite a long-term ... |
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CRISPR gene drives may come to a squirrel near you.Anonymous, NewsBeezer, 2021.
Today’s gene drive technologies could be blended to provide control of the invasive gray squirrel population in the UK – with minimal risk to other populations, according to a new modeling published in the journal Scientific reports. Gene driving introduces altered genes ... |
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Novel combination of CRISPR-based gene drives eliminates resistance and localises spreadN. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc, Scientific Reports, 11:3719. 2021.
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 ... |
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Split versions of Cleave and Rescue selfish genetic elements for measured self limiting gene driveG. Oberhofer, T. Ivy and B. A. Hay, PLoS genetics, 17:e1009385. 2021.
Self-sustaining Cleave and Rescue (ClvR) elements include a DNA sequence-modifying enzyme such as Cas9/gRNAs that disrupts endogenous versions of an essential gene, a tightly linked recoded version of the essential gene resistant to cleavage (the Rescue), and a Cargo. ClvR ... |
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Selfing is the safest sex for Caenorhabditis tropicalisL. M. Noble, J. Yuen, L. Stevens, N. D. Moya, R. Persaud, M. Moscatelli, J. L. Jackson, G. Zhang, R. Chitrakar, L. R. Baugh, C. Braendle, E. C. Andersen, H. S. Seidel and M. V. Rockman, eLife, 10:e62587. 2021.
We generated a chromosomal-scale genome for C. tropicalis and surveyed global diversity. Population structure is very strong, and islands of extreme divergence punctuate a genomic background that is highly homogeneous around the globe. Outbreeding depression in the laboratory is ... |
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Ubiquitous Selfish Toxin-Antidote Elements in Caenorhabditis SpeciesE. Ben-David, P. Pliota, S. A. Widen, A. Koreshova, T. Lemus-Vergara, P. Verpukhovskiy, S. Mandali, C. Braendle, A. Burga and L. Kruglyak, Current Biology, 2021.
Here, we report the discovery of maternal-effect TAs in both C. tropicalis and C. briggsae, two distant relatives of C. elegans. In C. tropicalis, multiple TAs combine to cause a striking degree of intraspecific incompatibility: five elements reduce the fitness of >70% of the ... |
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Evading resistance to gene drivesR. Gomulkiewicz, M. L. Thies and J. J. Bull, bioRxiv, 2020.08.27.270611. 2020.
Our analyses suggest that among gene drives that cause moderate suppression, toxin-antidote systems are less apt to select for resistance than homing drives. Single drives of moderate effect might cause only moderate population suppression, but multiple drives (perhaps delivered ... |
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drivesJ. Champer, S. E. Champer, I. K. Kim, A. G. Clark and P. W. Messer, Evolutionary Applications, 18. 2020.
We model drives which target essential genes that are either haplosufficient or haplolethal, using nuclease promoters with expression restricted to the germline, promoters that additionally result in cleavage activity in the early embryo from maternal deposition, and promoters ... |
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Split drive killer-rescue provides a novel threshold-dependent gene driveM. P. Edgington, T. Harvey-Samuel and L. Alphey, Scientific Reports, 10. 2020.
Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given ... |
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A CRISPR homing gene drive targeting a haplolethal gene removes resistance alleles and successfully spreads through a cage populationJ. Champer, E. Yang, E. Lee, J. Liu, A. G. Clark and P. W. Messer, Proceedings of the National Academy of Sciences, 202004373. 2020.
Here, we present a CRISPR homing drive that was able to successfully spread to all individuals in a laboratory cage study in Drosophila melanogaster without any apparent evolution of resistance. |
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Novel combination of CRISPR-based gene drives eliminates resistance and localises spreadN. R. Faber, G. R. McFarlane, R. C. Gaynor, I. Pocrnic, C. B. A. Whitelaw and G. Gorjanc, bioRxiv, 2020.
We present HD-ClvR, 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 ... |
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Survival of the fit-ishStowers Institute for Medical Research, Science Daily, 2020.
