Scholarly Literature
This is an aggregation of scholarly literature from peer-reviewed journals, bioRxiv , medRxiv and arXiv preprint servers focused on natural and engineered selfish genetic elements and genetic biocontrol. New citations are added as they appear. This content is intended for anyone interested in the scholarly literature on gene drive and genetic biocontrol.
Genome engineering in insects for the control of vector borne diseases
18875V. E. Hillary and S. A. Ceasar, Progress in Molecular Biology and Translational Science, 179:197-223. 2021-10-05 19:22:57.
Insects cause many vector-borne infectious diseases and have become a major threat to human health. Although many control measures are undertaken, some insects are resistant to it, exacerbated by environmental changes which is a major challenge for control measures. Genetic studies by targeting the genomes of insects may offer an alternative strategy. Developments with novel genome engineering technologies have stretched our ability to target and modify any genomic sequence in Eukaryotes including insects. Genome engineering tools such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and most recently discovered, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) systems hold the potential to control the vector-borne diseases. In this chapter, we review the vector control strategy undertaken by employing three major genome engineering tools (ZFNs, TALENs, and CRISPR/Cas9) and discuss the future prospects of this system to control insect vectors. Finally, we also discuss the CRISPR-based gene drive system and its concerns due to ecological impacts.
Towards CRISPR/Cas9-based gene drive in the diamondback moth Plutella xylostella
18867X. Xu, T. Harvey-Samuel, H. Siddiqui, J. Ang, M. A. E. Anderson, C. Reitmayer, E. Lovett, P. T. Leftwich, M. You and L. Alphey, bioRxiv, 2021.10.05.462963. 2021-10-05 19:03:11.
Promising to provide powerful genetic control tools, gene drives have been constructed in multiple dipterans, yeast and mice, for the purposes of population elimination or modification. However, it remains unclear whether these techniques can be applied to lepidopterans. Here, we used endogenous regulatory elements to drive Cas9 and sgRNA expression in the diamondback moth, (Plutella xylostella), and test the first split-drive system in a lepidopteran. The diamondback moth is an economically important global agriculture pest of cruciferous crops and has developed severe resistance to various insecticides, making it a prime candidate for such novel control strategy development. A very high level of somatic editing was observed in Cas9/sgRNA transheterozygotes, although no significant homing was revealed in the subsequent generation. Although heritable, Cas9-medated germline cleavage, as well as maternal and paternal Cas9 deposition was observed, rates were far lower than for somatic cleavage events, indicating robust somatic but limited germline activity of Cas9/sgRNA under the control of selected regulatory elements. Our results provide valuable experience, paving the way for future construction of gene drive-based genetic control strategies in DBM or other lepidopterans.Competing Interest StatementThe authors have declared no competing interest.
Releasing incompatible males drives strong suppression across populations of wild and Wolbachiat-carrying Aedes aegypti in Australia
18844N. W. Beebe, D. Pagendam, B. J. Trewin, A. Boomer, M. Bradford, A. Ford, C. Liddington, A. Bondarenco, P. J. De Barro, J. Gilchrist, C. Paton, K. M. Staunton, B. Johnson, A. J. Maynard, G. J. Devine, L. E. Hugo, G. Rasic, H. Cook, P. Massaro, N. Snoad, J., Proceedings of the National Academy of Sciences, 118:e2106828118. 2021-10-05 11:33:10.
Through replicated treatment and control experiments in northern Australia, regular releases of Aedes aegypti males infected with a Wolbachia from Aedes albopictus was shown to drive strong population suppression in mosaic populations of wild-type (no Wolbachia) and wMel-Wolbachia–carrying Ae. aegypti. In a demonstration of bidirectional incompatibility between different Wolbachia strains in the field, we also demonstrate that one season’s suppression experiment can also show an ongoing effect into the following season.Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the “Debug” Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable
Investigation of Developmental Stage/Age, Gamma Irradiation Dose, and Temperature in Sterilization of Male Aedes aegypti (Diptera: Culicidae) in a Sterile Insect Technique Program
20236B. Ernawan, T. Anggraeni, S. Yusmalinar and I. Ahmad, Journal of Medical Entomology, 59:320-327. 2021-10-01 09:18:43.
The sterilization process using gamma irradiation is a crucial component in a program using sterile insect technique (SIT) to control Aedes aegypti. Unfortunately, there is no efficient standard protocol for sterilizing mosquitoes that can produce a high level of sterility while maintaining mating ability and longevity. Therefore, we conducted a study of the critical factors necessary to develop such a standard protocol. In this study, male Ae. aegypti pupae, as well as adults aged 1 d and 3 d, were irradiated using a Gamma-cell 220 irradiator doses of 0, 20, 40, 60, 70, 80, and 100 Gray (Gy). In addition, male Ae. aegypti in the pupal and adult stage aged 1 d were irradiated at a dose of 70 Gy at various temperatures. Changes in emergence rates, longevity, sterility, and mating competitiveness were recorded for each combination of parameters. Results showed that an in-crease of irradiation dose leads to a rise of induced sterility at all developmental stages, while simultaneously reducing emergence rate, survival, and mating competitiveness. Higher temperatures resulted in increased levels of sterility, reduced longevity, and did not affect the ability to mate. This study found that an irradiation dose of 70 Gy at a temperature between 20.00 and 22.30°C administered in the pupal stage induced a high level of sterility (around 98%), while maintaining mating competitiveness and longevity
Sexual selection can partly explain low frequencies of Segregation Distorter alleles
18815T. A. Keaney, T. M. Jones and L. Holman, Proceedings of the Royal Society B: Biological Sciences, 288:20211190. 2021-09-29 15:21:33.
The Segregation Distorter (SD) allele found in Drosophila melanogaster distorts Mendelian inheritance in heterozygous males by causing developmental failure of non-SD spermatids, such that greater than 90% of the surviving sperm carry SD. This within-individual advantage should cause SD to fix, and yet SD is typically rare in wild populations. Here, we explore whether this paradox can be resolved by sexual selection, by testing if males carrying three different variants of SD suffer reduced pre- or post-copulatory reproductive success. We find that males carrying the SD allele are just as successful at securing matings as control males, but that one SD variant (SD-5) reduces sperm competitive ability and increases the likelihood of female remating. We then used these results to inform a theoretical model; we found that sexual selection could limit SD to natural frequencies when sperm competitive ability and female remating rate equalled the values observed for SD-5. However, sexual selection was unable to explain natural frequencies of the SD allele when the model was parameterized with the values found for two other SD variants, indicating that sexual selection alone is unlikely to explain the rarity of SD.
Life Table of Bactrocera zonata (Saunders) (Diptera: Tephritidae) for Sterile Insect Technique (SIT) in Mauritius
19008R. D. Bhoyroo, S. Facknath and P. Sookar, African Entomology, 29:361-369. 2021-09-28 15:26:50.
Fruit flies (Tephritidae) have been reported to be a serious pest worldwide. In Mauritius, the major fruit fly species of economic and quarantine importance in agricultural production are Bactrocera zonata (Saunders), Zeugodacus cucurbitae (Coquillett) and Bactrocera dorsalis (Hendel). In line with the government's policy for sustainable and organic agriculture under the challenge of climate change, the Sterile Insect Technique (SIT) is being investigated as an alternative to chemical control. For successful cost-effective SIT programme island-wide, the production of competitive and sterile individuals for release is a key requirement. The aim of this study was to investigate the life cycle parameters of B. zonata to evaluate the feasibility of optimum mass rearing of this species. It was observed that B. zonata has a pre-oviposition period of 8 days, an oviposition duration of 51 days, the number of eggs per female along the complete oviposition period was 705 eggs and the peak egg hatchability varied from 88.5 to 91.5 %. The study showed that egg collection could be started as from day 13. The findings demonstrated that 5 weeks of egg collection is optimal for a rearing facility of B. zonata and production cages should be discarded on day 41. It was found that B. zonata has a net reproductive rate of 300.04 females and a mean generation time of 28.73 days. Given a positive Ro and a short T, it can be concluded that mass rearing of B. zonata is economically viable. Within a short period a laboratory population of this species for mass rearing can be established.
