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.
Meiotic defects in human oocytes: Potential causes and clinical implications
23677T. Wu, H. Gu, Y. Luo, L. Wang and Q. Sang, BioEssays, 2022-10-07 08:30:48.
Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error-prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), and clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models.
Wolbachia-Virus interactions and arbovirus control through population replacement in mosquitoes
23675T. H. Ant, M. V. Mancini, C. J. McNamara, S. M. Rainey and S. P. Sinkins, Pathogens and Global Health, 2022-10-07 08:27:10.
Following transfer into the primary arbovirus vector Aedes aegypti, several strains of the intracellular bacterium Wolbachia have been shown to inhibit the transmission of dengue, Zika, and chikungunya viruses, important human pathogens that cause significant morbidity and mortality worldwide. In addition to pathogen inhibition, many Wolbachia strains manipulate host reproduction, resulting in an invasive capacity of the bacterium in insect populations. This has led to the deployment of Wolbachia as a dengue control tool, and trials have reported significant reductions in transmission in release areas. Here, we discuss the possible mechanisms of Wolbachia-virus inhibition and the implications for long-term success of dengue control. We also consider the evidence presented in several reports that Wolbachia may cause an enhancement of replication of certain viruses under particular conditions, and conclude that these should not cause any concerns with respect to the application of Wolbachia to arbovirus control.
Fitness costs of Wolbachia shift in locally-adapted Aedes aegypti mosquitoes
23703P. A. Ross and A. A. Hoffmann, Environmental Microbiology, 2022-10-06 08:10:07.
Aedes aegypti mosquito eggs can remain quiescent for many months before hatching, allowing populations to persist through unfavorable conditions. Aedes aegypti infected with the Wolbachia strain wMel have been released in tropical and subtropical regions for dengue control. wMel reduces the viability of quiescent eggs, but this physiological cost might be expected to evolve in natural mosquito populations that frequently experience stressful conditions. We found that the cost of wMel infection differed consistently between mosquitoes collected from different locations and became weaker across laboratory generations, suggesting environment-specific adaptation of mosquitoes to the wMel infection. Reciprocal crossing experiments show that differences in the cost of wMel to quiescent egg viability were mainly due to mosquito genetic background and not Wolbachia origin. wMel-infected mosquitoes hatching from long-term quiescent eggs showed partial loss of cytoplasmic incompatibility and female infertility, highlighting additional costs of long-term quiescence. Our study provides the first evidence for a shift in Wolbachia phenotypic effects following deliberate field release and establishment and it highlights interactions between Wolbachia infections and mosquito genetic backgrounds. The unexpected changes in fitness costs observed here suggest potential tradeoffs with undescribed fitness benefits of the wMel infection.
Mitotic exchange in female germline stem cells is the major source of Sex Ratio chromosome recombination in Drosophila pseudoobscura
23719S. Koury, G3 Genes|Genomes|Genetics, 2022-10-04 06:48:20.
Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with three non-overlapping inversions. In the male germline, Sex Ratio chromosomes distort segregation of X and Y chromosomes (99:1), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (50:50), but non-overlapping inversions strongly suppress recombination establishing a 26 Megabase haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between non-overlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals these recombination events were at least 4-fold more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26 Megabase Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally-occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.
Aedes albopictus Sterile Male Production: Influence of Strains, Larval Diet and Mechanical Sexing Tools
M. Malfacini, A. Puggioli, F. Balestrino, M. Carrieri, M. L. Dindo and R. Bellini, Insects, 2022-10-03 08:08:09.The sterile insect technique (SIT) is a biologically based method of pest control, which relies on the mass production, sterilization, and release of sterile males of the target species. Since females can transmit viruses, it is important to develop a mass rearing system to produce a large number of males with a low presence of females. We evaluated the effects of different strains, larval diets and sexing tools on male productivity and residual female presence for the application of SIT against Aedes albopictus. Strains coming from Italy, Germany, Greece, and Montenegro, with different levels of colonization, were reared with three larval diets: IAEA-BY, BLP-B and SLP-BY. Developed pupae were sexed using two different mechanical methods: sieve or Fay-Morlan separator. The results proved that adoption of the Fay-Morlan separator increased the productivity and limited the female presence. The IAEA-BY diet showed the lowest female contamination. Strains with a high number of breeding generations showed a decreased productivity and an increased female presence. Increased female presence was found only in extensively reared strains and only when the sorting operation was conducted with sieves. We hypothesize that extensive colonization may determine a size reduction which limits the sexing tool efficiency itself.
Justifying an Intentional Species Extinction: The Case of Anopheles gambiae
23662D. E. Callies and Y. Rohwer, Environmental Values, 31:193-210. 2022-10-01 06:16:34.