In a paper published online August 13, 2020, in eLife, members of the Zanders lab explain how it could be possible that meiotic drivers persist in the population, even as they kill off many would-be hosts. It turns out that S. pombe can employ variants of other genes to help ... |
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Ubiquitous selfish toxin-antidote elements in Caenorhabditis speciesE. Ben-David, P. Pliota, S. A. Widen, A. Koreshova, T. Lemus-Vergara, P. Verpukhovskiy, S. Mandali, C. Braendle, A. Burga and L. Kruglyak, bioRxiv, 2020.08.06.240564. 2020.
We discovered five maternal-effect Toxin/Antidotes (TAs) in the nematode Caenorhabditis tropicalis and one in C. briggsae. Unlike previously reported TAs, five of these novel toxins do not kill embryos but instead cause larval arrest or developmental delay. Our results show ... |
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Selfing is the safest sex for Caenorhabditis tropicalisL. M. Noble, J. Yuen, L. Stevens, N. Moya, R. Persaud, M. Moscatelli, J. Jackson, C. Braendle, E. C. Andersen, H. S. Seidel and M. V. Rockman, bioRxiv, 2020.08.07.242032. 2020.
Frequent selfing in Caenorhabditis. tropicalis may be a strategy to avoid gene drive-mediated outbreeding depression. Mating systems have profound effects on genetic diversity and compatibility. Caenorhabditis tropicalis is the least genetically diverse among 3 species of ... |
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The Biochemistry of Cytoplasmic Incompatibility Caused by Endosymbiotic BacteriaH. Chen, M. Zhang and M. Hochstrasser, Genes, 11. 2020.
Many species of arthropods carry maternally inherited bacterial endosymbionts that can influence host sexual reproduction to benefit the bacterium. The most well-known of such reproductive parasites is Wolbachia pipientis. Wolbachia are obligate intracellular ... |
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Maternal effect killing by a supergene controlling ant social organizationA. Avril, J. Purcell, S. Béniguel and M. Chapuisat, Proceedings of the National Academy of Sciences, 2020.
Supergenes are clusters of linked loci producing complex alternative phenotypes. In a series of experiments, we demonstrate that a supergene controlling ant social organization distorts Mendel’s laws to enhance its transmission to adult offspring. One supergene haplotype is ... |
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Meiotic driveA. N. Srinivasa and S. E. Zanders, Current Biology, 30:R627-R629. 2020.
What is meiotic drive? Diploid organisms, like you, have two copies of each autosomal chromosome, one from each parent. Sometimes organisms are heterozygous at a given region, meaning they carry different copies (or alleles) of the DNA sequence on the two homologous chromosomes. ... |
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The Enterprise: A massive transposon carrying Spokt meiotic drive genesA. A. Vogan, S. L. Ament-Velásquez, E. Bastiaans, O. Wallerman, S. J. Saupe, A. Suh and H. Johannesson, bioRxiv, 2020.03.25.007153. 2020.
Previously, we described a large genomic feature called the Spok block which is notable due to the presence of meiotic drive genes of the Spok gene family. The Spok block ranges from 110 kb to 247 kb and can be present in at least four different genomic locations within P. ... |
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Genetic Biocontrol – An OverviewGeneConvene Global Collaborative,, GeneConvene Global Collaborative, 2020.This video explains what genetic biocontrol is and surveys various technologies that can be consider genetic biocontrol technologies. It offers a conceptual organization of the various technologies based on the potential of genetic biocontrol organisms to persist and spread in ... |
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Development and testing of a novel killer–rescue self-limiting gene drive system in Drosophila melanogasterS. H. Webster, M. R. Vella and M. J. Scott, Proceedings of the Royal Society B: Biological Sciences, 287:20192994. 2020.