A single mutation weakens symbiont-induced reproductive manipulation through reductions in deubiquitylation efficiency
18742J. F. Beckmann, K. Van Vaerenberghe, D. E. Akwa and B. S. Cooper, Proceedings of the National Academy of Sciences, 118:e2113271118. 2021-09-21 14:01:04.
We show that a single naturally observed mutation weakens CI by reducing deubiquitylation. These discoveries help elucidate the molecular basis of symbiont-induced reproductive manipulations.Animals interact with microbes that affect their performance and fitness, including endosymbionts that reside inside their cells. Maternally transmitted Wolbachia bacteria are the most common known endosymbionts, in large part because of their manipulation of host reproduction. For example, many Wolbachia cause cytoplasmic incompatibility (CI) that reduces host embryonic viability when Wolbachia-modified sperm fertilize uninfected eggs. Operons termed cifs control CI, and a single factor (cifA) rescues it, providing Wolbachia-infected females a fitness advantage. Despite CI’s prevalence in nature, theory indicates that natural selection does not act to maintain CI, which varies widely in strength. Here, we investigate the genetic and functional basis of CI-strength variation observed among sister Wolbachia that infect Drosophila melanogaster subgroup hosts. We cloned, Sanger sequenced, and expressed cif repertoires from weak CI–causing wYak in Drosophila yakuba, revealing mutations suspected to weaken CI relative to model wMel in D. melanogaster. A single valine-to-leucine mutation within the deubiquitylating (DUB) domain of the wYak cifB homolog (cidB) ablates a CI-like phenotype in yeast. The same mutation reduces both DUB efficiency in vitro and transgenic CI strength in the fly, each by about twofold. Our results map hypomorphic transgenic CI to reduced DUB activity and indicate that deubiquitylation is central to CI induction in cid systems. We also characterize effects of other genetic variation distinguishing wMel-like cifs. Importantly, CI strength determines Wolbachia prevalence in natural systems and directly influences the efficacy of Wolbachia biocontrol strategies in transinfected mosquito systems. These approaches rely on strong CI to reduce human disease.All study data are included in the article and/or supporting information.
Microsporidia MB is found predominantly associated with Anopheles gambiae s.s and Anopheles coluzzii in Ghana
18931J. Akorli, E. A. Akorli, S. N. A. Tetteh, G. K. Amlalo, M. Opoku, R. Pwalia, M. Adimazoya, D. Atibilla, S. Pi-Bansa, J. Chabi and S. K. Dadzie, Scientific Reports, 11:5. 2021-09-20 19:43:33.
A vertically transmitted microsporidian, Microsporidia MB, with the ability to disrupt Plasmodium development was reported in Anopheles arabiensis from Kenya, East Africa. To demonstrate its range of incidence, archived DNA samples from 7575 Anopheles mosquitoes collected from Ghana were screened. MB prevalence was observed at 1.8%. An. gambiae s.s constituted 87% of positive mosquitoes while the remaining were from An. coluzzii. Both sibling species had similar positivity rates (24% and 19%; p = 0.42) despite the significantly higher number of An. gambiae s.s analysed (An. gambiae s.s = 487; An. coluzzii = 94; p = 0.0005). The microsporidian was also more prevalent in emerged adults from field-collected larvae than field-caught adults (p < 0.0001) suggestive of an efficient vertical transmission and/or horizontal transfer among larvae. This is the first report of Microsporidia MB in Anopheles mosquitoes in West Africa. It indicates possible widespread among malaria vector species and warrants investigations into the symbiont's diversity across sub-Saharan Africa.
Discrete dynamical models on Wolbachia infection frequency in mosquito populations with biased release ratios
18717Y. Shi and B. Zheng, Journal of Biological Dynamics, 2021-09-18 14:11:29.
We develop two discrete models to study how supplemental releases affect the Wolbachia spreading dynamics in cage mosquito populations. The first model focuses on the case when only infected males are released at each generation. This release strategy has been proved to be capable of speeding up the Wolbachia persistence by suppressing the compatible matings between uninfected individuals. The second model targets the case when only infected females are released at each generation. For both models, detailed model formulation, enumeration of the positive equilibria and their stability analysis are provided. Theoretical results show that the two models can generate bistable dynamics when there are three positive equilibrium points, semi-stable dynamics for the case of two positive equilibrium points. And when the positive equilibrium point is unique, it is globally asymptotically stable. Some numerical simulations are offered to get helpful implications on the design of the release strategy.
Symbiotic Interactions Between Mosquitoes and Mosquito Viruses
18715M. Altinli, E. Schnettler and M. Sicard, Front Cell Infect Microbiol, 11:694020. 2021-09-17 14:06:45.
Mosquitoes not only transmit human and veterinary pathogens called arboviruses (arthropod-borne viruses) but also harbor mosquito-associated insect-specific viruses (mosquito viruses) that cannot infect vertebrates. In the past, studies investigating mosquito viruses mainly focused on highly pathogenic interactions that were easier to detect than those without visible symptoms. However, the recent advances in viral metagenomics have highlighted the abundance and diversity of viruses which do not generate mass mortality in host populations. Over the last decade, this has facilitated the rapid growth of virus discovery in mosquitoes. The circumstances around the discovery of mosquito viruses greatly affected how they have been studied so far. While earlier research mainly focused on the pathogenesis caused by DNA and some double-stranded RNA viruses during larval stages, more recently discovered single-stranded RNA mosquito viruses were heavily studied for their putative interference with arboviruses in female adults. Thus, many aspects of mosquito virus interactions with their hosts and host-microbiota are still unknown. In this context, considering mosquito viruses as endosymbionts can help to identify novel research areas, in particular in relation to their long-term interactions with their hosts (e.g. relationships during all life stages, the stability of the associations at evolutionary scales, transmission routes and virulence evolution) and the possible context-dependent range of interactions (i.e. beneficial to antagonistic). Here, we review the symbiotic interactions of mosquito viruses considering different aspects of their ecology, such as transmission, host specificity, host immune system and interactions with other symbionts within the host cellular arena. Finally, we highlight related research gaps in mosquito virus research.
Predicting the spread and persistence of genetically modified dominant sterile male mosquitoes
18680A. Ickowicz, S. D. Foster, G. R. Hosack and K. R. Hayes, Parasites and Vectors, 14:480. 2021-09-16 13:03:47.
Reproductive containment provides an opportunity to implement a staged-release strategy for genetic control of malaria vectors, in particular allowing predictions about the spread and persistence of (self-limiting) sterile and male-biased strains to be compared to outcomes before moving to (self-sustaining) gene-drive strains. In this study, we: (i) describe a diffusion–advection–reaction model of the spread and persistence of a single cohort of male mosquitoes; (ii) elicit informative prior distributions for model parameters, for wild-type (WT) and genetically modified dominant sterile strains (DSM); (iii) estimate posterior distributions for WT strains using data from published mark-recapture-release (MRR) experiments, with inference performed through the Delayed-Rejection Adaptive Metropolis algorithm; and (iv) weight prior distributions, in order to make predictions about genetically modified strains using Bayes factors calculated for the WT strains. If a single cohort of 5000 genetically modified dominant sterile male mosquitoes are released at the same location as previous MRR experiments with their WT counterparts, there is a 90% probability that the expected number of released mosquitoes will fall to < 1 in 10 days, and that by 12 days there will be a 99% probability that no mosquitoes will be found more than 150 m from the release location. Spread and persistence models should form a key component of risk assessments of novel genetic control strategies for malaria vectors. Our predictions, used in an independent risk assessment, suggest that genetically modified sterile male mosquitoes will remain within the locality of the release site, and that they will persist for a very limited amount of time. Data gathered following the release of these mosquitoes will enable us to test the accuracy of these predictions and also provide a means to update parameter distributions for genetic strains in a coherent (Bayesian) framework. We anticipate this will provide additional insights about how to conduct probabilistic risk assessments of stage-released genetically modified mosquitoes.
