Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
Disclaimer>

Evolutionary dynamics of CRISPR gene drives

4059
Noble, CO, Jason; Esvelt, Kevin M.; Church, George M.; Nowak, Martin A.,  Science Advances,  3:e1601964. 2017-01-17 00:00:00.
The alteration of wild populations has been discussed as a solution to a number of humanity’s most pressing ecological and public health concerns. Enabled by the recent revolution in genome editing, clustered regularly interspaced short palindromic repeats (CRISPR) gene drives—selfish genetic elements that can spread through populations even if they confer no advantage to their host organism—are rapidly emerging as the most promising approach. However, before real-world applications are considered, it is imperative to develop a clear understanding of the outcomes of drive release in nature. Toward this aim, we mathematically study the evolutionary dynamics of CRISPR gene drives. We demonstrate that the emergence of drive-resistant alleles presents a major challenge to previously reported constructs, and we show that an alternative design that selects against resistant alleles could greatly improve evolutionary stability. We discuss all results in the context of CRISPR technology and provide insights that inform the engineering of practical gene drive systems.%U

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

4039
Eckhoff, PAW, E. A.; Godfray, H. C. J.; Burt, A.,  Proceedings of the National Academy of Sciences of the United States of America,  114:e255-e264. 2017-01-17 00:00:00.
The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.

CRISPR/Cas9 gene drives in genetically variable and nonrandomly mating wild populations

4038
Drury, DWD, A. L.; Siniard, D. J.; Zentner, G. E.; Wade, M. J.,  Science Advances,  3:e1601910. 2017-01-16 00:00:00.
Synthetic gene drives based on CRISPR/Cas9 have the potential to control, alter, or suppress populations of crop pests and disease vectors, but it is unclear how they will function in wild populations. Using genetic data from four populations of the flour beetle Tribolium castaneum, we show that most populations harbor genetic variants in Cas9 target sites, some of which would render them immune to drive (ITD). We show that even a rare ITD allele can reduce or eliminate the efficacy of a CRISPR/Cas9-based synthetic gene drive. This effect is equivalent to and accentuated by mild inbreeding, which is a characteristic of many disease-vectoring arthropods. We conclude that designing such drives will require characterization of genetic variability and the mating system within and among targeted populations.

Genetic conflicts: the usual suspects and beyond

4058
McLaughlin, RNM, H. S.,  Journal of Experimental Biology,  220:6-17. 2017-01-16 00:00:00.
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 Queen interactions. In this review, we explore insights gleaned from molecular and genetic studies of such genetic conflicts, both extrinsic (between genomes) and intrinsic (within genomes or cells). We argue that many different characteristics of selfish genetic elements can be distilled into two types of advantages: an over-replication advantage (e.g. mobile genetic elements in genomes) and a transmission distortion advantage (e.g. meiotic drivers in populations). These two general categories may help classify disparate types of selfish genetic elements.

B chromosome in Plantago lagopus Linnaeus, 1753 shows preferential transmission and accumulation through unusual processes

4037
Dhar, MKK, G.; Kaul, S.,  Comparative Cytogenetics,  11:375-391. 2017-01-15 00:00:00.
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 on root tip and pollen mother cells. Several experiments were done to determine the transmission of B chromosome through male and female sex tracks. Progenies derived from the reciprocal crosses between plants with (1B) and without (0B) B chromosomes were studied. The frequency of B chromosome bearing plants was significantly higher than expected, in the progeny of 1B female x 0B male. Thus, the B chromosome seems to have preferential transmission through the female sex track, which may be due to meiotic drive. One of the most intriguing aspects of the present study was the recovery of plants having more chromosomes than the standard complement of 12 chromosomes. Such plants were isolated from the progenies of B chromosome carrying plants. The origin of these plants can be explained on the basis of a two step process; formation of unreduced gametes in 1B plants and fusion of unreduced gametes with the normal gametes or other unreduced gametes. Several molecular techniques were used which unequivocally confirmed similar genetic constitution of 1B (parent) and plants with higher number of chromosomes.

Engineering species-like barriers to sexual reproduction

4057
Maselko, MH, Stephen C.; Chacón, Jeremy M.; Harcombe, William R.; Smanski, Michael J.,  Nature Communications,  8:883. 2017-01-15 00:00:00.
Controlling the exchange of genetic information between sexually reproducing populations has applications in agriculture, eradication of disease vectors, control of invasive species, and the safe study of emerging biotechnology applications. Here we introduce an approach to engineer a genetic barrier to sexual reproduction between otherwise compatible populations. Programmable transcription factors drive lethal gene expression in hybrid offspring following undesired mating events. As a proof of concept, we target the ACT1 promoter of the model organism Saccharomyces cerevisiae using a dCas9-based transcriptional activator. Lethal overexpression of actin results from mating this engineered strain with a strain containing the wild-type ACT1 promoter.

