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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Biological control of pests and a social model of animal welfare

16284
A. Mankad, U. Kennedy and L. Carter,  Journal of Environmental Management,  247:313-322. 2019-06-25 17:21:12.
We consider the role of perceived humaneness or, more accurately, animal welfare as it relates to managing invasive species from a scientific and social perspective. In order to highlight and articulate particular nuances and standards across different pest control contexts, we use three case examples (feral cats, wild rabbits, and invasive cane toads) and explore where biological pest control and animal welfare interests intersect.

The association between mitochondrial genetic variation and reduced colony fitness in an invasive wasp

13731
J. Dobelmann, A. Alexander, J. W. Baty, N. J. Gemmell, M. A. M. Gruber, O. Quinn, T. Wenseleers and P. J. Lester,  Molecular Ecology,  28:3324-3338. 2019-06-24 19:25:29.
Despite the mitochondrion's long-recognized role in energy production, mitochondrial DNA (mtDNA) variation commonly found in natural populations was assumed to be effectively neutral. However, variation in mtDNA has now been increasingly linked to phenotypic variation in life history traits and fitness. We examined whether the relative fitness in native and invasive common wasp (Vespula vulgaris) populations in Belgium and New Zealand (NZ), respectively, can be linked to mtDNA variation.

A century of bias in genetics and evolution

6691
L. D. Hurst,  Heredity,  123:33-44. 2019-06-12 17:55:20.
Mendel proposed that the heritable material is particulate and that transmission of alleles is unbiased. An assumption of unbiased transmission was necessary to show how variation can be preserved in the absence of selection, so overturning an early objection to Darwinism. In the second half of the twentieth century, it was widely recognised that even strongly deleterious alleles can invade if they have strongly biased transmission (i.e. strong segregation distortion). The spread of alleles with distorted segregation can explain many curiosities. More recently, the selectionist-neutralist duopoly was broken by the realisation that biased gene conversion can explain phenomena such as mammalian isochore structures. An initial focus on unbiased transmission in 1919, has thus given way to an interest in biased transmission in 2019. A focus on very weak bias is now possible owing to technological advances, although technical biases may put a limit on resolving power. To understand the relevance of weak bias we could profit from having the concept of the effectively Mendelian allele, a companion to the effectively neutral allele. Understanding the implications of unbiased and biased transmission may, I suggest, be a good way to teach evolution so as to avoid psychological biases.

A synthetic male-specific sterilization system using the mammalian pro-apoptotic factor in a malaria vector mosquito

16645
D. S. Yamamoto, M. Sumitani, K. Kasashima, H. Sezutsu, H. Matsuoka and H. Kato,  Scientific Reports,  9:11. 2019-06-03 19:52:01.
We produced a transgenic mosquito line that expresses mouse Bax under the control of this testis-specific promoter. Transgenic mosquito males exhibited aberrant testes without functional sperm and complete sterility, whereas transgenic females maintained normal fecundity. Despite their abnormal testes, the transgenic males maintained normal function of male accessory glands and typical mating behaviour. As a result of mating with these males, females showed refractoriness to further mating. These results suggest that transgenic males induce female sterility via mating. The mosquito is one of the most important disease vectors, and the control of their population benefits global public health.

Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection on Islands: Workshop Report

11581
M. Farooque, S. K. Barnhill-Dilling, J. Shapiro and J. Delborne,  North Carolina State University,  2019-06-01 15:28:38.
The “Exploring Stakeholder Perspectives on the Development of a Gene Drive Mouse for Biodiversity Protection” workshop was held on the North Carolina State University campus in Raleigh, NC on March 7-8, 2019, aiming to convene a diverse group of stakeholders, scientists, funders, and leaders for an exploration of perspectives on the development of a gene drive mouse for restoring biodiversity on islands. Information collected at the workshop is presented in this report to inform upcoming decisions by the NCSU-Safe Genes research team about research, testing, and potential deployment of technologies (the Safe Genes program does not fund any environmental releases of gene drive modified organisms), as well as future engagement activities.