Novel Sterile Insect Technology Program Results in Suppression of a Field Mosquito Population and Subsequently to Reduced Incidence of Dengue
30892Lisiane de Castro Poncio, Filipe Apolinário dos Anjos, Deborah A de Oliveira, Débora Rebechi, et al., The Journal of Infectious Diseases, 224:1005-1014. 2021-09-15 08:29:17.
There is a steady rise in the global incidence of Aedes-borne arbovirus disease. It has become urgent to develop alternative solutions for mosquito vector control. We developed a new method of sterilization of male mosquitoes with the goal to suppress a local Aedes aegypti population and to prevent the spread of dengue. Sterile male mosquitoes were produced from a locally acquired Ae. aegypti colony by using a treatment that includes double-stranded RNA and thiotepa. A field study was conducted with sterile mosquito releases being performed on a weekly basis in predefined areas. There were 2 intervention periods (INT1 and INT2), with treatment and control areas reversed between INT1 and INT2. During INT1, releases in the treated area resulted in up to 91.4% reduction of live progeny of field Ae. aegypti mosquitoes recorded over time, while the control neighborhoods (no releases of sterile male mosquitoes) remained highly infested. The successful implementations of the program during INT1 and INT2 were associated with 15.9-fold and 13.7-fold lower incidences of dengue in the treated area compared to the control areas, respectively. Our data show the success of this new sterile insect technology-based program in preventing the spread of dengue.
Evolutionary robustness of killer meiotic drives
18676P. G. Madgwick and J. B. Wolf, Evolution Letters, 2021-09-12 12:53:08.
A meiotic driver is a selfish genetic element that interferes with the process of meiosis to promote its own transmission. The most common mechanism of interference is gamete killing, where the meiotic driver kills gametes that do not contain it. A killer meiotic driver is predicted to spread rapidly through a population at the expense of other genes in the rest of the genome. The rapid spread of a killer meiotic driver is expected to be chased by the rapid spread of a suppressor that returns fair meiosis. Paradoxically, while this might imply that meiotic drivers should be evolutionarily transient, numerous ancient killer meiotic drivers have been discovered that have persisted for millions of years. To understand the rationale that could potentially explain such evolutionary robustness, we explore different possible mechanisms of killer meiotic drive and the different possible associated mechanisms of suppression. We use a framework that considers how the different stages of meiosis result in different structured interactions among cells with different genotypes in various combinations. Across possible interactions, we show that there are three genotypically distinct drive mechanisms that create alternative selective conditions for the spread of different types of suppressors. We show that killer meiotic drivers are more evolutionarily robust if they operate among sister cells (after meiosis I and before meiosis II) than at any other point during meiosis. The different drive mechanisms we identify make testable predictions that could explain why some killer meiotic drivers are transient while others are ancient.
Suppressing mosquito populations with precision guided sterile males
18513M. Li, T. Yang, M. Bui, S. Gamez, T. Wise, N. P. Kandul, J. Liu, L. Alcantara, H. Lee, J. R. Edula, R. Raban, Y. Zhan, Y. Wang, N. DeBeaubien, J. Chen, H. M. Sánchez C, J. B. Bennett, I. Antoshechkin, C. Montell, J. M. Marshall and O. S. Akbari, Nature Communications, 12:5374. 2021-09-10 14:42:45.
The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.
Two newly introduced Wolbachia endosymbionts induce cell host differences in competitiveness and metabolic responses
18510T. P. Li, S. S. Zha, C. Y. Zhou, X. Xia, A. A. Hoffmann and X. Y. Hong, Appl Environ Microbiol, Aem0147921. 2021-09-09 14:34:33.
Wolbachia endosymbionts can induce multiple reproductive manipulations in their hosts, with cytoplasmic incompatibility (CI) being one of the most common manipulations. The important agricultural pests, white-backed planthopper (Sogatella furcifera) and brown planthopper (Nilaparvata lugens), are usually infected with CI-inducing Wolbachia wFur and non-CI-inducing Wolbachia wLug, respectively. The biological effects of these infections when present in a host cell are unknown. Here, we introduced the two Wolbachia strains into an Aedes albopictus cell line to stably establish a wFur-infected cell line (WFI) and a wLug-infected cell line (WLI). In a mixed culture, WFI cells were completely replaced by WLI cells, pointing to a stronger competitiveness of the WLI cell line. We found that infection by both Wolbachia strains reduced cell growth rates, but WLI had a faster cell growth rate than WFI, and this difference in cell growth rate combined with possible Wolbachia differences in diffusivity may have affected cell competitiveness. By examining gene expression and metabolites in the two lines, we found that some genes and key metabolites responded to differences in cell competitiveness. These results point to potential mechanisms that could contribute to the relative performance of hosts infected by these strains and also highlight the substantial impact of a non-CI Wolbachia on metabolism, which may in turn influence fitness of its native host. IMPORTANCE Wolbachia transinfection in insects can be used to suppress pests and block virus transmission. We stably introduced two Wolbachia strains from rice planthoppers into cell lines of an important arbovirus mosquito vector, Aedes albopictus. The competitiveness of host cells from the lines infected by the two Wolbachia strains was different, as were metabolic responses of the cell lines. These results suggest potential metabolic effects of Wolbachia on native hosts which could be exploited when they are transinfected into novel hosts for pest control.
A supernumerary “B-sex” chromosome drives male sex determination in the Pachón cavefish, Astyanax mexicanus
18508B. Imarazene, K. Du, S. Beille, E. Jouanno, R. Feron, Q. Pan, J. Torres-Paz, C. Lopez-Roques, A. Castinel, L. Gil, C. Kuchly, C. Donnadieu, H. Parrinello, L. Journot, C. Cabau, M. Zahm, C. Klopp, T. Pavlica, A. Al-Rikabi, T. Liehr, S. A. Simanovsky, J. Bo, Current Biology, 2021-09-09 14:28:39.
Sex chromosomes are generally derived from a pair of classical type-A chromosomes, and relatively few alternative models have been proposed up to now.(1)(,)(2) B chromosomes (Bs) are supernumerary and dispensable chromosomes with non-Mendelian inheritance found in many plant and animal species(3)(,)(4) that have often been considered as selfish genetic elements that behave as genome parasites.(5)(,)(6) The observation that in some species Bs can be either restricted or predominant in one sex(7-14) raised the interesting hypothesis that Bs could play a role in sex determination.(15) The characterization of putative B master sex-determining (MSD) genes, however, has not yet been provided to support this hypothesis. Here, in Astyanax mexicanus cavefish originating from Pachón cave, we show that Bs are strongly male predominant. Based on a high-quality genome assembly of a B-carrying male, we characterized the Pachón cavefish B sequence and found that it contains two duplicated loci of the putative MSD gene growth differentiation factor 6b (gdf6b). Supporting its role as an MSD gene, we found that the Pachón cavefish gdf6b gene is expressed specifically in differentiating male gonads, and that its knockout induces male-to-female sex reversal in B-carrying males. This demonstrates that gdf6b is necessary for triggering male sex determination in Pachón cavefish. Altogether these results bring multiple and independent lines of evidence supporting the conclusion that the Pachón cavefish B is a "B-sex" chromosome that contains duplicated copies of the gdf6b gene, which can promote male sex determination in this species.
Persistent Spodoptera frugiperda rhabdovirus infection in Sf9 cells is not restricted by Wolbachia wMelPop-CLA and wAlbB strains and is targeted by the RNAi machinery
18362R. Parry, H. de Malmanche and S. Asgari, Virology, 563:82-87. 2021-09-08 14:28:58.
The endosymbiotic bacterium Wolbachia pipientis confers RNA virus refractoriness in Drosophila and Aedes mosquitoes. Questions remain about the Wolbachia-virus restriction phenotype and how extensive this phenomenon may be within other arthropods. Here, we generated two Spodoptera frugiperda cell lines stably transinfected with two strains of Wolbachia, wAlbB and wMelPop-CLA. Despite the high density of Wolbachia in stably infected Sf9 cells, RT-PCR indicated the presence of the negative-sense RNA virus Spodoptera frugiperda rhabdovirus (SfRV) in Wolbachia-infected and uninfected cell lines. No differences in the replication of SfRV between Sf9 and Wolbachia-infected cells was found. RNA-Seq analysis of the parental Sf9 cells supported SfRV's presence in these cells with abundant 20 nt virus-derived small RNAs indicating active replication of SfRV in these cells. Overall, this study supports a growing body of evidence that Wolbachia does not restrict negative-sense RNA viruses and generates an in vitro model to examine Lepidoptera-Wolbachia virus interactions.