Each year, over 200 million people are infected with the malaria parasite, nearly half a million of whom succumb to the disease. Emerging genetic technologies could, in theory, eliminate the burden of malaria throughout the world by intentionally eradicating the mosquitoes that transmit the disease. In this paper, we offer an ethical examination of the intentional eradication of Anopheles gambiae, the main malaria vector of sub-Saharan Africa. In our evaluation, we focus on two main considerations: the benefit of alleviating the malaria burden, and the loss of value that would accompany the eradication of the species. We outline a typology of the different ways in which species are valued or could be valuable, then use that typology to appraise the value of the species in question. We argue that Anopheles gambiae has minor (and redundant) instrumental value, little final subjective value and no objective final value.
Distribution of sex ratio distorters in natural populations of the isopod Armadillidium vulgare
236442022-09-30 08:15:09.
Externalities modulate the effectiveness of the Wolbachia release programme
23611E. E. Ooi and A. Wilder-Smith, The Lancet Infectious Diseases, 2022-09-28 09:16:47.
Despite the remarkable outcome in Yogyakarta, the wMel approach also has some challenges. In particular, the extent to which ecological, weather, and other external factors influence the dissemination and establishment of wMel in complex urban environments remains unclear. Whether the high and sustained penetration rate of wMel and the efficacy in preventing dengue that was observed in Yogyakarta are readily reproducible in other regions of the world that are vulnerable to repeated outbreaks of such viral diseases is also unclear. We therefore welcome the study into the real-world effectiveness of large-scale wMel release in the urban setting of Rio de Janeiro.3 The study assessed the rate of wMel introgression at the neighbourhood level and its effect on the localised incidence of dengue and chikungunya. Mosquitoes were released over a 2·5-year period starting in August, 2017.
Estimating the effect of the wMel release programme on the incidence of dengue and chikungunya in Rio de Janeiro, Brazil: a spatiotemporal modelling study
23608G. Ribeiro dos Santos, B. Durovni, V. Saraceni, T. I. Souza Riback, S. B. Pinto, K. L. Anders, et al., The Lancet Infectious Diseases, 2022-09-28 09:07:02.
Summary Background Introgression of genetic material from species of the insect bacteria Wolbachia into populations of Aedes aegypti mosquitoes has been shown in randomised and non-randomised trials to reduce the incidence of dengue; however, evidence for the real-world effectiveness of large-scale deployments of Wolbachia-infected mosquitoes for arboviral disease control in endemic settings is still scarce. A large Wolbachia (wMel strain) release programme was implemented in 2017 in Rio de Janeiro, Brazil. We aimed to assess the effect of this programme on the incidence of dengue and chikungunya in the city. Methods 67 million wMel-infected mosquitoes were released across 28 489 locations over an area of 86·8 km2 in Rio de Janeiro between Aug 29, 2017 and Dec 27, 2019. Following releases, mosquitoes were trapped and the presence of wMel was recorded. In this spatiotemporal modelling study, we assessed the effect of the release programme on the incidence of dengue and chikungunya. We used spatiotemporally explicit mathematical models applied to geocoded dengue cases (N=283 270) from 2010 to 2019 and chikungunya cases (N=57 705) from 2016 to 2019. Findings On average, 32% of mosquitoes collected from the release zones between 1 month and 29 months after the initial release tested positive for wMel. Reduced wMel introgression occurred in locations and seasonal periods in which cases of dengue and chikungunya were historically high, with a decrease to 25% of mosquitoes testing positive for wMel during months in which disease incidence was at its highest. Despite incomplete introgression, we found that the releases were associated with a 38% (95% CI 32–44) reduction in the incidence of dengue and a 10% (4–16) reduction in the incidence of chikungunya. Interpretation Stable establishment of wMel in the geographically diverse, urban setting of Rio de Janeiro seems to be more complicated than has been observed elsewhere. However, even intermediate levels of wMel seem to reduce the incidence of disease caused by two arboviruses. These findings will help to guide future release programmes. Funding Bill & Melinda Gates Foundation and the European Research Council.
The Involvement of Atlastin in Dengue Virus and Wolbachia Infection in Aedes aegypti and Its Regulation by aae-miR-989
23637M. Hussain, T. Bradshaw, M. Lee and S. Asgari, Microbiology Spectrum, 2022-09-27 06:48:46.
Endoplasmic reticulum (ER)-shaping atlastin proteins (ATLs) have been demonstrated to play a functional role during flavivirus replication in mammalian cells. For dengue virus (DENV), atlastin is required in the formation of the replication organelles and RNA replication, virion assembly, production of the infectious virus particles, and trafficking or directing the association of vesicle packets with furin. Here, we investigated the involvement of atlastin in DENV replication in the mosquito Aedes aegypti and explored the possibility of its manipulation by the endosymbiotic bacterium Wolbachia to interfere with DENV replication. Results showed the expression of Ae. aegypti atlastin gene (AaATL) was upregulated in DENV-infected Aag2 cells, and its silencing led to reduced DENV replication. Contrary to our assumption that AaATL could be downregulated by Wolbachia, we did not find evidence for that in Wolbachia-infected cell lines, but this was the case in mosquitoes. Further, silencing AaATL did not have any effect on Wolbachia density. Our results also suggest that aae-miR-989 miRNA negatively regulates AaATL. The oversupply of the miRNA mimic led to reduced DENV replication consistent with the positive role of AaATL in DENV replication. Overall, the results favor AaATL’s involvement in DENV replication; however, there is no support that the protein is involved in Wolbachia-mediated DENV inhibition. In addition, the results contribute to discerning further possible overlapping functions of ATLs in mosquitoes and mammalian cells.
