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.
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Alternative Techniques and Options for Risk Reduction of Gene Drives
11265Bernd Giese, Arnim von Gleich and Johannes L. Frieß, Gene Drives at Tipping Points, 2020-04-28 18:59:49.
In this chapter, we analyse and compare different types of gene drives as well as promising alternative approaches that may provide a reduced risk.
Limits of Knowledge and Tipping Points in the Risk Assessment of Gene Drive Organisms
11263Arnim von Gleich and Winfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:50:47.
New challengesTipping point in the risk assessment of genetically engineered (GE) organisms are expected to emerge in the context of so-called ‘gene drives’. Based on a review of findings from current knowledge of GE organisms, it is concluded that the risk assessment of gene drive organisms intended for release into the environment will inevitably suffer from major uncertainties, ‘unknowns’ and methodological problems: subsequent generations of GE organisms might show effects that were not observed or intended in the first generation. Unintended effects can, for example, emerge from interaction with genetic backgrounds within natural populations or be triggered by changing environmental conditions. Due to the increasing spatio-temporal complexity associated with the long-term persistence and propagation of GE organisms, risk assessment can no longer be expected to produce sufficiently reliable results. It has to be assumed that at a certain point in the dissolution of spatio-temporal boundariesa tipping point will be reached, that will make reliable risk assessment impossible. Moreover, methodological problems need to be overcome: the comparative approach that is the starting point for current European Food Safety Authority (EFSA)European Food Safety Authority (EFSA)’s environmental risk assessment might not be applicable due to the lack of suitable ‘comparators’. Despite increasing uncertainties, riskassessors and risk managers need to solve the problems of how to come to robust conclusions and make reliable decisions that take the precautionary principle(PP) into sufficient consideration. The introduction of a new step in the risk assessment of genetically engineered organisms has been suggested to solve these problems—which is the ‘spatio-temporal controllability’ and takes three criteria into account:(1)the biology of the target organisms,(2)their naturally occurring interactions with the environment (biotic and abiotic),(3)the intended biological characteristics (traitsTraits) of the GE organismsGenetically engineered organism.
Steps Towards a Precautionary Risk Governance of SPAGE Technologies Including Gene-Drives
11261Arnim von Gleich, Gene Drives at Tipping Points, 2020-04-28 18:44:32.
In view of the rapid dynamics of genetic engineering development (in particular regarding the ‘new gene-technologies’ gene editing, self-propagating artificial genetic elements (SPAGESelf-Propagating Artificial Genetic Elements (SPAGE)) and synthetic biology), the question is being intensively discussed whether the currently practiced risk governance is sufficient to guarantee the desired high level of health, consumer and environmental safety. Especially the extreme spatial and temporal environmental exposure due to released SPAGEs is identified as a problem because it leads to an enormous expansion of ignorance about possible situations and interactions. Therefore it requires measures based on the precautionary principle. Workable ways to integrate the precautionary principle into environmental risk assessment and risk regulation are being developed.
Model Concepts for Gene Drive Dynamics
11259Johnannes L. Frieß, Merle Preu and Broder Breckling, Gene Drives at Tipping Points, 2020-04-28 18:40:56.
The GeneTip project works on the conception and design modeling of population dynamics influenced by gene drives. In this pursuit, multiple different approaches and concepts have been developed to on one hand, be able to cover a broad perspective on the topic but on the other hand to also focus on different key aspects. In the following we present seven concepts based on different modeling approaches. In these model concepts our model organism is the olive fruit fly (Bactrocera oleae), which is a major pest species in agricultural olive production.
Case Study 2: Oilseed Rape (Brassica napus L.)
11257Johnannes L. Frieß, Broder Breckling, Kathrin Pascher and Windfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:36:22.
SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) (Self-Propagating Artificial Genetic Element) technologies allow for a proliferation of genetic information on the populationPopulation level at a higher rate than usual Mendelian inheritanceMendelian inheritance. Currently projected developments of SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) mainly aim at a reduction or suppressionSuppression of animal populationsPopulation which are considered to be harmful or undesirable (Oye et al. 2014). However, the application of SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) is not limited to animals only. In principle, also plant populationsPopulation can be targeted (National Academies of Sciences 2016). The GeneTip case study on oilseed rape (Brassica napus) is intended to assess, which interactions play a role in a plant-specific context to address relevant ecological interactions that need to be fully explored in order to estimate potential risksRisk.