Wolbachia-Conferred Antiviral Protection Is Determined by Developmental Temperature
18357E. Chrostek, N. Martins, M. S. Marialva and L. Teixeira, mBio, e0292320. 2021-09-08 14:13:12.
Overall, we show that Wolbachia-conferred antiviral protection is temperature dependent, being present or absent depending on the environmental conditions. This interaction likely impacts Wolbachia-host interactions in nature and, as a result, frequencies of host and symbionts in different climates. Dependence of Wolbachia-mediated pathogen blocking on developmental temperature could be used to dissect the mechanistic bases of protection and influence the deployment of Wolbachia to prevent transmission of arboviruses. IMPORTANCE Insects are often infected with beneficial intracellular bacteria. The bacterium Wolbachia is extremely common in insects and can protect them from pathogenic viruses. This effect is being used to prevent transmission of dengue and Zika viruses by Wolbachia-infected mosquitoes. To understand the biology of insects in the wild, we need to discover which factors affect Wolbachia-conferred antiviral protection. Here, we show that the temperature at which insects develop from eggs to adults can determine the presence or absence of antiviral protection. The environment, therefore, strongly influences this insect-bacterium interaction. Our work may help to provide insights into the mechanism of viral blocking by Wolbachia, deepen our understanding of the geographical distribution of host and symbiont, and incentivize further research on the temperature dependence of Wolbachia-conferred protection for control of mosquito-borne disease.
Diverse wMel variants of Wolbachia pipientis differentially rescue fertility and cytological defects of the bag of marbles partial loss of function mutation in Drosophila melanogaster
18817J. E. Bubnell, P. Fernandez-Begne, C. K. S. Ulbing and C. F. Aquadro, G3 Genes|Genomes|Genetics, 2021-09-07 15:29:22.
In Drosophila melanogaster, the maternally inherited endosymbiont Wolbachia pipientis interacts with germline stem cell genes during oogenesis. One such gene, bag of marbles (bam) is the key switch for differentiation and also shows signals of adaptive evolution for protein diversification. These observations have led us to hypothesize that W. pipientis could be driving the adaptive evolution of bam for control of oogenesis. To test this hypothesis, we must understand the specificity of the genetic interaction between bam and W. pipientis. Previously, we documented that the W. pipientis variant, wMel, rescued the fertility of the bamBW hypomorphic mutant as a transheterozygote over a bam null. However, bamBW was generated more than 20 years ago in an uncontrolled genetic background and maintained over a balancer chromosome. Consequently, the chromosome carrying bamBW accumulated mutations that have prevented controlled experiments to further assess the interaction. Here, we used CRISPR/Cas9 to engineer the same single amino acid bam hypomorphic mutation (bamL255F) and a new bam null disruption mutation into the w1118 isogenic background. We assess the fertility of wildtype bam, bamL255F/bamnull hypomorphic, and bamL255F/bamL255F mutant females, each infected individually with 10 W. pipientis wMel variants representing three phylogenetic clades. Overall, we find that all of the W. pipientis variants tested here rescue bam hypomorphic fertility defects with wMelCS-like variants exhibiting the strongest rescue effects. In addition, these variants did not increase wildtype bam female fertility. Therefore, both bam and W. pipientis interact in genotype-specific ways to modulate female fertility, a critical fitness phenotype.
Assessment of fitness and vector competence of a New Caledonia wMel Aedes aegypti strain before field-release
18360N. Pocquet, O. O’Connor, H. A. Flores, J. Tutagata, M. Pol, D. J. Hooker, C. Inizan, S. Russet, J. M. Duyvestyn, E. C. Pacidônio, D. Girault, D. da Silva Gonçalves, M. Minier, F. Touzain, E. Chalus, K. Lucien, F. Cheilan, T. Derycke, S. Laumond, C. P. Sim, PLOS Neglected Tropical Diseases, 15:e0009752. 2021-09-07 14:13:26.
Dengue represents a risk for almost half of the world’s population, especially throughout the tropics. In New Caledonia, dengue outbreaks have become more frequent in the past decade along with the recent circulation of chikungunya and Zika viruses. The opportunity to use the biocontrol method involving the release of Wolbachia-infected Ae. aegypti mosquitoes has been investigated as an alternative solution to the traditional control methods, like elimination of larval habitats and pyrethroid insecticide application to kill adults, which are becoming insufficient. A local strain of Ae. aegypti carrying Wolbachia (NC-wMel) has been generated and tested to evaluate its pathogen blocking capacity for the four dengue virus serotypes as well as chikungunya and Zika viruses. The fitness of NC-wMel strain has also been assessed to estimate its ability to compete with the wild-type strain in the field. Noumea city, where a third of the population of New Caledonia resides, has been chosen as the first site to implement the method in New Caledonia. As Ae. aegypti is the only proven vector in New Caledonia, we expect a significant impact on dengue outbreaks occurring in Noumea as soon as a high frequency of NC-wMel is established in the population.
Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila
18354C. A. Muirhead and D. C. Presgraves, Nature Ecology & Evolution, 2021-09-06 14:01:24.
Sex chromosomes are susceptible to the evolution of selfish meiotic drive elements that bias transmission and distort progeny sex ratios. Conflict between such sex-ratio drivers and the rest of the genome can trigger evolutionary arms races resulting in genetically suppressed ‘cryptic’ drive systems. The Winters cryptic sex-ratio drive system of Drosophila simulans comprises a driver, Distorter on the X (Dox) and an autosomal suppressor, Not much yang, a retroduplicate of Dox that suppresses via production of endogenous small interfering RNAs (esiRNAs). Here we report that over 22 Dox-like (Dxl) sequences originated, amplified and diversified over the ~250,000-year history of the three closely related species, D. simulans, D. mauritiana and D. sechellia. The Dxl sequences encode a rapidly evolving family of protamines. Dxl copy numbers amplified by ectopic exchange among euchromatic islands of satellite DNAs on the X chromosome and separately spawned four esiRNA-producing suppressors on the autosomes. Our results reveal the genomic consequences of evolutionary arms races and highlight complex interactions among different classes of selfish DNAs.
The viral era
18352B. Giese, EMBO reports, 22:e53229. 2021-09-06 13:54:36.
New biotechnologies such as gene drives and engineered viruses herald a viral era that would give humans exceptional power over any organism at the level of the genotype. In synthetic biology, orthogonality—in the sense of lack of interference—between different systems or system components is sought for new creations. Current approaches to controlling gene drives also aim for orthogonality, but at a higher level of organisms, populations and species. To keep information under control, orthogonality and reversibility have to be guaranteed before any releases. As with chemical substances, where persistence and bioaccumulation are reasons for concern, the same should apply to genetic information released into nature
Mosquito transgenesis for malaria control
18284S. Dong, Y. Dong, M. L. Simões and G. Dimopoulos, Trends in Parasitology, 2021-09-02 14:42:32.
Malaria is one of the deadliest diseases. Because of the ineffectiveness of current malaria-control methods, several novel mosquito vector-based control strategies have been proposed to supplement existing control strategies. Mosquito transgenesis and gene drive have emerged as promising tools for preventing the spread of malaria by either suppressing mosquito populations by self-destructing mosquitoes or replacing mosquito populations with disease-refractory populations. Here we review the development of mosquito transgenesis and its application for malaria control, highlighting the transgenic expression of antiparasitic effector genes, inactivation of host factor genes, and manipulation of miRNAs and lncRNAs. Overall, from a malaria-control perspective, mosquito transgenesis is not envisioned as a stand-alone approach; rather, its use is proposed as a complement to existing vector-control strategies.
wMel Wolbachia genome remains stable after 7 years in Australian Aedes aegypti field populations
18281K. R. Dainty, J. Hawkey, L. M. Judd, E. C. Pacidônio, J. M. Duyvestyn, D. S. Gonçalves, S. Y. Lin, T. B. O'Donnell, S. L. O'Neill, C. P. Simmons, K. E. Holt and H. A. Flores, Microbial Genomics, 7. 2021-09-02 14:23:53.
