Keywords: gene drive mechanisms

A fly model establishes distinct mechanisms for synthetic CRISPR/Cas9 sex distorters

B. Fasulo, A. Meccariello, M. Morgan, C. Borufka, P. A. Papathanos and N. Windbichler,  PLOS Genetics,  16:e1008647. 2020.
Author summary Harmful insect populations can be eliminated for a lack of females if they are made to produce mostly male offspring. There are genes that occur naturally that make males produce mostly sons and, although we don’t know exactly how they work, this appears to ...
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Design and analysis of CRISPR-based underdominance toxin-antidote gene drives

Champer, J., S. E. Champer, I. Kim, A. G. Clark and P. W. Messer,  bioRxiv,  861435:861435. 2019.
CRISPR gene drive systems offer a mechanism for transmitting a desirable transgene throughout a population for purposes ranging from vector-borne disease control to invasive species suppression. In this simulation study, we model and assess the performance of several CRISPR-based ...
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The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications

Beckmann, 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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A novel drug-inducible sex separation technique for insects

Kandul, N. P., J. Liu, A. D. Hsu, B. A. Hay and O. S. Akbari,  bioRxiv,  2019:2019.12.13.875716. 2019.
Large sterile male releases are the gold standard for most insect population control methods and thus precise sex sorting is essential to the success of these technologies. Sex sorting is especially important for mosquito control because female mosquitoes bite and transmit ...
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A bacterial gene-drive system efficiently edits and inactivates a high copy number antibiotic resistance locus

Valderrama, J. A., S. S. Kulkarni, V. Nizet and E. Bier,  Nature Communications,  10:5726. 2019.
Gene-drive systems in diploid organisms bias the inheritance of one allele over another. CRISPR-based gene-drive expresses a guide RNA (gRNA) into the genome at the site where the gRNA directs Cas9-mediated cleavage. In the presence of Cas9, the gRNA cassette and any linked cargo ...
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New CRISPR system efficiently battles antibiotic resistance

Black, Samantha,  The Science Advisory Board,  2019.
Researchers from the University of California San Diego have developed a brand new CRISPR-based gene-drive system that dramatically increases the efficiency of inactivation of genes responsible for antibiotic resistance. The new system is detailed on December 16 in Nature ...
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Meiotic drive mechanisms: lessons from Drosophila

C. Courret, C.-H. Chang, K. H.-C. Wei, C. Montchamp-Moreau and A. M. Larracuente,  Proceedings of the Royal Society B: Biological Sciences,  286:20191430. 2019.
Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of ...
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Evolutionary simulations of Z-linked suppression gene drives

L. Holman,  Proceedings of the Royal Society B-Biological Sciences,  286:1-9. 2019.
Synthetic gene drives may soon be used to suppress or eliminate populations of disease vectors, pathogens, invasive species, and agricultural pests. Recent proposals have focused on using Z-linked gene drives to control species with ZW sex determination, which include ...
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Viral gene drive in herpesviruses

Walter, M. and E. Verdin,  bioRxiv,  2019:717017. 2019.
Herpesviruses are ubiquitous pathogens in need of novel therapeutic solutions. Current engineered gene drive strategies rely on sexual reproduction, and are thought to be restricted to sexual organisms. Here, we report on the design of a novel gene drive system that allows the ...
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Effective strategies for safeguarding CRISPR gene-drive experiments

ScienceDaily,  ScienceDaily,  2019.
Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene-drive experiments in the lab, according to a new study.
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Transmission ratio distortion is frequent in Arabidopsis thaliana controlled crosses

Seymour, DKC, E.; Arioz, B. I.; Koenig, D.; Weigel, D.,  Heredity,  122:294-304. 2019.
The equal probability of transmission of alleles from either parent during sexual reproduction is a central tenet of genetics and evolutionary biology. Yet, there are many cases where this rule is violated. The preferential transmission of alleles or genotypes is termed ...
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CRISPR gene drive efficiency and resistance rate is highly heritable with no common genetic loci of large effect

Champer, JW, Z. X.; Luthra, A.; Reeves, R.; Chung, J.; Liu, C.; Lee, Y. L.; Liu, J. X.; Yang, E.; Messer, P. W.; Clark, A. G.,  Genetics,  212:333-341. 2019.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. Clustered regularly interspaced short palindromic repeat (CRISPR) homing gene drives work by cleaving ...
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Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs

Buchman, AG, S.; Li, M.; Antoshechkin, I.; Li, H. H.; Wang, H. W.; Chen, C. H.; Klein, M. J.; Duchemin, J. B.; Paradkar, P. N.; Akbari, O. S.,  Proceedings of the National Academy of Sciences of the United States of America,  116:3656-3661. 2019.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or ...
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Super-Mendelian inheritance mediated by CRISPR-Cas9 in the female mouse germline