Wolbachia action in the sperm produces developmentally deferred chromosome segregation defects during the Drosophila mid-blastula transition
23615B. Warecki, S. W. A. Titen, M. S. Alam, G. Vega, N. Lemseffer, K. Hug, et al., eLife, 11:e81292. 2022-09-23 09:36:01.
Wolbachia, a vertically transmitted endosymbiont infecting many insects, spreads rapidly through uninfected populations by a mechanism known as cytoplasmic incompatibility (CI). In CI, a paternally delivered modification of the sperm leads to chromatin defects and lethality during and after the first mitosis of embryonic development in multiple species. However, whether CI-induced defects in later stage embryos are a consequence of the first division errors or caused by independent defects remains unresolved. To address this question, we focused on ~1/3 of embryos from CI crosses in Drosophila simulans that develop apparently normally through the first and subsequent pre-blastoderm divisions before exhibiting mitotic errors during the mid-blastula transition and gastrulation. We performed single embryo PCR and whole genome sequencing to find a large percentage of these developed CI-derived embryos bypass the first division defect. Using fluorescence in situ hybridization, we find increased chromosome segregation errors in gastrulating CI-derived embryos that had avoided the first division defect. Thus, Wolbachia action in the sperm induces developmentally deferred defects that are not a consequence of the first division errors. Like the immediate defect, the delayed defect is rescued through crosses to infected females. These studies inform current models on the molecular and cellular basis of CI.
Meiotic drive is associated with sexual incompatibility in Neurospora
23613A. Vogan, J. Svedberg, M. Grudzinska-Sterno and H. Johannesson, Evolution, 2022-09-23 09:26:32.
Evolution of Bateson-Dobzhansky-Muller (BDM) incompatibilities is thought to represent a key step in the formation of separate species. They are incompatible alleles that have evolved in separate populations and are exposed in hybrid offspring as hybrid sterility or lethality. In this study we reveal a previously unconsidered mechanism promoting the formation of BDM incompatibilities, meiotic drive. Theoretical studies have evaluated the role that meiotic drive, the phenomenon whereby selfish elements bias their transmission to progeny at ratios above 50:50, plays in speciation, and have mostly concluded that drive could not result in speciation on its own. Using the model fungus Neurospora, we demonstrate that the large meiotic drive haplotypes, Sk-2 and Sk-3, contain putative sexual incompatibilities. Our experiments revealed that while crosses between N. intermedia and N. metzenbergii produce viable progeny at appreciable rates, when strains of N. intermedia carry Sk-2 or Sk-3 the proportion of viable progeny drops substantially. Additionally, it appears that Sk-2 and Sk-3 have accumulated different incompatibility phenotypes, consistent with their independent evolutionary history. This research illustrates how meiotic drive can contribute to reproductive isolation between populations, and thereby speciation. This article is protected by copyright. All rights reserved.
Fitness effects of CRISPR endonucleases in Drosophila melanogaster populations
23673A. M. Langmüller, J. Champer, S. Lapinska, L. Xie, M. Metzloff, S. E. Champer, J. Liu, Y. Xu, J. Du, A. G. Clark and P. W. Messer, eLife, 11:e71809. 2022-09-22 08:22:04.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 provides a highly efficient and flexible genome editing technology with numerous potential applications ranging from gene therapy to population control. Some proposed applications involve the integration of CRISPR/Cas9 endonucleases into an organism’s genome, which raises questions about potentially harmful effects to the transgenic individuals. One example for which this is particularly relevant are CRISPR-based gene drives conceived for the genetic alteration of entire populations. The performance of such drives can strongly depend on fitness costs experienced by drive carriers, yet relatively little is known about the magnitude and causes of these costs. Here, we assess the fitness effects of genomic CRISPR/Cas9 expression in Drosophila melanogaster cage populations by tracking allele frequencies of four different transgenic constructs that allow us to disentangle ‘direct’ fitness costs due to the integration, expression, and target-site activity of Cas9, from fitness costs due to potential off-target cleavage. Using a maximum likelihood framework, we find that a model with no direct fitness costs but moderate costs due to off-target effects fits our cage data best. Consistent with this, we do not observe fitness costs for a construct with Cas9HF1, a high-fidelity version of Cas9. We further demonstrate that using Cas9HF1 instead of standard Cas9 in a homing drive achieves similar drive conversion efficiency. These results suggest that gene drives should be designed with high-fidelity endonucleases and may have implications for other applications that involve genomic integration of CRISPR endonucleases.