Infection of wMel Wolbachia in Aedes aegypti imparts two signature features that enable its application for biocontrol of dengue. First, the susceptibility of mosquitoes to viruses such as dengue and Zika is reduced. Second, a reproductive manipulation is caused that enables wMel introgression into wild-type mosquito populations. The long-term success of this method relies, in part, on evolution of the wMel genome not compromising the critical features that make it an attractive biocontrol tool. This study compared the wMel Wolbachia genome at the time of initial releases and 1-7 years post-release in Cairns, Australia. Our results show the wMel genome remains highly conserved up to 7 years post-release in gene sequence, content, synteny and structure. This work suggests the wMel genome is stable in its new mosquito host and, therefore, provides reassurance on the potential for wMel to deliver long-term public-health impacts.
Unravelling the mystery of female meiotic drive: where we are
18263F. E. Clark and T. Akera, Open Biol, 11:210074. 2021-09-02 13:30:18.
Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.
Gene drive escape from resistance depends on mechanism and ecology
18261F. Cook, J. J. Bull and R. Gomulkiewicz, bioRxiv, 2021.08.30.458221. 2021-08-31 13:20:26.
Gene drives can potentially be used to suppress pest populations, and the advent of CRISPR technology has made it feasible to engineer them in many species, especially insects. What remains largely unknown for implementations is whether anti-drive resistance will evolve to block the population suppression. An especially serious threat to some kinds of drive is mutations in the CRISPR cleavage sequence that block the action of CRISPR, but designs have been proposed to avoid this type of resistance. Various types of resistance at loci away from the cleavage site remain a possibility, which is the focus here. It is known that modest-effect suppression drives can essentially `outrun' unlinked resistance even when that resistance is present from the start. We demonstrate here how the risk of evolving (unlinked) resistance can be further reduced without compromising overall suppression by introducing multiple suppression drives or by designing drives with specific ecological effects. However, we show that even modest-effect suppression drives remain vulnerable to the evolution of extreme levels of inbreeding, which halt the spread of the drive without actually interfering with its mechanism. The landscape of resistance evolution against suppression drives is therefore complex, but avenues exist for enhancing gene drive success.Competing Interest StatementThe authors have declared no competing interest.
The international governance of gene drive organisms
18320F. Rabitz, Environmental Politics, 2021-08-29 13:07:16.
Gene Drive Organisms (GDOs) are a proposed biotechnological intervention that might generate significant benefits for the conservation and sustainable use of biological diversity while also raising critical biosafety issues. Despite their inevitable transboundary effects, their implications for international institutions remain undertheorized. This text develops a theoretical analysis of international GDO governance. First, it elaborates the problem-structural characteristics of GDOs that turn them into a novel and distinct governance challenge, focusing on leverage, cost-benefit distributions, irreversibility, as well as uncertainty and unpredictability. Second, it derives the implications of problem structure for institutional design by focusing on pre-release risk assessment and authorization, as well as post-release monitoring and liability. Third, it uses these institutional implications for benchmarking the Cartagena Protocol on Biosafety, the focal point in international biotechnology regulation, for effective GDO governance. The text concludes that institutional reforms are required for folding GDOs into international biodiversity policy.
Flavors of Non-Random Meiotic Segregation of Autosomes and Sex Chromosomes
18819F. Pajpach, T. Wu, L. Shearwin-Whyatt, K. Jones and F. Grützner, Genes, 12. 2021-08-28 15:33:36.
Segregation of chromosomes is a multistep process occurring both at mitosis and meiosis to ensure that daughter cells receive a complete set of genetic information. Critical components in the chromosome segregation include centromeres, kinetochores, components of sister chromatid and homologous chromosomes cohesion, microtubule organizing centres, and spindles. Based on the cytological work in the grasshopper Brachystola, it has been accepted for decades that segregation of homologs at meiosis is fundamentally random. This ensures that alleles on chromosomes have equal chance to be transmitted to progeny. At the same time mechanisms of meiotic drive and an increasing number of other examples of non-random segregation of autosomes and sex chromosomes provide insights into the underlying mechanisms of chromosome segregation but also question the textbook dogma of random chromosome segregation. Recent advances provide a better understanding of meiotic drive as a prominent force where cellular and chromosomal changes allow autosomes to bias their segregation. Less understood are mechanisms explaining observations that autosomal heteromorphism may cause biased segregation and regulate alternating segregation of multiple sex chromosome systems or translocation heterozygotes as an extreme case of non-random segregation. We speculate that molecular and cytological mechanisms of non-random segregation might be common in these cases and that there might be a continuous transition between random and non-random segregation which may play a role in the evolution of sexually antagonistic genes and sex chromosome evolution.
Parallel pathways for recruiting effector proteins determine centromere drive and suppression
18266T. Kumon, J. Ma, R. B. Akins, D. Stefanik, C. E. Nordgren, J. Kim, M. T. Levine and M. A. Lampson, Cell, 2021-08-26 13:45:10.
Selfish centromere DNA sequences bias their transmission to the egg in female meiosis. Evolutionary theory suggests that centromere proteins evolve to suppress costs of this "centromere drive." In hybrid mouse models with genetically different maternal and paternal centromeres, selfish centromere DNA exploits a kinetochore pathway to recruit microtubule-destabilizing proteins that act as drive effectors. We show that such functional differences are suppressed by a parallel pathway for effector recruitment by heterochromatin, which is similar between centromeres in this system. Disrupting the kinetochore pathway with a divergent allele of CENP-C reduces functional differences between centromeres, whereas disrupting heterochromatin by CENP-B deletion amplifies the differences. Molecular evolution analyses using Murinae genomes identify adaptive evolution in proteins in both pathways. We propose that centromere proteins have recurrently evolved to minimize the kinetochore pathway, which is exploited by selfish DNA, relative to the heterochromatin pathway that equalizes centromeres, while maintaining essential functions.
Versatile Applications of the CRISPR/Cas Toolkit in Plant Pathology and Disease Management
19445M. S. Wheatley and Y. N. Yang, Phytopathology, 111:1080-1090. 2021-08-25 21:11:15.
New tools and advanced technologies have played key roles in facilitating basic research in plant pathology and practical approaches for disease management and crop health. Recently. the CRISPR/Cas (clustered regularly interspersed short palindromic repeats/CRISPR-associated) system has emerged as a powerful and versatile tool for genome editing and other molecular applications. This review aims to introduce and highlight the CRISPR/Cas toolkit and its current and future impact on plant pathology and disease management. We will cover the rapidly expanding horizon of various CRISPR/Cas applications in the basic study of plant-pathogen interactions, genome engineering of plant disease resistance, and molecular diagnosis of diverse pathogens. Using the citrus greening disease as an example, various CRISPR/Cas-enabled strategies are presented to precisely edit the host genome for disease resistance, to rapidly detect the pathogen for disease management, and to potentially use gene drive for insect population control. At the cutting edge of nucleic acid manipulation and detection, the CRISPR/Cas toolkit will accelerate plant breeding and reshape crop production and disease management as we face the challenges of 21st century agriculture.
Sterile males and females can synergistically suppress wild pests targeted by sterile insect technique
18837Y. Ikegawa, K. Ito, C. Himuro and A. Honma, Journal of Theoretical Biology, 530. 2021-08-23 11:21:38.