Case Study 1: Olive Fruit Fly (Bactrocera oleae)
11255Merle Preu, Johannes L. Frieß, Broder Breckling and Winfried Schröder, Gene Drives at Tipping Points, 2020-04-28 18:31:15.
The olive fruit fly Bactrocera oleae is a phytophagous insect associated to olive trees (Olea europaea, Oleaceae). Its larvae monophagously feed on olive fruits, the fly is therefore considered the most severe pest of olive cultivation causing tremendous economic losses. The olive fly therefore poses a good example of a potential target organism in a European context. This case study revealed that uncertainties exist with regard to the dispersal capacity of gene drive-bearing olive flies, as well as concerning the high gene flow between different populations and most importantly with regard to the population bottlenecks that regularly occur in winter. These would significantly increase or decrease genetic variability between subpopulations and thereby severely jeopardize the intended outcome of any SPAGE-application.
Vulnerability Analysis of Ecological Systems
11253Carina R. Lalyer, Arnim von gleich, Bernd Giese, Gene Drives at Tipping Points, 2020-04-28 18:28:04.
Vulnerability analysis can be seen as the counterpart to technology characterization. Technology characterisation scrutinises the intervening technology. Vulnerability analyses potentially affected systems. That may be socio-ecological, socio-technical, socio-economic or other systems. In this chapter ecological systems are in focus.
Gene Drives Touching Tipping Points
11251Brodee Breckling, Arnim von Gleich,, Gene Drives at Tipping Points, 2020-04-28 18:24:58.
Tipping points and tipping elements, phase transitions and similar critical phenomena are widely discussed in scientific as well as socio-economic contexts as components to understand unforeseen far reaching changes and critical transitions from one stage into another in complex systems caused by small perturbations or gradual changes. For the risk assessment of self-propagating artificial genetic elements in self-sustaining population wild populationsof animals or plants, it is crucial to understand, where tipping elements could become relevant, how they could be anticipated and to what extent surprises and unexpected effects might occur.
Technology Characterisation
11249Johannes L. Frieß, Bernd Giese, Arnim von Gleich, Gene Drives at Tipping Point, 2020-04-28 18:21:27.
In recent years, innovation in genetic engineering brought forth a number of technologies to manipulate the fate of entire wild typeWild type populations. These technologies rely on the dissemination of synthetic genetic elements within a population of sexually reproducing species via the germline and are identified as Self-Propagating Artificial Genetic Elements (SPAGESelf-Propagating Artificial Genetic Elements (SPAGE)). Some secure their dissemination passively so that only offspring carrying the SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) will survive or be fertile. Others overcome the limitations of the Mendelian inheritance pattern by a distortion of allelic segregation or a fragmentation of chromosomes, resulting in e.g. an altered sex ratio. Genetic elements may also promote their preferred inheritance by a molecular mechanism. If a SPAGESelf-Propagating Artificial Genetic Elements (SPAGE) overcomes the Mendelian pattern of inheritance and is thereby enabled to spread and distribute a novel traits throughout a population – even defying natural selection – it is called a gene drive. If organisms have a comparably short generation time, as e.g. insects, then already after a few months, a large part of the population could express a new property transmitted by the gene drive. In particular, very invasivegene drives may be able to impose properties on entire populations that otherwise could not spread.
Gene Drives at Tipping Points
11247Amin von Gleich and Winfried Schroder, Gene Drives at Tipping Points, 2020-04-28 18:14:49.
This open access book reports on a pilot project aiming at collecting information on the socio-ecological risks that could arise in the event of an uncontrolled spread of genetically engineered organisms into the environment. The researchers will, for instance, be taking a closer look at genetically engineered oilseed rape, genetically engineered olive flies as well as plants and animals with so-called gene drives. The book mainly adresses researchers.