Gene Drives: A report on their science, applications, social aspects, ethics and regulations

6670
H. Dressel,  Critical Scientists Switzerland; European Network of Scientists for Social and Environmental Responsibility; Vereinigung Deutscher Wissenschaftler,  2019-05-17 18:00:50.
Engineered Gene Drives are a new form of genetic modification that provides the tools for permanently modifying or potentially even eradicating species or populations in the wild. Unlike the previous genetically modified organisms (GMOs), gene drive organisms (GDOs) are not meant to stay where they are released, but instead are designed and purpose-built to spread and to drive their modified genes far and wide into wild populations.

Gene drives and the international biodiversity regime

18784
F. Rabitz,  Review of European, Comparative & International Environmental Law,  2019-05-17 17:30:54.
Gene drives are genetic modifications designed for rapidly diffusing traits throughout a target population. They are currently being proposed as biological control agents to combat, for instance, invasive alien species and disease vectors. They also raise concerns regarding their potential adverse effects on biological diversity. This text assesses gene drive governance under the Convention on Biological Diversity (CBD) and its Cartagena Protocol on Biosafety. While gene drives are directly relevant for the objectives of both agreements, their regulatory frameworks have not kept up with the pace of technological change. The focus of this article is on the analysis of gaps and inconsistencies within both agreements. It highlights numerous elements of the CBD and the Cartagena Protocol that raise challenges for gene drive governance, such as matters related to regulatory scope, transboundary movements, precaution and invasive alien species.

Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating

11202
J. J. Bull, C. H. Remien and S. M. Krone,  Evolution Medicine and Public Health,  2019:66-81. 2019-05-11 14:03:57.
Genetic engineering combined with CRISPR technology has developed to the point that gene drives can, in theory, be engineered to cause extinction in countless species. Success of extinction programs now rests on the possibility of resistance evolution, which is largely unknown. Depending on the gene-drive technology, resistance may take many forms, from mutations in the nuclease target sequence (e.g. for CRISPR) to specific types of non-random population structures that limit the drive (that may block potentially any gene-drive technology).

Improving plant-resistance to insect-pests and pathogens: The new opportunities through targeted genome editing

6176
D. S. Bisht, V. Bhatia and R. Bhattacharya,  Seminars in Cell & Developmental Biology,  96:65-76. 2019-05-08 18:53:44.
The advantages of high input agriculture are fading away due to degenerating soil health and adverse effects of climate change. Safeguarding crop yields in the changing environment and dynamics of pest and pathogens, has posed new challenges to global agriculture. Thus, integration of new technologies in crop improvement has been imperative for achieving the breeding objectives in faster ways. Recently, enormous potential of genome editing through engineered nucleases has been demonstrated in plants. Continuous refinements of the genome editing tools have increased depth and breadth of their applications. So far, genome editing has been demonstrated in more than fifty plant species. These include model species like Arabidopsis, as well as important crops like rice, wheat, maize etc. Particularly, CRISPR/Cas9 based two component genome editing system has been facile with wider applicability. Potential of genome editing has unfurled enormous possibilities for engineering diverse agronomic traits including durable resistance against insect-pests and pathogens. Novel propositions of developing insect and pathogen resistant crops by genome editing include altering the effector-target interaction, knocking out of host-susceptibility genes, engineering synthetic immune receptor eliciting broad spectrum resistance, uncoupling of antagonistic action of defense hormones etc. Alternatively, modification of insect genomes has been used either to create gene drive or to counteract resistance to various insecticides. The distinct advantage of genome editing system is that it can knock out specific target region in the genome without leaving the unwanted vector backbone. In this article, we have reviewed the novel opportunities offered by the genome editing technologies for developing insect and pathogen resistant crop-types, their future prospects and anticipated challenges.

Identification of fk-1;, a Meiotic Driver Undergoing RNA Editing in Neurospora

15131
N. 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. 2019-05-03 16:12:34.
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 silencing caused by a genome defense process called meiotic silencing by unpaired DNA (MSUD). We show that rfk-1’s MSUD avoidance mechanism is linked to the genomic landscape surrounding the rfk-1 gene, which is located near the Sk-2 border on the right arm of chromosome III. In addition to demonstrating that the location of rfk-1 is critical to spore-killing success, our results add to accumulating evidence that MSUD helps protect Neurospora genomes from complex meiotic drive elements.