We constructed a mathematical model to examine the contribution of sterile males and females to the pest-control effect and the synergy between them. We consider that males seek out and court females in accord with their own female searching ability and preference, and that females subsequently choose one male from among males courting them in accordance with their own preference. Using this model, we compared the pest-control effect of bisexual and unisexual release, focusing on the difference in mating systems of the targeted insects. We showed that for swarm-type mating systems (with few courtship chances with higher encounter rates), bisexual release was the most effective, irrespective of the relative female searching ability between wild and sterile males. In this case, sterile females indirectly reduce wild females mating with either male by absorbing courtship from both wild and sterile males. By contrast, bisexual release is the most effective for scramble-type mating systems (more courtship chances with lower encounter rates) only when the female searching ability of sterile males is lower than that of wild males. In this case, sterile females absorb courtship from males with higher searching abilities. Therefore, the net impact of sterile females depends on the difference in sexual performance between wild and sterile males. Because the sexual performance of sterile insects is often degraded during the process of sterilization, we suggest that bisexual release can be a compatible measure to efficiently suppress wild pest populations.
Cas9-Mediated Gene-Editing in the Black-Legged Tick, Ixodes Scapularis, by Embryo Injection and ReMOT Control.
17197A. a. P. Sharma, Michael N. and Reyes, Jeremiah B. and Chana, Randeep and Yim, Won C. and Heu, Chan C. and Kim, Donghun and Chaverra-Rodriguez, Duverney and Rasgon, Jason L. and Harrell, Robert A. and Nuss, Andrew B. and Gulia-Nuss, Monika,, Cell Reports, 2021-08-20 20:35:08.
Despite their capacity to acquire and pass on an array of debilitating pathogens, research on ticks has lagged behind other arthropod vectors, such as mosquitoes, largely because of a lack of genetic and molecular tools. CRISPR-Cas9 is transforming non-model organism research; however, successful gene editing has not yet been reported in ticks. Technical challenges for injecting tick embryos to attempt gene editing have further slowed research progress. Herein we report a successful tick embryo injection protocol for the black-legged tick, Ixodes scapularis, the first for any chelicerate species, and the use of this protocol for genome editing with CRISPR-Cas9. We also demonstrated for the first time that the ReMOT Control technique can be successfully used to generate genome mutations outside Insecta. Our results provide innovative tools to the tick research community that are essential for advancing our understanding of the molecular mechanisms governing pathogen transmission by tick vectors as well as for understanding the underlying biology of host-vector-pathogen interactions.
CRISPR/Cas9-based functional characterization of the pigmentation gene ebony in Plutella xylostella
18155X. Xu, T. Harvey-Samuel, J. Yang, M. You and L. Alphey, Insect Molecular Biology, 2021-08-20 17:59:44.
Abstract Body pigmentation is an important character of insects in adapting to biotic and abiotic environmental challenges. Additionally, based on the relative ease of screening, several genes involved in insect melanisation have been used in classic genetic studies or as visual markers in constructing transgenic insects. Here, a homolog of the Bombyx mori melanisation-inhibiting gene ebony, associated with the conversion of dopamine to N-?-alanyl dopamine, was identified in a global pest, Plutella xylostella. The CRISPR/Cas9 system was applied to generate multiple Pxebony knockout alleles which were crossed to produce a Pxebony knockout strain, showing darker pigmentation in larvae, pupae and adults, compared with wildtype. Interestingly, we observed that Pxebony heterozygotes displayed an intermediate darkened phenotype, indicating partial dominance between the knockout and wildtype alleles. The fitness costs of Pxebony-deficiency were also assessed in the mutant strain, indicating that embryo hatchability and larval survival were significantly reduced, while the eclosion rate was not obviously affected. Our work provides a potential target for exploring CRISPR-based genetics-control systems in this economically important pest lepidopteran.
Insect pest management in the age of synthetic biology
18682R. Mateos Fernández, M. Petek, I. Gerasymenko, M. Juteršek, Š. Baebler, K. Kallam, E. Moreno Giménez, J. Gondolf, A. Nordmann, K. Gruden, D. Orzaez and N. J. Patron, Plant Biotechnology Journal, 2021-08-20 13:09:26.
Arthropod crop pests are responsible for 20% of global annual crop losses, a figure predicted to increase in a changing climate where the ranges of numerous species are projected to expand. At the same time, many insect species are beneficial, acting as pollinators and predators of pest species. For thousands of years, humans have used increasingly sophisticated chemical formulations to control insect pests but, as the scale of agriculture expanded to meet the needs of the global population, concerns about the negative impacts of agricultural practices on biodiversity have grown. While biological solutions, such as biological control agents and pheromones, have previously had relatively minor roles in pest management, biotechnology has opened the door to numerous new approaches for controlling insect pests. In this review, we look at how advances in synthetic biology and biotechnology are providing new options for pest control. We discuss emerging technologies for engineering resistant crops and insect populations and examine advances in biomanufacturing that are enabling the production of new products for pest control.
New mosquito control tools are critical
18148L. Braack, Open Access Government, 2021-08-17 17:38:18.
Globally, we are making slow headway in the fight against malaria, but there has been progress, nonetheless. Since 2000, 39 countries and territories have managed to rid themselves of malaria; the most recent is China. Existing tools can achieve local elimination, but the battle is becoming harder and mosquitoes and parasites are able to change their defences, which is why we too have to constantly adapt and respond with better tools and strategies. We should also be on high alert; malaria has been distracting our attention from what will be our next global public health threat: mosquito-borne arboviruses such as Dengue, Chikungunya, Zika, Yellow Fever, West Nile Virus, Usutu, and a host of others few people have heard of. These arboviruses are spreading across the globe, each year more abundant. The mosquitoes that transmit them pose a different set of challenges, as most of them bite by day, with very different breeding habits. We must increase public awareness of the rising threat and invest much greater research effort to find ways to combat these viruses and mosquitoes.
Genetically Modified Mosquitoes
18286E. P. Caragata, Y. Lee and E. A. Buckner, UF IFAS Extension Service, 2021-08-17 14:49:18.
Genetically modified (GM) mosquitoes are controversial, partly because of misinformation. This publication provides science-based information about GM mosquitoes to the public and anyone involved in mosquito control. It explains what GM mosquitoes are and why they are being investigated as a tool for mosquito control. Describes a GM mosquito pilot project in Florida, and includes FAQs and answers explaining how GM mosquitoes are created and their potential impacts on people and the environment.
A Monte Carlo study to investigate the feasibility to use the Moroccan panoramic irradiator in sterile insect technique programs
18159A. Aknouch, Y. El-ouardi, L. Hamroud, R. Sebihi, M. Mouhib, M. Yjjou, A. Didi and A. Choukri, Radiation and Environmental Biophysics, 2021-08-14 18:10:19.
Mediterranean fly pest (Ceratitis) is one of the most destructive pests of fruit species in Morocco. The sterile insect technique (SIT) is an environmentally friendly strategy that uses ionizing radiation to sterilize adult insects. Morocco has a panoramic gamma irradiator used to irradiate agri-food products. This irradiator is not dedicated to SIT programs due to its geometry that does not allow to obtain a dose uniformity ratio (DUR) recommended for such applications. This article presents a Monte Carlo study to investigate the feasibility of using the panoramic gamma irradiator at the National Institute for Agronomic Research (NIAR) of Tangier, Morocco, to setting up SIT methods and contributing to Ceratitis control programs. The Monte Carlo method was used to simulate the concrete bunker in which the panoramic gamma irradiator is installed. To obtain a recommended DUR required for SIT programs, two cells similar of the Gammacell-220 irradiator, which is mainly used in the SIT programs around the world, were simulated inside the concrete bunker. The simulation and calculations were performed using the MCNPX-2.7e Monte Carlo simulation code. It is demonstrated that at both investigated positions, the spatial distribution of dose rates in the two modeled irradiation cells, which were similar to a gammacell-220 irradiator cell, are uniform enough that the cells can be used for SIT programs. It is concluded that the panoramic irradiator at NIAR can be used to contribute to the control of Mediterranean fly pest and other insect pests in Morocco.
Knowing and Controlling: Engineering Ideals and Gene Drive for Invasive Species Control in Aotearoa New Zealand
18025C. H. Ross, Nature Remade: Engineering Life, Envisioning Worlds, 2021-08-10 17:51:46.