Gene drives do not always increase in frequency: from genetic models to risk assessment

4036
de Jong, TJ,  Journal Fur Verbraucherschutz Und Lebensmittelsicherheit-Journal of Consumer Protection and Food Safety,  12:299-307. 2017-01-14 00:00:00.
Homing genes encode endonucleases that make a double stranded break in the DNA, destroying a target site on the homologous chromosome. When the cell repairs the break the homing allele is copied, converting a heterozygote into a homozygote. This results in gene drive (GD), an overrepresentation of the homing allele in the next generation. GD may propel CRISPR-Cas9 genes and new genes physically coupled to the GD through natural populations. I revisit the population genetic models of GD with the aim of making these models more understandable to non-specialists. What can we learn about risk evaluation from the models? A GD with no or a small effect on fitness (viability) always spreads in the population and goes to fixation. That is provided that no resistance mechanism evolves, for instance due to a mutation in the target site. However, when GDs have a large negative effect on fitness, their spread depends on a threshold or they may not spread at all. The chance of GDs increasing until fixation is much higher in systems with meiotic drive than in systems with embryo conversion. The presence or absence of a meiotic promoter is therefore relevant to take into account in the environmental risk assessment.

Sperm competition suppresses gene drive among experimentally evolving populations of house mice

4056
Manser, AL, A. K.; Simmons, L. W.; Firman, R. C.,  Molecular Ecology,  26:5784-5792. 2017-01-14 00:00:00.
Drive genes are genetic elements that manipulate the 50% ratio of Mendelian inheritance in their own favour, allowing them to rapidly propagate through populations. The action of drive genes is often hidden, making detection and identification inherently difficult. Yet drive genes can have profound evolutionary consequences for the populations that harbour them: most known drivers are detrimental to organismal gamete development, reproduction and survival. In this study, we identified the presence of a well-known drive gene called t haplotype post hoc in eight replicate selection lines of house mice that had been evolving under enforced monandry or polyandry for 20 generations. Previous work on these selection lines reported an increase in sperm competitive ability in males evolving under polyandry. Here, we show that this evolutionary response can be partly attributed to gene drive. We demonstrate that drive-carrying males are substantially compromised in their sperm competitive ability. As a consequence, we found that t frequencies declined significantly in the polyandrous lines while remaining at stable, high levels in the monandrous lines. For the first time in a vertebrate, we thus provide direct experimental evidence that the mating system of a species can have important repercussions on the spread of drive genes over evolutionary relevant timescales. Moreover, our work highlights how the covert action of drive genes can have major, potentially unintended impact on our study systems.

The promise and peril of CRISPR gene drives

4076
Zentner, GEW, Michael J. C.,  Bioessays,  39:1-9. 2017-01-14 00:00:00.
Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats (CRISPR) genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives.

A bigger toolbox: Biotechnology in biodiversity conservation

6012
R. T. Corlett,  Trends in Biotechnology,  35:55-65. 2017-01-13 20:08:47.
Conservation biology needs a bigger toolbox to meet unprecedented challenges. Genomics, fueled by declining sequencing costs, offers novel tools with increased precision for genetic questions previously answered with a few molecular markers, as well as completely new possibilities. Metabarcoding promises quicker, cheaper, and more accurate assessments of biodiversity in groups that are difficult to assess by traditional methods, while sequencing low-quality DNA extends the range of useable materials to include museum specimens, archeological remains, and environmental samples. Genomic and transcriptomic data can be used to assess the potential of populations to adapt to new challenges. In the near future, gene-editing tools may help endangered species cope with change, while gene drives control unwanted species and help wanted ones. De-extinction has become a serious prospect.

Agricultural pest control with CRISPR-based gene drive: time for public debate: Should we use gene drive for pest control?

4035
Courtier?Orgogozo, VM, Baptiste; Boëte, Christophe,  EMBO Reports,  18:878-880. 2017-01-13 00:00:00.
Gene drive based on the CRISPR/Cas-9 gene editing system is a powerful technology that promotes the inheritance of the gene drive tool itself via sexual reproduction and can therefore spread quickly through a population. It holds great potential for public health and humanitarian purposes, such as reducing the burden of vector-borne diseases like malaria. Here, we discuss another potential application of CRISPR-based gene drive, namely the control of pest species to increase crop production. We argue that gene drive-based pest control strategies should receive more attention from policymakers and the public given their enormous potential impact on the environment, their easy accessibility, and the current dearth of regulations.

Gene Drive for Mosquito Control: Where Did It Come from and Where Are We Headed?