Here we report the development and testing of a novel self-limiting gene drive system, Killer–Rescue (K–R), in Drosophila melanogaster. This system is composed of an autoregulated Gal4 Killer (K) and a Gal4-activated Gal80 Rescue (R). Overexpression of Gal4 is lethal, but in ... |
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Engineering multiple species-like genetic incompatibilities in insectsM. Maselko, N. Feltman, A. Upadhyay, A. Hayward, S. Das, N. Myslicki, A. J. Peterson, M. B. O’Connor and M. J. Smanski, bioRxiv, 2020.
Speciation constrains the flow of genetic information between populations of sexually reproducing organisms. Gaining control over mechanisms of speciation would enable new strategies to manage wild populations of disease vectors, agricultural pests, and invasive species. ... |
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Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elementsG. Oberhofer, T. Ivy and B. A. Hay, Proceedings of the National Academy of Sciences, 117:9013-9021. 2020.
Gene drive can spread beneficial traits through populations, but will never be a one-shot project in which one genetic element provides all desired modifications, for an indefinitely long time. Here, we show that gene drive-mediated population modification in Drosophila can be ... |
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Performance analysis of novel toxin-antidote CRISPR gene drive systemsJ. Champer, I. K. Kim, S. E. Champer, A. G. Clark and P. W. Messer, BMC Biology, 18:27. 2020.
CRISPR gene drive systems allow the rapid spread of a genetic construct throughout a population. Such systems promise novel strategies for the management of vector-borne diseases and invasive species by suppressing a target population or modifying it with a desired trait. ... |
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Dramatically diverse Schizosaccharomyces pombe wtf meiotic drivers all display high gamete-killing efficiencyM. A. Bravo Núñez, I. M. Sabbarini, M. T. Eickbush, Y. Liang, J. J. Lange, A. M. Kent and S. E. Zanders, PLOS Genetics, 16:e1008350. 2020.
During gametogenesis, the two gene copies at a given locus, known as alleles, are each transmitted to 50% of the gametes (e.g. sperm). However, some alleles cheat so that they are found in more than the expected 50% of gametes, often at the expense of fertility. This selfish ... |
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An introgressed gene causes meiotic drive in Neurospora sitophilaJ. Svedberg, A. A. Vogan, N. A. Rhoades, D. Sarmarajeewa, D. J. Jacobson, M. Lascoux, T. M. Hammond and H. Johannesson, bioRxiv, 2020.01.29.923946. 2020.
In this study, we identify the gene responsible for spore killing in Sk-1 by generating both long and short-read genomic data and by using these data to perform a genome wide association test. By phylogenetic analysis, we demonstrate that the gene is likely to have been ... |
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drivesChamper, 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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The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implicationsBeckmann, J. F., M. Bonneau, H. Chen, M. Hochstrasser, D. Poinsot, H. Merçot, M. Weill, M. Sicard and S. Charlat, Trends in Genetics, 35:175-185. 2019.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of ... |
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Gene drive and resilience through renewal with next generation Cleave and Rescue selfish genetic elementsOberhofer, G., T. Ivy and B. A. Hay, bioRxiv, 2019:2019.2012.2013.876169. 2019.
Gene drive-based strategies for modifying populations face the problem that genes encoding cargo and the drive mechanism are subject to separation, mutational inactivation, and loss of efficacy. Resilience, an ability to respond to these eventualities in ways that restore ... |
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Genetic Control of MosquitoesAlphey, L., Annual Review of Entomology, 59:205-224. 2019.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ... |
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The impact of local population genetic background on the spread of the selfish element Medea-1 in red flour beetlesS. A. Cash, M. A. Robert, M. D. Lorenzen and F. Gould, Ecology and Evolution, 12:1-12. 2019.
Selfish genetic elements have been found in the genomes of many species, yet our understanding of their evolutionary dynamics is only partially understood. A number of distinct selfish Medea elements are naturally present in many populations of the red flour beetle (Tribolium ... |
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The distribution and spread of naturally occurring Medea selfish genetic elements in the United StatesS. A. Cash, M. D. Lorenzen and F. Gould, Ecology and Evolution, 9:14407–14416.. 2019.