On the islands of Aotearoa, also called New Zealand, invasive species have been a prominent and persistent concern for local ecosystems. Traditional methods of biological control, though, can be difficult to implement and often have harmful side- effects for the environment and human health. Recent developments in genetic engineering have led to the creation of a new technology called gene drive, which some have suggested may pro-vide a safer, easier alternative way to “restore damaged ecosystems and save endangered wildlife by genetically removing invasive species.” 1 While the promises of gene drive for invasive species control have attracted the attention of many in Aotearoa New Zealand interested in preserving or restoring the islands’ native environment, at the same time it has prompted calls for caution regarding their controllability and possible unintended consequences of their use. 2 However, the consideration of gene drive for the control of invasive species in Aotearoa New Zealand is more than just an issue of a controversial use of emerging biotechnology. At stake also are critical questions about what it means to know and control life. What are the kinds of knowledge that enable and underwrite the notions of controlling of life? If gene drive confers the power to control inva-sive species, who decides whether and how that control is exercised and with what responsibilities? And, crucially, what visions of the world are embedded in the aspirations of scientifically knowing and technologically controlling life?Controlling life has long been a central aspiration of the biological sciences. In the early twentieth century, aspirations to greater control over life manifested in rigorous laboratory experimentation, attempts to engineer organisms to be more amenable to human purposes, and explanatory commitments to a mechanistic conception of life. 3 Mechanistic approaches have been ubiquitous in biological practice aimed at bringing living things and their functions into the purview of human intention and volition by isolating, manipulating, and better understanding the function of more fundamental parts. 4 The widespread mechanistic approaches in biology
Analysis of the Segregation Distortion of FcRAN1 Genotypes Based on Whole-Genome Resequencing of Fig (Ficus carica L.) Breeding Parents
18171H. Ikegami, K. Shirasawa, H. Yakushiji, S. Yabe, M. Sato, T. Hayashi, K. Tashiro and H. Nogata, Frontiers in Plant Science, 12:8. 2021-08-10 14:56:28.
The common fig (Ficus carica L.) has a gynodioecious breeding system, and its sex phenotype is an important trait for breeding because only female plant fruits are edible. During breeding to select for female plants, we analyzed the FcRAN1 genotype, which is strongly associated with the sex phenotype. In 12 F-1 populations derived from 13 cross combinations, the FcRAN1 genotype segregation ratio was 1:1, whereas the M119226 x H238-107 hybridization resulted in an extremely male-biased segregation ratio (178:7 = male:female). This finding suggests that the segregation distortion was caused by some genetic factor(s). A whole-genome resequencing of breeding parents (paternal and maternal lines) identified 9,061 high-impact SNPs in the parents. A genome-wide linkage analysis exploring the gene(s) responsible for the distortion revealed 194 high-impact SNPs specific to Caprifig6085 (i.e., seed parent ancestor) and 215 high-impact SNPs specific to H238-107 (i.e., pollen parent) in 201 annotated genes. A comparison between the annotated genes and the genes required for normal embryo or gametophyte development and function identified several candidate genes possibly responsible for the segregation distortion. This is the first report describing segregation distortion in F. carica.
A common gene drive language eases regulatory process and eco-evolutionary extensions
18022P. Verma, R. G. Reeves and C. S. Gokhale, BMC Ecology and Evolution, 21:156. 2021-08-09 14:36:22.
Synthetic gene drive technologies aim to spread transgenic constructs into wild populations even when they impose organismal fitness disadvantages. The extraordinary diversity of plausible drive mechanisms and the range of selective parameters they may encounter makes it very difficult to convey their relative predicted properties, particularly where multiple approaches are combined. The sheer number of published manuscripts in this field, experimental and theoretical, the numerous techniques resulting in an explosion in the gene drive vocabulary hinder the regulators’ point of view. We address this concern by defining a simplified parameter based language of synthetic drives. Employing the classical population dynamics approach, we show that different drive construct (replacement) mechanisms can be condensed and evaluated on an equal footing even where they incorporate multiple replacement drives approaches. Using a common language, it is then possible to compare various model properties, a task desired by regulators and policymakers. The generalization allows us to extend the study of the invasion dynamics of replacement drives analytically and, in a spatial setting, the resilience of the released drive constructs. The derived framework is available as a standalone tool. Besides comparing available drive constructs, our tool is also useful for educational purpose. Users can also explore the evolutionary dynamics of future hypothetical combination drive scenarios. Thus, our results appraise the properties and robustness of drives and provide an intuitive and objective way for risk assessment, informing policies, and enhancing public engagement with proposed and future gene drive approaches.
Red queen’s race: rapid evolutionary dynamics of an expanding family of meiotic drive factors and their hpRNA suppressors
17957J. Vedanayagam, C.-J. Lin and E. C. Lai, bioRxiv, 2021.08.05.454923. 2021-08-06 16:51:10.
Meiotic drivers are a class of selfish genetic elements that are widespread across eukaryotes. Their activities are often detrimental to organismal fitness and thus trigger drive suppression to ensure fair segregation during meiosis. Accordingly, their existence is frequently hidden in genomes, and their molecular functions are little known. Here, we trace evolutionary steps that generated the Dox meiotic drive system in Drosophila simulans (Dsim), which distorts male:female balance (sex-ratio) by depleting male progeny. We show that Dox emerged via stepwise mobilization and acquisition of portions of multiple D. melanogaster genes, including the sperm chromatin packaging gene protamine. Moreover, we reveal novel Dox homologs in Dsim and massive, recent, amplification of Dox superfamily genes specifically on X chromosomes of its closest sister species D. mauritiana (Dmau) and D. sechellia (Dsech). The emergence of Dox superfamily genes is tightly associated with 1.688 family satellite repeats that flank de novo genomic copies. In concert, we find coordinated emergence and diversification of autosomal hairpin RNA/siRNAs loci that target subsets of Dox superfamily genes across simulans clade species. Finally, an independent set of protamine amplifications the Y chromosome of D. melanogaster indicates that protamine genes are frequent and recurrent players in sex chromosome dynamics. Overall, we reveal fierce genetic arms races between meiotic drive factors and siRNA suppressors associated with recent speciation.Competing Interest StatementThe authors have declared no competing interest.
Gene drives gaining speed
17972E. Bier, Nature Reviews Genetics, 2021-08-06 13:50:56.
Gene drives are selfish genetic elements that are transmitted to progeny at super-Mendelian (>50%) frequencies. Recently developed CRISPR–Cas9-based gene-drive systems are highly efficient in laboratory settings, offering the potential to reduce the prevalence of vector-borne diseases, crop pests and non-native invasive species. However, concerns have been raised regarding the potential unintended impacts of gene-drive systems. This Review summarizes the phenomenal progress in this field, focusing on optimal design features for full-drive elements (drives with linked Cas9 and guide RNA components) that either suppress target mosquito populations or modify them to prevent pathogen transmission, allelic drives for updating genetic elements, mitigating strategies including trans-complementing split-drives and genetic neutralizing elements, and the adaptation of drive technology to other organisms. These scientific advances, combined with ethical and social considerations, will facilitate the transparent and responsible advancement of these technologies towards field implementation.
The Promise of Genetics and Genomics for Improving Invasive Mammal Management on Islands
17936B. T. Burgess, R. L. Irvine, G. R. Howald and M. A. Russello, Frontiers in Ecology and Evolution, 9. 2021-08-03 13:21:15.
Invasive species are major contributors to global biodiversity decline. Invasive mammalian species (IMS), in particular, have profound negative effects in island systems that contain disproportionally high levels of species richness and endemism. The eradication and control of IMS have become important conservation tools for managing species invasions on islands, yet these management operations are often subject to failure due to knowledge gaps surrounding species- and system-specific characteristics, including invasion pathways and contemporary migration patterns. Here, we synthesize the literature on ways in which genetic and genomic tools have effectively informed IMS management on islands, specifically associated with the development and modification of biosecurity protocols, and the design and implementation of eradication and control programs. In spite of their demonstrated utility, we then explore the challenges that are preventing genetics and genomics from being implemented more frequently in IMS management operations from both academic and non-academic perspectives, and suggest possible solutions for breaking down these barriers. Finally, we discuss the potential application of genome editing to the future management of invasive species on islands, including the current state of the field and why islands may be effective targets for this emerging technology.