RISCOS BIOTECNOLÓGICOS AMBIENTAIS E PARTICIPAÇÃO SOCIAL: POR UMA GESTÃO DEMOCRÁTICA DA BIOTECNOLOGIA GENE DRIVE NA ATUAÇÃO DA CTNBIO

23872
L. C. Rodrigues,  Revista Jurídica (FURB),  22. 2019-03-15 09:15:24.
This research aims to study the way in which the environmental risks of Gene Drive biotechnology challenge forms of effective social participation, inserted in the management of biotechnological risks, whose responsibility lies with the organs linked to the State (CTNBio performance). The method of hypothetical-deductive approach, the method of topical and systematic juridical interpretation and the technique of bibliographic research were used. The conclusion reached was that the need to strengthen the objective sharing of information in an advisory manner to the general public in the face of Gene Drive's biotechnology risks within the framework of the CTNBio from the modification of the current Public Hearings legal model, which gives indications of omissions and lags before the complexity of the theme..

Genetic pest management technologies to control invasive rodents

11576
D. Kanavy and D. Threadgill,  Island invasives: scaling up to meet the challenge,  2019-03-05 15:20:05.
Many strategies exist to manage invasive pests on islands, ranging from poison to trapping, with varying degrees of success. Genetic technologies are increasingly being applied to insect pests, but so far, not to vertebrates. We are implementing a genetic strategy to eradicate invasive mouse populations as another tool for pest control. Mus musculus, the common house mouse, is one of the most widespread invasive species. Mice threaten human health, agriculture, and biodiversity on many islands, particularly seabirds. Seabirds are endangered indirectly through competition for resources or predators being attracted by the mice or directly with mice attacking chicks and eggs. Rodenticides are the most common method of eradicating mice, but their use leads to poisoning of non-target species and has limited efficacy against mice. An approach that could eliminate non-target species impact would be to engineer daughterless mice linked to a gene drive system for self-sustained propagation. For this project, we have investigated exploiting a naturally occurring gene drive, the t-complex. Using the t w2 haplotype of the t-complex, we observed the t w2 haplotype being transmitted to offspring with a transmission distortion ratio of 95.3%. The daughterless phenotype is being accomplished by inserting the Sry gene (male sex-determining gene) into an autosome containing the tw2 haplotype via CRISPR/Cas9 gene editing. The presence of Sry will induce testis formation, regardless of the sex chromosomes naturally inherited. When Sry is inserted into the t-complex, the desired gene will spread through the population, eliminating female offspring. This model system will support studies to evaluate the effectiveness of crashing an invasive population without adversely affecting other

Trialling gene drives to control invasive species: what, where and how?

11573
T. Harvey-Samuel, K. J. Campbell, M. Edgington and L. Alphey,  Island invasives: scaling up to meet the challenge,  2019-03-05 15:16:48.
The control of invasive species would be enhanced through the addition of novel, more effective and sustainable pest management methods. One control option yet to be trialled in the field is to deploy transgene-based ‘Gene Drives’: technologies which force the inheritance of a genetic construct through the gene pool of a wild population, suppressing it or replacing it with a less harmful form. There is considerable interest in applying gene drives to currently intractable invasives across a broad taxonomic range. However, not all species will make efficient or safe targets for these technologies. Additionally, the safety and efficacy of these systems will vary according to where they are deployed, the specific molecular design chosen, and how these factors interact with the ecology of the target pest. Given the transformative but also controversial nature of gene drives, it is imperative that their first field trials are able to successfully demonstrate that they can be used safely and efficiently. Here, we discuss how to maximise the probability of this outcome through considering three important questions: What types of invasive species should we use to trial gene drives? Where should we be trialling them? and How should these trials be conducted? In particular, we focus on the ecological, genetic and geographic features of small, isolated islands which make them ideal locations for these initial trials. A case study of an island invasive that is deemed highly appropriate for gene drive intervention, and for which gene drive development is currently underway (Mus musculus), is used to further explore these concepts

Towards a genetic approach to invasive rodent eradications: assessing reproductive competitiveness between wild and laboratory mice