Selfish genetic elements (SGEs) are DNA sequences that are transmitted to viable offspring in greater than Mendelian frequencies. Medea SGEs occur naturally in some populations of red flour beetle (Tribolium castaneum) and are expected to increase in frequency within populations ... |
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Threshold-Dependent Gene Drives in the Wild: Spread, Controllability, and Ecological UncertaintyG. A. Backus and J. A. Delborne, BioScience, 69:900-907. 2019.
Gene drive technology could allow the intentional spread of a desired gene throughout an entire wild population in relatively few generations. However, there are major concerns that gene drives could either fail to spread or spread without restraint beyond the targeted ... |
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Identification of fk-1;, a Meiotic Driver Undergoing RNA Editing in NeurosporaN. A. Rhoades, A. M. Harvey, D. A. Samarajeewa, J. Svedberg, A. Yusifov, A. Abusharekh, P. Manitchotpisit, D. W. Brown, K. J. Sharp, D. G. Rehard, J. Peters, X. Ostolaza-Maldonado, J. Stephenson, P. K. T. Shiu, H. Johannesson and T. M. Hammond, Genetics, 212:93. 2019.
These findings indicate that unedited and edited rfk-1 transcripts exist and that these transcripts could have different roles with respect to the mechanism of meiotic drive by spore killing. Regardless of RNA editing, spore killing only succeeds if rfk-1 transcripts avoid ... |
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Cleave and Rescue, a novel selfish genetic element and general strategy for gene driveOberhofer, GI, T.; Hay, B. A., Proceedings of the National Academy of Sciences of the United States of America, 116:6250-6259. 2019.
There is great interest in being able to spread beneficial traits throughout wild populations in ways that are self-sustaining. Here, we describe a chromosomal selfish genetic element, CleaveR [Cleave and Rescue (ClvR)], able to achieve this goal. ClvR comprises two linked ... |
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Making a murderer: The evolutionary framing of hybrid gamete-killersSweigart, ALB, Yaniv; Fishman, Lila, Trends in Genetics, 35:245-252. 2019.
Recent molecular investigations of hybrid incompatibilities have revealed fascinating patterns of genetic interactions that have been interpreted as the remnants of a history of selfish evolution. Instead of framing hybrid incompatibilities in light of genetic conflict, we ... |
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The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implicationsBeckmann, JFB, Manon; Chen, Hongli; Hochstrasser, Mark; Poinsot, Denis; Merçot, Hervé; Weill, Mylène; Sicard, Mathieu; Charlat, Sylvain, Trends in Genetics, 35:175-185. 2019.
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of ... |
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Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in DrosophilaShropshire, JDB, S. R., PLOS Genetics, 15:e1008221. 2019.
Wolbachia are maternally inherited bacteria that infect arthropod species worldwide and are deployed in vector control to curb arboviral spread using cytoplasmic incompatibility (CI). CI kills embryos when an infected male mates with an uninfected female, but the lethality is ... |
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One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogasterShropshire, J. D., J. On, E. M. Layton, H. Zhou and S. R. Bordenstein, Proceedings of the National Academy of Sciences, 115:4987. 2018.
The World Health Organization recommended pilot deployment of Wolbachia-infected mosquitoes to curb viral transmission to humans. Releases of mosquitoes are underway worldwide because Wolbachia can block replication of these pathogenic viruses and deterministically spread by a ... |
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Gene drive to reduce malaria transmission in sub-Saharan AfricaBurt, AC, Mamadou; Crisanti, Andrea; Diabate, Abdoulaye; Kayondo, Jonathan K., Journal of Responsible Innovation, 5:S66-S80. 2018.
Despite impressive progress, malaria continues to impose a substantial burden of mortality and morbidity, particularly in sub-Saharan Africa, and new tools will be needed to achieve elimination. Gene drive is a natural process by which some genes are inherited at a ... |
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Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukiiBuchman, AM, John M.; Ostrovski, Dennis; Yang, Ting; Akbari, Omar S., Proceedings of the National Academy of Sciences of the United States of America, 115:4725-4730. 2018.