The Enterprise: A massive transposon carrying Spokt meiotic drive genes
15127A. A. Vogan, S. L. Ament-Velásquez, E. Bastiaans, O. Wallerman, S. J. Saupe, A. Suh and H. Johannesson, bioRxiv, 2020.03.25.007153. 2020-04-28 16:03:56.
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. anserina, despite what is an otherwise highly conserved genome structure. We have determined that the reason for its varying positions is that the Spok block is not only capable of meiotic drive, but is also capable of transposition. More precisely, the Spok block represents a unique case where the Enterprise has captured the Spoks, thereby parasitizing a resident genomic parasite to become a genomic hyperparasite.
The yeast mating-type switching endonuclease HO is a domesticated member of an unorthodox homing genetic element family
11244A. Y. Coughlan, L. Lombardi, S. Braun-Galleani, A. A. R. Martos, V. Galeote, F. Bigey, S. Dequin, K. P. Byrne and K. H. Wolfe, eLife, 9:e55336. 2020-04-27 17:30:45.
The mating-type switching endonuclease HO plays a central role in the natural life cycle of Saccharomyces cerevisiae, but its evolutionary origin is unknown. HO is a recent addition to yeast genomes, present in only a few genera close to Saccharomyces. Here we show that HO is structurally and phylogenetically related to a family of unorthodox homing genetic elements found in Torulaspora and Lachancea yeasts. These WHO elements home into the aldolase gene FBA1, replacing its 3' end each time they integrate. They resemble inteins but they operate by a different mechanism that does not require protein splicing. We show that a WHO protein cleaves Torulaspora delbrueckii FBA1 efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps during WHO element homing are very similar to those during mating-type switching, and indicate that HO is a domesticated WHO-like element.
Mosquito-Borne Diseases Emergence/Resurgence and How to Effectively Control It Biologically
12383H. Dahmana and O. Mediannikov, Pathogens, 9:26. 2020-04-23 17:49:22.
Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance.
Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania
11461M. F. Finda, N. Christofides, J. Lezaun, B. Tarimo, P. Chaki, A. H. Kelly, N. Kapologwe, P. Kazyoba, B. Emidi and F. O. Okumu, Malaria Journal, 19:164. 2020-04-23 15:13:29.
Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania.
Development and testing of a novel killer–rescue self-limiting gene drive system in Drosophila melanogaster
11214S. H. Webster, M. R. Vella and M. J. Scott, Proceedings of the Royal Society B: Biological Sciences, 287:20192994. 2020-04-15 15:04:49.
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 the presence of R activation of Gal80 leads to much lower levels of Gal4 and rescue of lethality. We demonstrate that with a single 2 : 1 engineered to wild-type release, K drives R through the population and after nine generations, more than 98% of the population carry R and less than 2% of the population are wild-type flies. We discuss how this simple K–R gene drive system may be readily adapted for population replacement in a human health pest, Aedes aegypti, or for population suppression in an agricultural pest, Drosophila suzukii.
Selfish genes and sexual selection: the impact of genomic parasites on host reproduction
11970N. Wedell, Journal of Zoology, 311:1-12. 2020-04-08 18:18:42.
Selfish genetic elements (SGEs) such as replicating mobile elements, segregation distorters and maternally inherited endosymbionts, bias their transmission success relative to the rest of the genome to increase in representation in subsequent generations. As such, they generate conflict with the rest of the genome. Such intragenomic conflict is also a hallmark of sexually antagonistic (SA) alleles, which are shared genes between the sexes but that have opposing fitness effects when expressed in males and females. However, whilst both SGEs and SA alleles are recognized as common and potent sources of genomic conflict, the realization that SGEs can also generate sexually antagonistic selection and contribute to sexual conflict in addition to generate sexual selection is largely overlooked. Here, I show that SGEs frequently generate sex-specific selection and outline how SGEs that are associated with compromised male fertility can shape female mating patterns, play a key role in the dynamics of sex-determination systems and likely be an important source of sexually antagonistic genetic variation. Given the prevalence of SGEs, their contribution to sexual conflict is likely to be greatly overlooked.