11570
M. Serr, N. Heard and J. Godwin,  Island invasives: scaling up to meet the challenge,  2019-03-05 15:10:12.
House mice are significant invasive pests, particularly on islands without native mammalian predators. As part of a multi-institutional project aimed at suppressing invasive mouse populations on islands, we aim to create heavily male-biased sex ratios with the goal of causing the populations to crash. Effective implementation of this approach will depend on engineered F1 wild-lab males being effective secondary invaders that can mate successfully. As a first step in assessing this possibility, we are characterising genetic and behavioural differences between Mus musculus strains in terms of mating and fecundity using wild house mice derived from an invasive population on the Farallon Islands (MmF), a laboratory strain C57BL/6/129 (tw2), and F1 wild-lab off spring. Mice with the ‘t allele’ (tw2) have a naturally occurring gene drive system. To assess fertility in F1 wild-lab crosses, tw2 males were paired with wild-derived females from the Farallon Islands (MmF). Results of these matings indicate litter sizes are comparable but that weaned pup and adult wild-lab mice are heavier in mass. Next, we initiated tests of male competitiveness using larger (3 m2 ) enclosures with enrichment. We introduced both an MmF and a tw2-bearing male to two MmF females to assess mating outcomes. Preliminary results of these experiments show none of the offspring carried the t-allele. However, performing the same experiment with F1 wildlab males instead of a full lab background resulted in 70% of off spring carrying the t w2 allele. This indicates that F1 wildlab males may be able to successfully compete and secondarily invade. It will be important in subsequent experiments to determine what characteristics contribute to secondary invasion success. More generally, a better understanding of characteristics contributing to overall success in increasingly complex and naturalistic environments will be critical in determining the potential of a gene drive-based eradication approach for invasive mice on islands

A potential new tool for the toolbox: assessing gene drives for eradicating invasive rodent populations

11550
K. J. Campbell, J. R. Saah, P. R. Brown, J. Godwin, F. Gould, G. R. Howald, A. Piaggio, P. Thomas, D. M. Tompkins, D. Threadgill, J. Delborne, D. Kanavy, T. Kuiken, H. Packard, M. Serr and A. Shiels,  Island invasives: scaling up to meet the challenge,  2019-03-05 14:59:34.
Invasive rodents have significant negative impacts on island biodiversity. All but the smallest of rodent eradications currently rely on island-wide rodenticide applications. Although signifi cant advances have been made in mitigating unintended impacts, rodent eradication on inhabited islands remains extremely challenging. Current tools restrict eradication eff orts to fewer than 15% of islands with critically endangered or endangered species threatened by invasive rodents. The Genetic Biocontrol of Invasive Rodents partnership is an interdisciplinary collaboration to develop and evaluate gene drive technology for eradicating invasive rodent populations on islands. Technological approaches currently being investigated include the production of multiple strains of Mus musculus with a modifi ed form of the native t-complex, or a CRISPR gene drive, carrying genes or mechanisms that determine sex. These systems have the potential to skew the sex ratio of off spring to approach 100% single-sex, which could result in population collapse. One goal proposed is to test the ability of constructs to spread and increase in frequency in M. musculus populations in biosecure, captive settings and undertake modelling to inform development and potential deployment of these systems. Structured ecologically-based risk assessments are proposed, along with social and cultural engagement to assess the acceptability of releasing a gene drive system. Work will be guided by an external ethics advisory board. Partners are from three countries with significant regulatory capacity (USA, Australia, New Zealand). Thus, we will seek data sharing agreements so that results from experiments may be used within all three countries and treat regulatory requirements as a minimum. Species-specific, scalable, and socially acceptable new eradication tools could produce substantial biodiversity benefits not possible with current technologies. Gene drive innovation may provide such a tool for invasive species management and be potentially transformative and worthy of exploring in an inclusive, responsible, and ethical manner.

Meiotic drive shapes rates of karyotype evolution in mammals

5921
Blackmon, H., J. Justison, I. Mayrose and E. E. Goldberg,  Evolution,  73:511-523. 2019-03-01 16:47:19.
Chromosome number is perhaps the most basic characteristic of a genome, yet generalizations that can explain the evolution of this trait across large clades have remained elusive. Using karyotype data from over 1000 mammals, we developed and applied a phylogenetic model of chromosome evolution that links chromosome number changes with karyotype morphology. Using our model, we infer that rates of chromosome number evolution are significantly lower in species with karyotypes that consist of either all bibrachial or all monobrachial chromosomes than in species with a mix of both types of morphologies. We suggest that species with homogeneous karyotypes may represent cases where meiotic drive acts to stabilize the karyotype, favoring the chromosome morphologies already present in the genome. In contrast, rapid bouts of chromosome number evolution in taxa with mixed karyotypes may indicate that a switch in the polarity of female meiotic drive favors changes in chromosome number. We do not find any evidence that karyotype morphology affects rates of speciation or extinction. Furthermore, we document that switches in meiotic drive polarity are likely common and have occurred in most major clades of mammals, and that rapid remodeling of karyotypes may be more common than once thought.