4055
Macias, VMO, J. R.; Rasgon, J. L.,  International Journal of Environmental Research and Public Health,  14:e1006. 2017-01-13 00:00:00.
Mosquito-borne pathogens place an enormous burden on human health. The existing toolkit is insufficient to support ongoing vector-control efforts towards meeting disease elimination and eradication goals. The perspective that genetic approaches can potentially add a significant set of tools toward mosquito control is not new, but the recent improvements in site-specific gene editing with CRISPR/Cas9 systems have enhanced our ability to both study mosquito biology using reverse genetics and produce genetics-based tools. Cas9-mediated gene-editing is an efficient and adaptable platform for gene drive strategies, which have advantages over innundative release strategies for introgressing desirable suppression and pathogen-blocking genotypes into wild mosquito populations; until recently, an effective gene drive has been largely out of reach. Many considerations will inform the effective use of new genetic tools, including gene drives. Here we review the lengthy history of genetic advances in mosquito biology and discuss both the impact of efficient site-specific gene editing on vector biology and the resulting potential to deploy new genetic tools for the abatement of mosquito-borne disease.

Unintended consequences of 21st century technology for agricultural pest management

4075
Young, SL,  EMBO reports,  18:1478-1478. 2017-01-13 00:00:00.
Comment on Agricultural pest control with CRISPR-based gene drive: time for public debate by Courtier-Orgogozo et al.

Adaptive risk management of gene drive experiments: Biosafety, biosecurity, and ethics

4054
Lunshof, JEB, A.,  Applied Biosafety,  22:97-103. 2017-01-12 00:00:00.
Emerging technologies in the life sciences call for new models of biosafety risk management. We examine the question of how to; address new developments in the life sciences and biosciences in a bottom-up manner—that is, from the concrete level of; biosafety practice with a focus on the risk management and risk assessment of emerging technologies in the biology laboratory.; We use research on “gene drives” as an example of challenging work with new constructs that have major biosafety implications; for the work in the laboratory and beyond. Gene drives are intended for use in ecosystems and require, at an early stage, the; consideration of potential future biosafety, biosecurity, and societal impact. We argue for an integrative approach, a truly collaborative; model that involves scientists, biosafety officers, institutional leadership, and ethics consultants, with the aim of; maximizing safety as well as scientific progress.

Introduction of a male-harming mitochondrial haplotype via ‘Trojan Females’ achieves population suppression in fruit flies

4074
Wolff, JNG, N. J.; Tompkins, D. M.; Dowling, D. K.,  eLife,  6:e23551. 2017-01-12 00:00:00.
Pests are a global threat to biodiversity, ecosystem function, and human health. Pest control approaches are thus numerous, but their implementation costly, damaging to non-target species, and ineffective at low population densities. The Trojan Female Technique (TFT) is a prospective self-perpetuating control technique that is species-specific and predicted to be effective at low densities. The goal of the TFT is to harness naturally occurring mutations in the mitochondrial genome that impair male fertility while having no effect on females. Here, we provide proof-of-concept for the TFT, by showing that introduction of a male fertility-impairing mtDNA haplotype into replicated populations of Drosophila melanogaster causes numerical population suppression, with the magnitude of effect positively correlated with its frequency at trial inception. Further development of the TFT could lead to establishing a control strategy that overcomes limitations of conventional approaches, with broad applicability to invertebrate and vertebrate species, to control environmental and economic pests.

Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations

4034
Champer, JR, Riona; Oh, Suh Yeon; Liu, Chen; Liu, Jingxian; Clark, Andrew G.; Messer, Philipp W.,  PLOS Genetics,  13:e1006796. 2017-01-12 00:00:00.
Author summary Gene drive systems provide a wide array of potential applications, including new strategies for the control of vector-borne diseases. For example, a functioning gene drive system could rapidly spread a genetically modified allele designed to reduce pathogen transmission throughout a vector population. The recently developed CRISPR/Cas9-based gene drive mechanism works by converting wild type alleles to drive alleles in heterozygotes via cleavage and homology-directed repair. However, resistance alleles that are unable to be converted to drive alleles can also be generated during this process, which may pose a major obstacle to the practical use of such gene drives. In our study, we developed two CRISPR/Cas9 gene drive constructs using different promoters and target sites in the model organism Drosophila melanogaster. We observed that these constructs produced resistance alleles at high rates both in the germline and post-fertilization in the embryo. Additionally, conversion efficiency and resistance allele formation rates varied substantially among genetically diverse fly lines. Overall, we conclude that new gene drive approaches will be necessary to reduce the formation of resistance alleles, particularly in genetically diverse natural populations.