Wolbachia strain wAlbB remains stable in Aedes aegypti over 15 years but exhibits genetic background-dependent variation in virus blocking
23646X. Liang, C. H. Tan, Q. Sun, M. Zhang, P. J. Wong, M. I. Li, et al., PNAS Nexus, 2022-09-22 08:20:54.
The ability of the maternally transmitted endosymbiotic bacterium Wolbachia to induce cytoplasmic incompatibility (CI) and virus blocking makes it a promising weapon for combatting mosquito-borne diseases through either suppression or replacement of wild-type populations. Recent field trials show that both approaches significantly reduce the incidence of dengue fever in humans. However, new questions emerge about how Wolbachia-mosquito associations will co-evolve over time and whether Wolbachia-mediated virus blocking will be affected by the genetic diversity of mosquitoes and arboviruses in the real world. Here, we have compared the Wolbachia density and CI expression of two wAlbB-infected Aedes aegypti lines transinfected 15 years apart. We have also assessed wAlbB-mediated virus blocking against dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) viruses and examined whether host genetic backgrounds modulate viral blocking effects by comparing ZIKV infection in mosquitoes with a Mexican genetic background to those with a Singaporean background. Our results show that over 15 years, wAlbB maintained the capacity to form a stable association with Ae. aegypti in terms of both density and CI expression. There were variations in wAlbB-induced virus blocking against CHIKV, DENV, and ZIKV, and higher inhibitory effects on ZIKV in mosquitoes on the Singaporean genetic background than on the Mexican background. These results provide important information concerning the robustness and long-term stability of Wolbachia as a biocontrol agent for arbovirus disease control.
Daisy-chain gene drives: The role of low cut-rate, resistance mutations, and maternal deposition
23623S. A. N. Verkuijl, M. A. E. Anderson, L. Alphey and M. B. Bonsall, PLOS Genetics, 18:e1010370. 2022-09-19 14:37:34.
Author summary Reducing the harm of pest species by the introgression of traits into a wild population is often limited by the difficulties of mass rearing and release of modified individuals. Gene drives present an opportunity to substantially reduce the release frequencies required to spread a particular modification. However, uniform modification of a target species is, with a few specific exceptions, not necessary or desirable. Self-limiting gene drives, such as daisy-chain gene drives, have been widely discussed as a potential solution, allowing the invasiveness of a drive release to be tuned to the target population. Here, we investigate through computational modelling how daisy-chain gene drives perform when subjected to commonly observed inefficiencies associated with CRISPR-Cas9-based inheritance biasing. Compared to a self-perpetuating drive, daisy-chain gene drives are sensitive to factors that cause their separate elements to segregate prematurely. In particular, a reduction in the DNA cut-rate and an increase in the formation of resistance alleles. We find that the effect of inefficiencies in the drive mechanism is generally more pronounced when the drive is at low frequencies. With low rates of migration, this substantially reduces daisy-chain gene drives spread into a neighbouring non-target population.
Genome sequencing and comparative analysis of Wolbachia strain wAlbA reveals Wolbachia-associated plasmids are common
23606J. Martinez, T. H. Ant, S. M. Murdochy, L. Tong, A. da Silva Filipe and S. P. Sinkins, PLOS Genetics, 18:e1010406. 2022-09-19 05:21:48.
Wolbachia is the most common bacterial symbiont of arthropods, being found in about half of terrestrial species around the globe. It is transmitted from mother to offspring, can spread rapidly by inducing various forms of reproductive parasitism and often provides protection against viral pathogens. These properties are being harnessed by disease control interventions introducing Wolbachia into wild populations of virus-transmitting mosquitoes. Here we sequenced the genome of wAlbA, a strain of the symbiont naturally found in Aedes albopictus mosquitoes and demonstrate that it is associated with two extrachromosomal plasmid elements. We then reanalysed publicly available sequencing data and found that plasmids are much more common in Wolbachia than previously thought. Some of them carry genes potentially important for symbiosis and reproductive manipulation as well as phage-like genes that may allow them to move between symbiont strains. Our findings provide a new framework for studying Wolbachia and will help the future development of genetic tools for manipulating symbiont genomes.
Meiotic drive does not impede success in sperm competition in the stalk-eyed fly, Teleopsis dalmanni
23566S. Bates, L. Meade and A. Pomiankowski, bioRxiv, 2022-09-13 15:00:24.
Meiotic drive genes are selfish genetic elements that distort Mendelian patterns of inheritance to bias transmission in their favour. We use the stalk-eyed fly, Teleopsis dalmanni, to investigate the fitness effects associated with a meiotic drive gene called Sex Ratio (SR), which is linked to the X chromosome. In males, SR destroys Y-bearing sperm, meaning only X-bearing sperm are viable, and females who mate with drive males sire all-female broods. This confers a two-fold transmission advantage to the SR gene, as it is transmitted to all offspring.We recently discovered that drive males have evolved compensatory mechanisms to cope with the sperm destruction caused by meiotic drive. They have greatly enlarged testes, allowing them to produce more sperm. When drive males mate with females, they deliver as many sperm and sire as many offspring as wildtype males. Building on this finding, we measured how drive male sperm performs against sperm from a non-carrier male in sperm competition – where the sperm from different males compete to fertilise an egg. Double mating trials were performed, where a single female was mated once to a drive and once to a non-carrier male. By genotyping offspring, we show that the number of offspring sired by the drive male was not different from the number sired by the non-carrier competitor.These findings contrast with those in other species. Typically, drive males do poorly in sperm competition and their spread is severely restricted by sperm competition. In stalk-eyed flies, female multiple mating with many males is the norm, but this does not appear to inhibit the fertility of drive males. The success of drive under sperm competition helps to explain the high frequency of drive around 20% in natural populations of T. dalmanni.Competing Interest StatementThe authors have declared no competing interest.