Spatio-temporal controllability and environmental risk assessment of genetically engineered gene drive organisms from the perspective of EU GMO Regulation
11208C. Then, K. Kawall and N. Valenzuela, Integrated Environmental Assessment and Management, 2020-04-06 14:38:52.
Gene drive organisms are a recent development created by using methods of genetic engineering; they inherit genetic constructs that are passed on to future generations with a higher probability than with Mendelian inheritance. There are some specific challenges inherent to the environmental risk assessment (ERA) of genetically engineered (GE) gene drive organisms, since subsequent generations of these GE organisms might show effects that were not observed or intended in the former generations. Unintended effects can emerge from interaction of the gene drive construct with the heterogeneous genetic background of natural populations and/or be triggered by changing environmental conditions. This is especially relevant in case of gene drives with invasive characteristics and typically takes dozens of generations to render the desired effect. Under these circumstances, ‘next generation effects’ can substantially increase the spatial and temporal complexity associated with a high level of uncertainty in ERA. To deal with these problems, we suggest the introduction of a new additional step in the ERA of GE gene drive organisms that takes three criteria into account: the biology of the target organisms, their naturally occurring interactions with the environment (biotic and abiotic) and their intended biological characteristics introduced by genetic engineering. These three criteria are merged to form an additional step in ERA, combining specific ‘knowns’ and integrating areas of 'known unknowns' and uncertainties, with the aim of assessing the spatio‐temporal controllability of GE gene drive organisms. The establishment of assessing spatio‐temporal controllability can be used to define so‐called ‘cut‐off’ criteria in the risk analysis of GE gene drive organisms: if it is likely that GE gene drive organisms escape spatio‐temporal controllability, the risk assessment cannot be sufficiently reliable because it is not conclusive. Under such circumstances, the environmental release of the GE gene drive organisms would not be compatible with the precautionary principle (PP).
Natural gene drives offer potential pathogen control strategies in plants
11206D. M. Gardiner, A. Rusu, L. Barrett, G. C. Hunter and K. Kazan, bioRxiv, 2020-04-06 14:21:48.
Globally, fungal pathogens cause enormous crop losses and current control practices are not always effective, economical or environmentally sustainable. Tools enabling genetic management of wild pathogen populations could potentially solve many problems associated with plant diseases. A natural gene drive from a heterologous species can be used in the globally important cereal pathogen, Fusarium graminearum, to remove pathogenic traits from contained populations of the fungus. The gene drive element became fixed in a freely crossing populations in only three generations. Repeat induce point mutation, a natural genome defence mechanism in fungi, may be useful to recall the gene drive following release, should a failsafe mechanism be required. We propose that gene drive technology is a potential tool to control plant pathogens.
Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations
22639J. E. Crawford, D. W. Clarke, V. Criswell, M. Desnoyer, D. Cornel, B. Deegan, K. Gong, K. C. Hopkins, P. Howell, et al., Nature Biotechnology, 38:482-492. 2020-04-06 06:19:43.
The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6–96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs.
Engineering multiple species-like genetic incompatibilities in insects
12543M. Maselko, N. Feltman, A. Upadhyay, A. Hayward, S. Das, N. Myslicki, A. J. Peterson, M. B. O’Connor and M. J. Smanski, bioRxiv, 2020-04-05 17:32:23.
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. Additionally, such control would provide safe biocontainment of transgenes and gene drives. Natural speciation can be driven by pre-zygotic barriers that prevent fertilization or by post-zygotic genetic incompatibilities that render the hybrid progeny inviable or sterile. Here we demonstrate a general approach to create engineered genetic incompatibilities (EGIs) in the model insect Drosophila melanogaster. Our system couples a dominant lethal transgene with a recessive resistance allele. EGI strains that are homozygous for both elements are fertile and fecund when they mate with similarly engineered strains, but incompatible with wild-type strains that lack resistant alleles. We show that EGI genotypes can be tuned to cause hybrid lethality at different developmental life-stages. Further, we demonstrate that multiple orthogonal EGI strains of D. melanogaster can be engineered to be mutually incompatible with wild-type and with each other. Our approach to create EGI organisms is simple, robust, and functional in multiple sexually reproducing organisms.
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