A transatlantic perspective on 20 emerging issues in biological engineering

4073
Wintle, BCB, C. R.; Rhodes, C.; Molloy, J. C.; Millett, P.; Adam, L.; Breitling, R.; Carlson, R.; Casagrande, R.; Dando, M.; Doubleday, R.; Drexler, E.; Edwards, B.; Ellis, T.; Evans, N. G.; Hammond, R.; Haseloff, J.; Kahl, L.; Kuiken, T.; Lichman, B. R.; Matthewman, C. A.; Napier, J. A.; OhEigeartaigh, S. S.; Patron, N. J.; Perello, E.; Shapira, P.; Tait, J.; Takano, E.; Sutherland, W. J.,  eLife,  6:21. 2017-01-11 00:00:00.
Advances in biological engineering are likely to have substantial impacts on global society. To explore these potential impacts we ran a horizon scanning exercise to capture a range of perspectives on the opportunities and risks presented by biological engineering. We first identified 70 potential issues, and then used an iterative process to prioritise 20 issues that we considered to be emerging, to have potential global impact, and to be relatively unknown outside the field of biological engineering. The issues identified may be of interest to researchers, businesses and policy makers in sectors such as health, energy, agriculture and the environment.

Gene Drive 101: A Basic Guidance Resource for Biosafety Professionals

4053
Krishnan, PG, David,  Applied Biosafety,  22:181-184. 2017-01-11 00:00:00.
Biosafety risk assessment and containment framework strategies for research involving gene drives pose a challenge, as there are no published guidelines or regulatory information yet written specifically addressing biosafety and gene drive use. Since the risk is more at an ecologic population level than an individual risk to the researcher, this further confounds the typical risk assessment process, which traditionally places emphasis on evaluating biosafety risks to the user and how the agent is spread among permissible hosts. We also realize that many of the publications currently available for gene drive biosafety are written with the assumption that readers have a good grasp of molecular biology and genetics. We have good reason to believe that this assumption is neither correct nor justified among all biosafety professionals. Our goal here is to create a resource that would offer a basic primer on gene drive technology while providing enough resources to start the risk assessment process of a gene drive proposal. We developed several questions and answers that we believe will make tackling the biosafety aspects of a gene proposal less formidable.

Teilhard de Chardin’s oeuvre within an ongoing discussion of a gene drive release for public health reasons

4033
Cartolovni, A,  Life Sciences, Society and Policy,  13:18. 2017-01-11 00:00:00.
Within the domain of public health, vector-borne diseases are among the most vehemently discussed issues. Recent scientific breakthroughs in genome editing technology provided a solution to this issue in the form of a gene drive that might decrease and even eradicate vector-borne diseases. Gene drives are engineered, and designed genes that can break typical inheritance rules and be passed to almost all of the carrier’s offspring. This genome editing and gene drive technology has become a powerful tool for ecological and environmental engineering, through which man can manipulate his surroundings, adjusting it to himself and directly mastering evolution and the ecosystem. Although the gene drive technology has been perceived as promising in the public health domain, ecological implications of its use are not to be underestimated. The primary aim of this paper is to overcome the ongoing discussion which mostly focuses on whether priority should be given to the environment or to public health, and to find an adequate answer and solution. In this quest to find the proper answer and solution, Pierre Teilhard de Chardin’s thought might be useful, especially his concepts of the biosphere and the noosphere which may provide some clarifications as to why we are at the moment so cautious with gene drive technology and how we need to move towards a better common future on earth.

A pooled sequencing approach identifies a candidate meiotic driver in Drosophila

4072
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. 2017-01-10 00:00:00.
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 loci of large effect have been described. New methods to reliably detect meiotic drive are therefore needed, particularly for discovering moderate-strength drivers that are likely to be more prevalent in natural populations than strong drivers. Here, we report an efficient method that uses sequencing of large pools of backcross (BC1) progeny to test for deviations from Mendelian segregation genome-wide with single-nucleotide polymorphisms (SNPs) that distinguish the parental strains. We show that meiotic drive can be detected by a characteristic pattern of decay in distortion of SNP frequencies, caused by recombination unlinking the driver from distal loci. We further show that control crosses allow allele-frequency distortion caused by meiotic drive to be distinguished from distortion resulting from developmental effects. We used this approach to test whether chromosomes with extreme telomere-length differences segregate at Mendelian ratios, as telomeric regions are a potential hotspot for meiotic drive due to their roles in meiotic segregation and multiple observations of high rates of telomere sequence evolution. Using four different pairings of long and short telomere strains, we find no evidence that extreme telomere-length variation causes meiotic drive in Drosophila. However, we identify one candidate meiotic driver in a centromere-linked region that shows an similar to 8% increase in transmission frequency, corresponding to a similar to 54: 46 segregation ratio. Our results show that candidate meiotic drivers of moderate strength can be readily detected and localized in pools of BC1 progeny.

« First ‹ Previous 1 79 87 88 89 90 91 99 118 Next › Last »