Enforcement of Postzygotic Species Boundaries in the Fungal Kingdom
23560J. Y. Chou, P. C. Hsu and J. Y. Leu, Microbiology and Molecular Biology Reviews, 2022-09-13 14:48:04.
Understanding the molecular basis of speciation is a primary goal in evolutionary biology. The formation of the postzygotic reproductive isolation that causes hybrid dysfunction, thereby reducing gene flow between diverging populations, is crucial for speciation. Using various advanced approaches, including chromosome replacement, hybrid introgression and transcriptomics, population genomics, and experimental evolution, scientists have revealed multiple mechanisms involved in postzygotic barriers in the fungal kingdom. These results illuminate both unique and general features of fungal speciation. Our review summarizes experiments on fungi exploring how Dobzhansky-Muller incompatibility, killer meiotic drive, chromosome rearrangements, and antirecombination contribute to postzygotic reproductive isolation. We also discuss possible evolutionary forces underlying different reproductive isolation mechanisms and the potential roles of the evolutionary arms race under the Red Queen hypothesis and epigenetic divergence in speciation.
Quality control traceability during the packing and release process of Ceratitis capitata for sterile insect technique
23621Y. Contreras-Navarro, H. Luis-Alvarez, G. García-Coapio, R. Hernández, S. Flores and P. Montoya, Journal of Applied Entomology, 2022-09-13 14:29:43.
Abstract In programmes applying the sterile insect technique (SIT), the quality of insects deployed in the field determines the success in preventing, suppressing, containing or eradicating the pest population. In the fruit fly emergence and release facility (ERF) of the Moscamed Program in Mexico, irradiated pupae of Ceratitis capitata are packed in Mexico-type towers, and key adult quality parameters, such as emergence, fliers and survival, are determined throughout the packing, handling and release process. However, different methodologies are used to estimate the percentage of fliers in the different stages of the process, raising doubts of whether observed differences are due to the effect of each stage or to the methodology used. With this in mind, we developed an alternative called ?Adult Flier device? (=AF-device) to evaluate the adult flier parameter following a critical evaluation path of five steps: (1) upon arrival at ERF, (2) post-packing, (3) post-holding, (4) post-chilling and (5) post-release, where adult fliers and survival under stress were evaluated. We also compared the current methodologies for the estimation of ?absolute fliers? available in different operating manuals. Our results suggest that the AF-device allows reliable traceability of sterile insect quality parameters throughout the packing and release process, since no significant differences were observed with the control treatments. In the chilling stage, the five methodologies tested were equivalent, but the AF-device was less time-consuming and required less manpower and biological material than the other methodological options. Our results demonstrate that the use of the AF-device can be a feasible, versatile, innovative and efficient alternative to evaluate quality control parameters throughout the process of packing and releasing sterile insects, providing reliable results in a timely manner with less hand labour using minimal biological material.
Transposable elements
A. Hayward and C. Gilbert, Current Biology, 32:R904-r909. 2022-09-12 14:43:26.Transposable elements are known by many names, including 'transposons', 'interspersed repeats', 'selfish genetic elements', 'jumping genes', and 'parasitic DNA', but here we will refer to them simply as transposable elements. Many biologists will have heard of transposable elements and their ability to transpose (change position) within the genome. But fewer may be aware of their varied influences on host biology, including contributions to the evolution of diverse host traits such as internal gestation, memory, colouration, and adaptive immunity. Transposable elements are a near ubiquitous feature of eukaryotic genomes, and they often comprise a substantial proportion of total genomic content. Consequently, transposable element genes are considered among the most abundant coding sequences in nature. Recent advances in genome sequencing have ushered in a golden age for transposable-element research, providing opportunities to greatly improve our understanding of the effects of transposable elements on host evolution and disease. However, our ability to detect and analyse transposable elements still faces significant challenges, impairing efforts to decipher their evolution, characterise their diversity, and elucidate their myriad host influences. Below, we summarise key aspects of transposable element biology in eukaryotes and discuss major outstanding research questions.
Selfish evolution of placental hormones
23534G. Keegan and M. M. Patten, Evolution, Medicine, and Public Health, 10:391-397. 2022-09-10 05:50:19.