Here we describe a fully functional gene drive system constructed in a major worldwide crop pest, Drosophila suzukii. This system is composed of a synthetic Medea drive with a maternal miRNA “toxin” and a zygotic “antidote,” and we demonstrate that it can bias inheritance ... |
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Evolutionary genetics of cytoplasmic incompatibility genes cifA and cifB in prophage WO of WolbachiaLindsey, A. R. I., D. W. Rice, S. R. Bordenstein, A. W. Brooks, S. R. Bordenstein and I. L. G. Newton, Genome Biology and Evolution, 10:434-451. 2018.
The bacterial endosymbiont Wolbachia manipulates arthropod reproduction to facilitate its maternal spread through host populations. The most common manipulation is cytoplasmic incompatibility (CI): Wolbachia-infected males produce modified sperm that cause embryonic mortality, ... |
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Genetic villains: Killer meiotic driversBravo Núñez, MAN, Nicole L.; Zanders, Sarah E., Trends in Genetics, 34:424-433. 2018.
Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of ... |
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Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectorsEdgington, MPA, Luke S., PLOS Computational Biology, 14:e1006059. 2018.
Vector-borne diseases represent a severe burden to both human and animal health worldwide. The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand. As such, alternate methods for the control of vector-borne ... |
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Recent advances in threshold-dependent gene drives for mosquitoesLeftwich, PTE, Matthew P.; Harvey-Samuel, Tim; Carabajal Paladino, Leonela Z.; Norman, Victoria C.; Alphey, Luke, Biochemical Society Transactions, 46:1203-1212. 2018.
Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole ... |
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Gene drive: Evolved and syntheticBurt, AC, Andrea, ACS Chemical Biology, 13:343-346. 2018.
Drive is a process of accelerated inheritance from one generation to the next that allows some genes to spread rapidly through populations even if they do not contribute to—or indeed even if they detract from—organismal survival and reproduction. Genetic elements that can ... |
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A maternal-effect selfish genetic element in Caenorhabditis elegansE. Ben-David, A. Burga and L. Kruglyak, Science, 356:1051. 2017.
We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode Caenorhabditis elegans. |
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Poisons, antidotes, and selfish genesN. Phadnis, Science, 356:1013. 2017.
On page1051 of this issue, BenDavid et al . (3) chase down a serendipitous observation of an anomaly in genetic crosses to unmask a toxin-antidote type of selfish system in worms. |
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A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibilityBeckmann, J. F., J. A. Ronau and M. Hochstrasser, Nature Microbiology, 2:17007. 2017.
Wolbachia are obligate intracellular bacteria1 that infect arthropods, including approximately two-thirds of insect species2. Wolbachia manipulate insect reproduction by enhancing their inheritance through the female germline. The most common alteration is cytoplasmic ... |
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wtf genes are prolific dual poison-antidote meiotic driversNuckolls, NLN, M. A. B.; Eickbush, M. T.; Young, J. M.; Lange, J. J.; Yu, J. S.; Smith, G. R.; Jaspersen, S. L.; Malik, H. S.; Zanders, S. E., eLife, 6:e26033. 2017.
Meiotic drivers are selfish genes that bias their transmission into gametes, defying Mendelian inheritance. Despite the significant impact of these genomic parasites on evolution and infertility, few meiotic drive loci have been identified or mechanistically characterized. Here, ... |
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A large gene family in fission yeast encodes spore killers that subvert Mendel’s lawHu, WJ, Z. D.; Suo, F.; Zheng, J. X.; He, W. Z.; Du, L. L., eLife, 6:e28567. 2017.