Modulating CRISPR gene drive activity through nucleocytoplasmic localization of Cas9 in S. cerevisiae

18839
M. E. Goeckel, E. M. Basgall, I. C. Lewis, S. C. Goetting, Y. Yan, M. Halloran and G. C. Finnigan,  Fungal Biology Biotechnology,  6:2. 2019-02-16 13:04:41.
In this study, we use artificial gene drives in budding yeast to explore mechanisms to modulate nuclease activity of Cas9 through its nucleocytoplasmic localization. We examine non-native nuclear localization sequences (both NLS and NES) on Cas9 fusion proteins in vivo through fluorescence microscopy and genomic editing. Our results demonstrate that mutational substitutions to nuclear signals and combinatorial fusions can both modulate the level of gene drive activity within a population of cells.

A natural, conditional gene drive in plants

3903
Conner, AJJ, J.M.E.,  bioRxiv,  519884:1-10. 2019-01-21 00:00:00.
A new class of gene drive in plant populations with herbicide resistance is described; a conditional gene drive that operates following herbicide application. Screening progeny from controlled crosses of Brassica napus heterozygous for a dominant allele conferring chlorsulfuron resistance, demonstrated that the herbicide imposes in planta gametic selection against pollen and ovules with the recessive allele for herbicide susceptibility, as well as embryonic selection against embryos homozygous for the susceptible allele. We postulate that natural gene drives are common in plant populations and can operate in a conditional manner resulting in non-Mendelian inheritance in response to abiotic and biotic stresses.

An overview of OECD activities related to modern techniques of biotechnology and genome editing

3923
Kearns, P,  Transgenic Research,  28:41-44. 2019-01-21 00:00:00.
Since commercial use of genetically-engineered (genetically- modified) plants started in 1996, many agricultural products have been developed to improve crop traits. The foods and feeds derived from these commodities have drastically increased worldwide. However, answering health and environmental safety concerns associated with the agricultural use of biotechnology is essential in countries producing the products, as well as in countries using them. To address these concerns, the OECD conducts programmes of work for sharing information, developing tools to facilitate a harmonised approach of risk assessment, and contributing to building consensus between national authorities. This report provides background information on some OECD activities related to safety considerations associated with the use of biotechnology in agriculture (covering applications to crop plants, trees, animals, micro-organisms), including the recent emergence of genome editing techniques.

Genome-wide transcriptome profiling reveals genes associated with meiotic drive system of Aedes aegypti

3943
Shin, DB, K. Susanta; Severson, W. David,  Insects,  10:e25. 2019-01-21 00:00:00.
Aedes aegypti is an important mosquito vector of several arboviruses, including dengue, yellow fever, Zika, and Chikungunya, which cause significant human morbidity and mortality globally. In certain populations of this mosquito, a native meiotic drive system causes abnormal spermatogenesis that results in highly male-biased progenies from some matings. Although the basic genetics and cytogenetics of the drive mechanism were elucidated, very little is known on a transcriptome level about how the meiotic drive phenotype is expressed in individual males. To address this question, we conducted a whole-genome microarray expression study of testes from a meiotic-drive-carrying strain (T37) in comparison with testes from a non-drive-carrying strain (RED). Based on bioinformatics analyses of the microarray data, we identified 209 genes associated with the meiotic drive phenotype that were significantly differentially expressed between the two strains. K-means cluster analysis revealed nine clusters, in which genes upregulated in T37 testes were assigned to five clusters and genes downregulated in T37 testes were assigned to four clusters. Our data further revealed that genes related to protein translation, phosphorylation, and binding, as well as to G-protein-coupled receptor (GPCR) and peptidase activities, are differentially upregulated in testes from males with the meiotic drive genotype. Based on pathway analysis of these differentially expressed genes, it was observed that the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway may play a role in the meiotic drive system. Overall, this investigation enhances our understanding of whole-genome gene expression associated with the meiotic drive system in Ae. aegypti.

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