Grunwald, HAG, V. M.; Poplawski, G.; Xu, X. R. S.; Bier, E.; Cooper, K. L.,  Nature,  566:105-109. 2019.
A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of ...
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Gene drives in plants: opportunities and challenges for weed control and engineered resilience

Barrett, LGL, Mathieu; Kumaran, Nagalingam; Glassop, Donna; Raghu, S.; Gardiner, Donald M.,  Proceedings of the Royal Society B: Biological Sciences,  286:9. 2019.
Plant species, populations and communities are under threat from climate change, invasive pathogens, weeds and habitat fragmentation. Despite considerable research effort invested in genome engineering for crop improvement, the development of genetic tools for the management of ...
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Two-By-One model of cytoplasmic incompatibility: Synthetic recapitulation by transgenic expression of cifA and cifB in Drosophila

Shropshire, 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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Multiple loci of small effect confer wide variability in efficiency and resistance rate of CRISPR gene drive

J. Champer, Z. Wen, A. Luthra, R. Reeves, J. Chung, C. Liu, Y. L. Lee, J. Liu, E. Yang, P. W. Messer and A. G. Clark,  bioRxiv,  447615. 2018.
Gene drives could allow for control of vector-borne diseases by directly suppressing vector populations or spreading genetic payloads designed to reduce pathogen transmission. CRISPR homing gene drives work by cleaving wild-type alleles, which are then converted to drive alleles ...
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Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii

Buchman, 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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Genetic villains: Killer meiotic drivers

Bravo 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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Gene drive inhibition by the anti-CRISPR proteins AcrIIA2 and AcrIIA4 in Saccharomyces cerevisiae

Basgall, EMG, S. C.; Goeckel, M. E.; Giersch, R. M.; Roggenkamp, E.; Schrock, M. N.; Halloran, M.; Finnigan, G. C.,  Microbiology-Sgm,  164:464-474. 2018.
Given the widespread use and application of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas gene editing system across many fields, a major focus has been the development, engineering and discovery of molecular means to precisely control and regulate ...
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Improved CRISPR-based suppression gene drives mitigate resistance and impose a large reproductive load on laboratory-contained mosquito populations

Hammond, AMK, Kyros; Gribble, Matthew; Karlsson, Xenia; Morianou, Ioanna; Galizi, Roberto; Beaghton, Andrea; Crisanti, Andrea; Nolan, Tony,  bioRxiv,  360339:1-16. 2018.
CRISPR-based genes drives bias their own inheritance and can be used to modify entire populations of insect vectors of disease as a novel form of sustainable disease control. Gene drives designed to interfere with female fertility can suppress populations of the mosquito vector ...
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Kinetic basis for DNA target specificity of CRISPR-Cas12a

Strohkendl, IS, Fatema A.; Rybarski, James R.; Finkelstein, Ilya J.; Russell, Rick,  Molecular Cell,  71:816-824. 2018.
Summary Class 2 CRISPR-Cas nucleases are programmable genome editing tools with promising applications in human health and disease. However, DNA cleavage at off-target sites that resemble the target sequence is a pervasive problem that remains poorly understood mechanistically. ...
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Gene flow mediates the role of sex chromosome meiotic drive during complex speciation

Meiklejohn, CDL, Emily L.; Gordon, Kathleen E.; Rzatkiewicz, Thomas; Kingan, Sarah B.; Geneva, Anthony J.; Vedanayagam, Jeffrey P.; Muirhead, Christina A.; Garrigan, Daniel; Stern, David L.; Presgraves, Daven C.,  eLife,  7:e35468. 2018.
During speciation, sex chromosomes often accumulate interspecific genetic incompatibilities faster than the rest of the genome. The drive theory posits that sex chromosomes are susceptible to recurrent bouts of meiotic drive and suppression, causing the evolutionary build-up of ...
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Unexpected patterns of segregation distortion at a selfish supergene in the fire ant Solenopsis invicta

Ross, KGS, DeWayne,  BMC Genetics,  19:101. 2018.
The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this ...
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Veni, vidi, vici: the success of wtf meiotic drivers in fission yeast

López Hernández, JFZ, Sarah E.,  Yeast,  35:447-453. 2018.
Meiotic drivers are selfish DNA loci that can bias their own transmission into gametes. Owing to their transmission advantages, meiotic drivers can spread in populations even if the drivers or linked variants decrease organismal fitness. Meiotic drive was first formally described ...
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Development of a multi-locus CRISPR gene drive system in budding yeast

Yan, YF, Gregory C.,  Scientific reports,  8:17277-17277. 2018.
The discovery of CRISPR/Cas gene editing has allowed for major advances in many biomedical disciplines and basic research. One arrangement of this biotechnology, a nuclease-based gene drive, can rapidly deliver a genetic element through a given population and studies in fungi and ...
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Recent advances in threshold-dependent gene drives for mosquitoes