Invasive Mice and Engineered Genes
17952W. M. Adams and K. H. Redford, Yale University Press Blog, 2021-08-02 12:36:13.
On Gough Island, a steep speck of land deep in the South Atlantic, giant mice eat albatross chicks as they sit on their nests. They are house mice, accidental arrivals on the ships of long-dead sealers. But they have lost their secretive, timid, mousy ways. Over numerous generations, on an island without predators, they have become predators themselves. They have grown bigger, and fierce. The internet offers gruesome videos of Tristan albatross chicks being eaten alive in the night. The house mice of Gough Island are examples of one of the most serious and intractable drivers of biodiversity decline, invasive species. Not all species introduced by people outside their normal range become invasive, but invasive species are the most common threat to amphibians, reptiles, and mammals on the IUCN Red List, and have been a contributing cause in a quarter of plant extinctions and a third of animal extinctions in recent centuries. Traditional tools for addressing invasive species include traps, guns, fences, and particularly poisons. Though often effective, these often have undesired, and sometimes unexpected, knock-on effects on native species. Synthetic biology, the application of new genetic tools like CRISPR, is being explored as a source of new approaches to control with fewer side effects. The use of such methods in conservation blurs the distinction between what is natural and what is human-made.
2021 WHO guidelines on genetically modified mosquitoes
18084M. Makoni, The Lancet Microbe, 2:e353. 2021-08-01 17:27:59.
On May 19, 2021, WHO updated its guidelines for research and development on genetically modified mosquitoes, which define the standards for decision-making about how and when testing should proceed and describe best practices to ensure that research done in a public health context is safe, ethical, and rigorous. TDR, WHO's Special Programme for Research and Training in Tropical Diseases, and the GeneConvene Global Collaborative, an initiative of the Foundation for the National Institutes of Health, developed the updated guidelines building on the 2014 recommendations, integrating the latest advancements in mosquito genetic modification. “Vector-borne diseases are a major global public health issue. Over 100 countries are endemic for diseases such as dengue, malaria, and Zika. Dengue alone puts 2·5 billion people at risk”, says John Reeder (TDR and Department of Research for Health, WHO). Attacking the mosquitoes is an effective way of controlling the transmission of these diseases, but it is a massive task. “We are badly in need of new technologies that will change the game and allow effective, widespread control”, Reeder told The Lancet Microbe.
Host-associated differentiation of target pests should be assessed before using gene drive as a pest control tool – an opinion
17955R. F. Medina, Entomologia Experimentalis et Applicata, 2021-08-01 12:42:29.
Abstract Advances in gene editing have made feasible the potential use of gene drive for pest control. Ecological risk assessments will certainly be required before this technology can be released into open fields. In this article I argue for the importance to include host-associated differentiation (HAD) as part of ecological risk assessment models due to its potential to modulate gene drive spread and risk. Depending on context, HAD may hamper or facilitate pest control efforts using gene drives. Overlooking HAD may impair pest suppression goals and inflate estimations of effective population sizes whereas its inclusion within gene drive deployment strategies, as a form of ecological containment, may facilitate gene drive implementation under specific scenarios. Because HAD varies geographically and among closely related species, it will need to be assessed on a case-by-case basis. Failure to incorporate HAD within ecological risk assessment models may undermine pest control goals and diminish the accuracy of estimated ecological risks associated with gene drive releases.
Transgenic expression of Nix converts genetic females into males and allows automated sex sorting in Aedes albopictus
17888C. Lutrat, R. P. Olmo, T. Baldet, J. Bouyer and E. Marois, bioRxiv, 2021.07.28.454191. 2021-07-29 12:43:42.
Aedes albopictus is a major vector of arboviruses. Better understanding of its sex determination is crucial for developing mosquito control tools, especially genetic sexing strains. In Aedes aegypti, Nix is the primary gene responsible for masculinization and Nix-expressing genetic females develop into fertile, albeit flightless, males. In Ae. albopictus, Nix has also been implicated in masculinization but its role remains to be further characterized. In this work, we established Ae. albopictus transgenic lines ectopically expressing Nix. Several were composed exclusively of genetic females, with transgenic individuals being phenotypic and functional males due to the expression of the Nix transgene. Their reproductive fitness was marginally impaired, while their flight performance was similar to controls. Overall, our results show that Nix is sufficient for full masculinization in Ae. albopictus. Moreover, the transgene construct contains a fluorescence marker allowing efficient automated sex sorting. Consequently, such strains constitute valuable sexing strains for genetic control.Competing Interest StatementThe authors have declared no competing interest.
Horizontal Transmission of the Symbiont Microsporidia MB in Anopheles arabiensis
17856G. Nattoh, T. Maina, E. E. Makhulu, L. Mbaisi, E. Mararo, F. G. Otieno, T. Bukhari, T. O. Onchuru, E. Teal, J. Paredes, J. L. Bargul, D. M. Mburu, E. A. Onyango, G. Magoma, S. P. Sinkins and J. K. Herren, Frontiers in Microbiology, 12. 2021-07-28 13:43:29.
The recently discovered Anopheles symbiont, Microsporidia MB, has a strong malaria transmission-blocking phenotype in Anopheles arabiensis, the predominant Anopheles gambiae species complex member in many active transmission areas in eastern Africa. The ability of Microsporidia MB to block Plasmodium transmission together with vertical transmission and avirulence makes it a candidate for the development of a symbiont-based malaria transmission blocking strategy. We investigate the characteristics and efficiencies of Microsporidia MB transmission between An. arabiensis mosquitoes. We show that Microsporidia MB is not transmitted between larvae but is effectively transmitted horizontally between adult mosquitoes. Notably, Microsporidia MB was only found to be transmitted between male and female An. arabiensis, suggesting sexual horizontal transmission. In addition, Microsporidia MB cells were observed infecting the An. arabiensis ejaculatory duct. Female An. arabiensis that acquire Microsporidia MB horizontally are able to transmit the symbiont vertically to their offspring. We also investigate the possibility that Microsporidia MB can infect alternate hosts that live in the same habitats as their An. arabiensis hosts, but find no other non-anopheline hosts. Notably, Microsporidia MB infections were found in another primary malaria African vector, Anopheles funestus s.s. The finding that Microsporidia MB can be transmitted horizontally is relevant for the development of dissemination strategies to control malaria that are based on the targeted release of Microsporidia MB infected Anopheles mosquitoes.
Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field
17853A. Hammond, P. Pollegioni, T. Persampieri, A. North, R. Minuz, A. Trusso, A. Bucci, K. Kyrou, I. Morianou, A. Simoni, T. Nolan, R. Müller and A. Crisanti, Nature Communications, 12:4589. 2021-07-28 12:31:16.
CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings. Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.
Oxitec and MosquitoMate in the United States: lessons for the future of gene drive mosquito control
17890C. E. Schairer, J. Najera, A. A. James, O. S. Akbari and C. S. Bloss, Pathogens and Global Health, 2021-07-27 12:51:01.
ABSTRACTIn response to growing concerns regarding mosquito-borne diseases, scientists are developing novel systems of vector control. Early examples include Oxitec?s OX513A genetically-engineered mosquito and MosquitoMate?s Wolbachia-infected mosquito, and systems using ?gene-drive? are in development. Systems based on genetic engineering are controversial and institutions around the world are grappling with the question of who should have a say in how such technologies are field-tested and used. Based on media coverage and public records, we created comparative timelines of the efforts of Oxitec and MosquitoMate to navigate federal and local governance and bring their products to market in the United States. We analyze these timelines with particular attention to the role of public input in technology governance. These cases illustrate how governance of technology in the US is diverse, complex, and opaque. Further, the public response to proposed field trials of the Oxitec product highlights inconsistencies between public expectations for governance and actual practice. As gene-drive mosquito control products develop, both federal and local agencies will find their legitimacy tested without a better procedure for transparently integrating public input.