Spore killers in fungi are selfish genetic elements that distort Mendelian segregation in their favor. It remains unclear how many species harbor them and how diverse their mechanisms are. Here, we discover two spore killers from a natural isolate of the fission yeast ... |
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Occasional recombination of a selfish X-chromosome may permit its persistence at high frequencies in the wildPieper, KED, K. A., Journal of Evolutionary Biology, 29:2229-2241. 2016.
The sex-ratio X-chromosome (SR) is a selfish chromosome that promotes its own transmission to the next generation by destroying Y-bearing sperm in the testes of carrier males. In some natural populations of the fly Drosophila neotestacea, up to 30% of the X-chromosomes are SR ... |
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Genetic Control of Mosquitoes.Alphey, L., Annual Review of Entomology, 59:205-224. 2014.
Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their ... |
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Dynamics of a combined medea-underdominant population transformation systemGokhale, 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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A selfish gene chastened: Tribolium castaneum Medea M (4) is silenced by a complementary geneThomson, MS, Genetica, 142:161-167. 2014.
Maternal-effect dominant embryonic arrest (Medea) of Tribolium castaneum are autosomal factors that act maternally to cause the death of any progeny that do not inherit them. This selfish behavior is thought to result from a maternally expressed poison and zygotically expressed ... |
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An X-linked sex ratio distorter in Drosophila simulans that kills or incapacitates both noncarrier sperm and sonsRice, WR, G3-Genes Genomes Genetics, 4:1837-1848. 2014.
Genomic conflict occurs when a genomic component gains a reproductive advantage at the expense of the organism as a whole. X-linked segregation distorters kill or incapacitate Y-bearing sperm, thereby gaining a transmission advantage but also reducing male fertility and ... |
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Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila: A theoretical exploration of Medea-dependent population suppressionAkbari, OSC, C. H.; Marshall, J. M.; Huang, H. X.; Antoshechkin, I.; Hay, B. A., ACS Synthetic Biology, 3:915-928. 2014.
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a ... |
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Medusa: A novel gene drive system for confined suppression of insect populationsMarshall, JMH, B. A., PLOS One, 9:e102694. 2014.
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 ... |
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Confinement of gene drive systems to local populations: A comparative analysisMarshall, 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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General principles of single-construct chromosomal gene driveMarshall, JMH, B. A., Evolution, 66:2150-2166. 2012.
Gene drive systems are genetic elements capable of spreading into a population even if they confer a fitness cost to their host. We consider a class of drive systems consisting of a chromosomally located, linked cluster of genes, the presence of which renders specific classes of ... |
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A novel sperm-delivered toxin causes late-stage embryo lethality and transmission ratio distortion in C. elegansSeidel, HSA, M.; Li, J. L.; van Oudenaarden, A.; Rockman, M. V.; Kruglyak, L., PLOS Biology, 9:e1001115. 2011.
The evolutionary fate of an allele ordinarily depends on its contribution to host fitness. Occasionally, however, genetic elements arise that are able to gain a transmission advantage while simultaneously imposing a fitness cost on their hosts. We previously discovered one such ... |
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Semele: A Killer-male, rescue-female system for suppression and replacement of insect disease vector populationsMarshall, JMP, G. W.; Buchman, A. B.; Hay, B. A., Genetics, 187:535-551. 2011.
Two strategies to control mosquito-borne diseases, such as malaria and dengue fever, are reducing mosquito population sizes or replacing populations with disease-refractory varieties. We propose a genetic system, Semele, which may be used for both. Semele consists of two ... |
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Gene-drive in age-structured insect populationsHuang, YXL, A. L.; Legros, M.; Gould, F., Evolutionary Applications, 2:143-159. 2009.
To date, models of gene-drive mechanisms proposed for replacing wild-type mosquitoes with transgenic strains that cannot transmit diseases have assumed no age or mating structure. We developed a more detailed model to analyze the effects of age and mating-related factors on the ... |
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A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructsGould, 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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Neurospora spore killers Sk-2 and Sk-3 suppress meiotic silencing by unpaired DNARaju, NBM, R. L.; Shiu, P. T., Genetics, 176:43-52. 2007.