Leftwich, 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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Reducing resistance allele formation in CRISPR gene drive

Champer, JL, Jingxian; Oh, Suh Yeon; Reeves, Riona; Luthra, Anisha; Oakes, Nathan; Clark, Andrew G.; Messer, Philipp W.,  Proceedings of the National Academy of Sciences of the United States of America,  115:5522-5527. 2018.
A functioning gene drive mechanism could fundamentally change our strategies for the control of vector-borne diseases, such as malaria, dengue, and Zika. CRISPR homing gene drive promises such a mechanism, which could be used to rapidly spread genetic modifications among the ...
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A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes

Kyrou, KH, Andrew M.; Galizi, Roberto; Kranjc, Nace; Burt, Austin; Beaghton, Andrea K.; Nolan, Tony; Crisanti, Andrea,  Nature Biotechnology,  36:1062–1066. 2018.
In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) ...
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Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs

Oberhofer, GI, Tobin; Hay, Bruce A.,  Proceedings of the National Academy of Sciences of the United States of America,  115:e9343. 2018.
Homing endonuclease gene (HEG)-based gene drive can bring about population suppression when genes required for viability or fertility are targeted. However, these strategies are vulnerable to failure through mechanisms that create alleles resistant to cleavage but that retain ...
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Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management

Carrami, Eli M., ME, Kolja N.; Ahmed, Hassan M. M.; Sánchez C., Héctor M.; Dippel, Stefan; Marshall, John M.; Wimmer, Ernst A.,  Proceedings of the National Academy of Sciences of the United States of America,  115:6189-6194. 2018.
Resistance evolution caused by CRISPR/Cas9 gene-drive systems has a major impact on both the future scientific design of such gene-drive systems and on the politics of regulating experimentation and use of such systems. In our study, we show that in-frame drive-resistant alleles ...
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Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly

Verspoor Rudi, LSJ, M. L.; Mannion Natasha, L. M.; Hurst Gregory, D. D.; Price Tom, A. R.,  Evolution Letters,  2:169-179. 2018.
Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics ...
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Transmission and drive involving parasitic B chromosomes

Jones, RN,  Genes,  9:e388. 2018.
B chromosomes (Bs) are enigmatic additional elements in the genomes of thousands of species of plants, animals, and fungi. How do these non-essential, harmful, and parasitic chromosomes maintain their presence in their hosts, making demands on all the essential functions of their ...
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A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility

Beckmann, 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 drivers

Nuckolls, 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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Genetic conflicts: the usual suspects and beyond

McLaughlin, RNM, H. S.,  Journal of Experimental Biology,  220:6-17. 2017.
Selfishness is pervasive and manifests at all scales of biology, from societies, to individuals, to genetic elements within a genome. The relentless struggle to seek evolutionary advantages drives perpetual cycles of adaptation and counter-adaptation, commonly referred to as Red ...
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B chromosome in Plantago lagopus Linnaeus, 1753 shows preferential transmission and accumulation through unusual processes

Dhar, MKK, G.; Kaul, S.,  Comparative Cytogenetics,  11:375-391. 2017.
Plantago lagopus is a diploid (2n = 2x = 12) weed belonging to family Plantaginaceae. We reported a novel B chromosome in this species composed of 5S and 45S ribosomal DNA and other repetitive elements. In the present work, presence of B chromosome(s) was confirmed through FISH ...
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A pooled sequencing approach identifies a candidate meiotic driver in Drosophila

Wei, KHCR, H. M.; Rathnam, C.; Lee, J.; Lin, D. A. N.; Ji, S. Q.; Mason, J. M.; Clark, A. G.; Barbash, D. A.,  Genetics,  206:451-465. 2017.
Meiotic drive occurs when a selfish element increases its transmission frequency above the Mendelian ratio by hijacking the asymmetric divisions of female meiosis. Meiotic drive causes genomic conflict and potentially has a major impact on genome evolution, but only a few drive ...
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A large gene family in fission yeast encodes spore killers that subvert Mendel’s law

Hu, 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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B Chromosomes – A matter of chromosome drive

Houben, A,  Frontiers in Plant Science,  8:210. 2017.
B chromosomes are supernumerary chromosomes which are often preferentially inherited, deviating from usual Mendelian segregation. The balance between the so-called chromosome drive and the negative effects that the presence of Bs applies on the fitness of their host determines ...
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Driving out malaria

Nolan, TC, A.,  Scientist,  2017.
In recent years, researchers have sequenced the genomes of several Anopheles mosquito species, including those responsible for nearly all of the malaria transmission in Africa. With this information, they have begun to identify the genes underlying the insects’ ability to ...
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Prospects and challenges of CRISPR/Cas genome editing for the study and control of neglected vector-borne nematode diseases

M. Zamanian and E. C. Andersen,  The FEBS Journal,  283:3204-3221. 2016.