We hypothesize that some placental hormones—specifically those that arise by tandem duplication of genes for maternal hormones—may behave as gestational drivers, selfish genetic elements that encourage the spontaneous abortion of offspring that fail to inherit them. Such drivers are quite simple to evolve, requiring just three things: a decrease in expression or activity of some essential maternal hormone during pregnancy; a compensatory increase in expression or activity of the homologous hormone by the placenta; and genetic linkage between the two effects. Gestational drive may therefore be a common selection pressure experienced by any of the various hormones of mammalian pregnancy that have arisen by tandem gene duplication. We examine the evolution of chorionic gonadotropin in the human lineage in light of this hypothesis. Finally, we postulate that some of the difficulties of human pregnancy may be a consequence of the action of selfish genes.We show how placental hormones that have arisen via tandem gene duplication from maternally produced hormones may subsequently experience selection as selfish genetic elements and spread through populations despite causing reproductive inefficiency. We examine the implications of this hypothesis and point to some empirical tests.
Analysis of Aedes aegypti microRNAs in response to Wolbachia wAlbB infection and their potential role in mosquito longevity
23564C. Bishop, M. Hussain, L. E. Hugo and S. Asgari, Scientific Reports, 12:15245. 2022-09-09 14:56:37.
The mosquito Aedes aegypti is the primary vector of a range of medically important viruses including dengue, Zika, West Nile, yellow fever, and chikungunya viruses. The endosymbiotic bacterium Wolbachia pipientis wAlbB strain is a promising biocontrol agent for blocking viral transmission by Ae. aegypti. To predict the long-term efficacy of field applications, a thorough understanding of the interactions between symbiont, host, and pathogen is required. Wolbachia influences host physiology in a variety of ways including reproduction, immunity, metabolism, and longevity. MicroRNAs (miRNAs) are highly conserved small non-coding RNAs that regulate gene expression in eukaryotes and viruses. Several miRNAs are known to regulate biological processes in Drosophila and mosquitoes, including facilitating Wolbachia maintenance. We generated the first chromosomal map of Ae. aegypti miRNAs, and compared miRNA expression profiles between a wAlbB-transinfected Ae. aegypti mosquito line and a tetracycline cleared derivative, using deep small RNA-sequencing. We found limited modulation of miRNAs in response to wAlbB infection. Several miRNAs were modulated in response to age, some of which showed greater upregulation in wAlbB-infected mosquitoes than in tetracycline cleared ones. By selectively inhibiting some differentially expressed miRNAs, we identified miR-2946-3p and miR-317-3p as effecting mosquito longevity in Wolbachia-infected mosquitoes.
A detailed landscape of CRISPR-Cas-mediated plant disease and pest management
23532S. Karmakar, P. Das, D. Panda, K. Xie, M. J. Baig and K. A. Molla, Plant Science, 323:111376. 2022-09-09 05:44:18.
Genome editing technology has rapidly evolved to knock-out genes, create targeted genetic variation, install precise insertion/deletion and single nucleotide changes, and perform large-scale alteration. The flexible and multipurpose editing technologies have started playing a substantial role in the field of plant disease management. CRISPR-Cas has reduced many limitations of earlier technologies and emerged as a versatile toolbox for genome manipulation. This review summarizes the phenomenal progress of the use of the CRISPR toolkit in the field of plant pathology. CRISPR-Cas toolbox aids in the basic studies on host-pathogen interaction, in identifying virulence genes in pathogens, deciphering resistance and susceptibility factors in host plants, and engineering host genome for developing resistance. We extensively reviewed the successful genome editing applications for host plant resistance against a wide range of biotic factors, including viruses, fungi, oomycetes, bacteria, nematodes, insect pests, and parasitic plants. Recent use of CRISPR-Cas gene drive to suppress the population of pathogens and pests has also been discussed. Furthermore, we highlight exciting new uses of the CRISPR-Cas system as diagnostic tools, which rapidly detect pathogenic microorganism. This comprehensive yet concise review discusses innumerable strategies to reduce the burden of crop protection.
On the Mechanistic Basis of Killer Meiotic Drive in Fungi
23530S. J. Saupe and H. Johannesson, Annual Review of Microbiology, 76:305-323. 2022-09-08 05:38:51.
Spore killers are specific genetic elements in fungi that kill sexual spores that do not contain them. A range of studies in the last few years have provided the long-awaited first insights into the molecular mechanistic aspects of spore killing in different fungal models, including both yeast-forming and filamentous Ascomycota. Here we describe these recent advances, focusing on the wtf system in the fission yeast Schizosaccharomyces pombe; the Sk spore killers of Neurospora species; and two spore-killer systems in Podospora anserina, Spok and [Het-s]. The spore killers appear thus far mechanistically unrelated. They can involve large genomic rearrangements but most often rely on the action of just a single gene. Data gathered so far show that the protein domains involved in the killing and resistance processes differ among the systems and are not homologous. The emerging picture sketched by these studies is thus one of great mechanistic and evolutionary diversity of elements that cheat during meiosis and are thereby preferentially inherited over sexual generations.