In Neurosphora, crassa., pairing of homologous DNA segments is monitored during meiotic prophase I. Any genes not paired with a homolog, as well as any paired homologs of that gene, are silenced during the sexual phase by a mechanism known as meiotic silencing by unpaired DNA ... |
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Introducing transgenes into insect populations using combined gene-drive strategies: Modeling and analysisHuang, YXM, K.; Lloyd, A. L.; Gould, F., Insect Biochemistry and Molecular Biology, 37:1054-1063. 2007.
Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of ... |
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Spore-killing meiotic drive factors in a natural population of the fungus Podospora anserinavan der Gaag, MD, A. J. M.; Oosterhof, J.; Slakhorst, M.; Thijssen, Jagm; Hoekstra, R. F., Genetics, 156:593-605. 2000.
In fungi, meiotic drive is observed as spore killing. In the secondarily homothallic ascomycete Podospora anserina it is characterized by the abortion of two of the four spores in the ascus. We have identified seven different types of meiotic drive elements (Spore killers). Among ... |
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Meiotic drive in fungi: Chromosomal elements that cause fratricide and distort genetic ratiosRaju, NB, Journal of Genetics, 75:287-296. 1996.
Fungal Spore killers (Sk), studied most extensively in Neurospora and to a lesser extent in Podospora, Gibberella and Cochliobolus, cause the death of ascospores (= meiospores) that do not contain the killer (Sk(K)) element. When a Spore killer is heterozygous (Sk(K) x Sk(S)) in ... |
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Ascoycete spore killers: Chromosomal elements that distort genetic ratios among the products of meiosisRaju, NB, Mycologia, 86:461-473. 1994.
Spore killers (Sk), studied most extensively in Neurospora, are also known in Podospora, Gibberella and Cochliobolus. Spore killers are no doubt present in natural populations of other fungi. Criteria are outlined here for recognizing their presence and distinguishing them from ... |
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Hypothetical sisterkillerButcher, DLD, H. W., Nature, 369:26-26. 1994.
It was premature of Hurst in his News and Views article I to accept Haig's claim2 that a hypothetical meiotic drive element, SisterKiller, can lead to evolution from one-step to multi-step meiosis. The basis of Haig's claim is that a SisterKiller allele that causes a gamete to ... |
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Expression of meiotic drive elements Spore Killer-2 and Spore Killer-3 in asci of Neurospora tetraspermaRaju, NBP, D. D., Genetics, 129:25-37. 1991.
It was shown previously that when a chromosomal Spore killer factor is heterozygous in Neurospora species with eight-spored asci, the four sensitive ascospores in each ascus die and the four survivors are all killers. Sk-2K and Sk-3K are nonrecombining haplotypes that segregate ... |
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Genetics-driving genes and chromosomesCharlesworth, B, Nature, 332:394-395. 1988.
Thereare several genetic and chromosomal systems in which Mendel's first law - the equal probability of transmission of maternal and paternal alternative alleles or homologues - is violated. This phenomenon was named 'meiotic drive' in 1957 by Sandler and Novitski, who drew ... |
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Inheritance in Nicotiana tabacum XXVII. Pollen Killer, An alien genetic locus inducing abortion of microspores not carrying itD. R. Cameron and R. M. Moav, Genetics, 42:326. 1957.
A cytogenetic study of experimental introgression from N. plumbaginifolia (pbg) into N. tabacum (tbc) has been pursued in this laboratory for several years (CLAUSEN 1952). In the hybrid derivatives it was observed that genically controlled pollen abortion was associated with the ... |
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Studies of the genetic variability in populations of wild house mice .2. Analysis of eight additional alleles at locus – TL. C. Dunn, Genetics, 42:299-311. 1957.1 Eight additional lethal alleles at locus T are described, each derived from a wild heterozygote in one of six different wild populations. 2. The frequency of heterozygotes appears to be high in most wild populations, possibly as high as 50 percent. 3. In two of the ... |