Life-history traits of a fluorescent Anopheles arabiensis genetic sexing strain introgressed into South African genomic background
23550N. L. Ntoyi, T. Mashatola, J. Bouyer, C. Kraupa, H. Maiga, W. Mamai, N. S. Bimbile-Somda, T. Wallner, D. O. Carvalho, G. Munhenga and H. Yamada, Malaria Journal, 21:12. 2022-09-05 06:11:50.
Background South Africa has set a mandate to eliminate local malaria transmission by 2023. In pursuit of this objective a Sterile Insect Technique programme targeting the main vector Anopheles arabiensis is currently under development. Significant progress has been made towards operationalizing the technology. However, one of the main limitations being faced is the absence of an efficient genetic sexing system. This study is an assessment of an An. arabiensis (AY-2) strain carrying the full Y chromosome from Anopheles gambiae, including a transgenic red fluorescent marker, being introgressed into a South African genetic background as a potential tool for a reliable sexing system. Methods Adult, virgin males from the An. arabiensis AY-2 strain were outcrossed to virgin females from the South African, Kwazulu-Natal An. arabiensis (KWAG strain) over three generations. Anopheles arabiensis AY-2 fluorescent males were sorted as first instar larvae (L1) using the Complex Object Parametric Analyzer and Sorter (COPAS) and later screened as pupae to verify the sex. Life history traits of the novel hybrid KWAG-AY2 strain were compared to the original fluorescent AY-2 strain, the South African wild-type KWAG strain and a standard laboratory An. arabiensis (Dongola reference strain). Results The genetic stability of the sex-linked fluorescent marker and the integrity and high level of sexing efficiency of the system were confirmed. No recombination events in respect to the fluorescent marker were detected over three rounds of introgression crosses. KWAG-AY2 had higher hatch rates and survival of L1 to pupae and L1 to adult than the founding strains. AY-2 showed faster development time of immature stages and larger adult body size, but lower larval survival rates. Adult KWAG males had significantly higher survival rates. There was no significant difference between the strains in fecundity and proportion of males. KWAG-AY2 males performed better than reference strains in flight ability tests. Conclusion The life history traits of KWAG-AY2, its rearing efficiency under laboratory conditions, the preservation of the sex-linked fluorescence and perfect sexing efficiency after three rounds of introgression crosses, indicate that it has potential for mass rearing. The potential risks and benefits associated to the use of this strain within the Sterile Insect Technique programme in South Africa are discussed.
Toward product-based regulation of crops
23498F. Gould, R. M. Amasino, D. Brossard, C. R. Buell, R. A. Dixon, J. B. Falck-Zepeda, M. A. Gallo, K. E. Giller, L. L. Glenna, T. Griffin, D. Magraw, C. Mallory-Smith, K. V. Pixley, E. P. Ransom, D. M. Stelly and C. N. Stewart, Science, 377:1051-1053. 2022-09-02 19:04:01.
Current process-based approaches to regulation are no longer fit for purpose Much effort has been expended globally over the past four decades to craft and update country-specific and multinational safety regulations that can be applied to crops developed by genetic engineering processes, while exempting conventionally bred crops. This differentiation made some sense in the 1980s, but in light of technological advances, it is no longer scientifically defensible. In the coming decades, innovations in genetic engineering and modern ?conventional? processes of crop development will enable use of these approaches to alter more crops and more traits. Future governance of new plant varieties and foods, regardless of the processes and techniques used to develop them, will require new, scientifically sound assessment methodologies, developed in a manner acceptable to society. Here, we provide a rationale for one governance approach that moves away from current process-based regulation and uses newly developed molecular techniques that enable detailed characterization of the new crops and foods themselves.
An optimal control problem for dengue transmission model with Wolbachia and vaccination
23694J. Zhang, L. L. Liu, Y. Z. Li and Y. Wang, Communications In Nonlinear Science and Numerical Simulation, 116. 2022-09-02 07:47:59.
The release of Wolbachia-infected mosquitoes into the wild mosquitoes population is an excellent biological control strategy which can be effective against mosquito-borne infections. In this work, we propose a dengue transmission model that incorporates releasing Wolbachia into the wild mosquito population and vaccinating human population. We analyze the basic reproduction number, the existence and stability of the equilibria, and carry out the sensitivity analysis to quantify the effects of parameters on the basic reproduction number. The analysis shows that the basic reproduction number determines the stability of two equilibria, and two transmission probabilities are positively correlated with the basic reproduction number, especially, the transmission probability of human being infected byWolbachia-infected mosquitoes is more sensitive than that of wild mosquitoes. Based on an integrated control strategy for the prevention of dengue fever (vaccination, using mosquito nets, improved treatment of dengue and spraying insecticides), we derive the necessary conditions for the optimal control problem using Pontryagin's Maximum Principle and carry out numerical simulations by MATLAB. Finally, the cost-effectiveness analysis of several control strategies is examined to determine the most feasible strategy. It shows that the most cost-effective integrated strategy is vaccination, using mosquito nets and spraying insecticides. (c) 2022 Elsevier B.V. All rights reserved.
An evaluation of fusion partner proteins for paratransgenesis in Asaia bogorensis
24274C. Grogan, M. Bennett and D. J. Lampe, Plos One, 17:18. 2022-09-01 14:11:14.
Mosquitoes transmit many pathogens responsible for human diseases, such as malaria which is caused by parasites in the genus Plasmodium. Current strategies to control vector-transmitted diseases are increasingly undermined by mosquito and pathogen resistance, so additional methods of control are required. Paratransgenesis is a method whereby symbiotic bacteria are genetically modified to affect the mosquito's phenotype by engineering them to deliver effector molecules into the midgut to kill parasites. One paratransgenesis candidate is Asaia bogorensis, a Gram-negative bacterium colonizing the midgut, ovaries, and salivary glands of Anopheles sp. mosquitoes. Previously, engineered Asaia strains using native signals to drive the release of the antimicrobial peptide, scorpine, fused to alkaline phosphatase were successful in significantly suppressing the number of oocysts formed after a blood meal containing P. berghei. However, these strains saw high fitness costs associated with the production of the recombinant protein. Here, we report evaluation of five different partner proteins fused to scorpine that were evaluated for effects on the growth and fitness of the transgenic bacteria. Three of the new partner proteins resulted in significant levels of protein released from the Asaia bacterium while also significantly reducing the prevalence of mosquitoes infected with P. berghei. Two partners performed as well as the previously tested Asaia strain that used alkaline phosphatase in the fitness analyses, but neither exceeded it. It may be that there is a maximum level of fitness and parasite inhibition that can be achieved with scorpine being driven constitutively, and that use of a Plasmodium specific effector molecule in place of scorpine would help to mitigate the stress on the symbionts.
Bacterial supergroup-specific “cost” of Wolbachia infections in Nasonia vitripennis
23640A. Tiwary, R. Babu, R. Sen and R. Raychoudhury, Ecology and Evolution, 2022-09-01 08:00:24.
Abstract The maternally inherited endosymbiont, Wolbachia, is known to alter the reproductive biology of its arthropod hosts for its own benefit and can induce both positive and negative fitness effects in many hosts. Here, we describe the effects of the maintenance of two distinct Wolbachia infections, one each from supergroups A and B, on the parasitoid host Nasonia vitripennis. We compare the effect of Wolbachia infections on various traits between the uninfected, single A-infected, single B-infected, and double-infected lines with their cured versions. Contrary to some previous reports, our results suggest that there is a significant cost associated with the maintenance of Wolbachia infections where traits such as family size, fecundity, longevity, and rates of male copulation are compromised in Wolbachia-infected lines. The double Wolbachia infection has the most detrimental impact on the host as compared to single infections. Moreover, there is a supergroup-specific negative impact on these wasps as the supergroup B infection elicits the most pronounced negative effects. These negative effects can be attributed to a higher Wolbachia titer seen in the double and the single supergroup B infection lines when compared to supergroup A. Our findings raise important questions on the mechanism of survival and maintenance of these reproductive parasites in arthropod hosts.
Applications of gene drive systems for population suppression of insect pests
23503M. Asad, D. Liu, J. Chen and G. Yang, Bulletin of Entomological Research, 2022-08-31 19:19:28.
Population suppression is an effective way for controlling insect pests and disease vectors, which cause significant damage to crop and spread contagious diseases to plants, animals and humans. Gene drive systems provide innovative opportunities for the insect pests population suppression by driving genes that impart fitness costs on populations of pests or disease vectors. Different gene-drive systems have been developed in insects and applied for their population suppression. Here, different categories of gene drives such as meiotic drive (MD), under-dominance (UD), homing endonuclease-based gene drive (HEGD) and especially the CRISPR/Cas9-based gene drive (CCGD) were reviewed, including the history, types, process and mechanisms. Furthermore, the advantages and limitations of applying different gene-drive systems to suppress the insect population were also summarized. This review provides a foundation for developing a specific gene-drive system for insect population suppression.
A confinable female-lethal population suppression system in the malaria vector, Anopheles gambiae
23500A. L. Smidler, J. J. Pai, R. A. Apte, H. M. Sánchez C, R. M. Corder, E. J. Gutiérrez, N. Thakre, I. Antoshechkin, J. M. Marshall and O. S. Akbari, bioRxiv, 2022.08.30.505861. 2022-08-30 19:10:47.
Malaria is among the world’s deadliest diseases, predominantly affecting sub-Saharan Africa, and killing over half a million people annually. Controlling the principal vector, the mosquito Anopheles gambiae, as well as other anophelines, is among the most effective methods to control disease spread. Here we develop an innovative genetic population suppression system termed Ifegenia (Inherited Female Elimination by Genetically Encoded Nucleases to Interrupt Alleles) in this deadly vector. In this bicomponent CRISPR-based approach, we disrupt a female-essential gene, femaleless (fle), demonstrating complete genetic sexing via heritable daughter gynecide. Moreover, we show that Ifegenia males remain reproductively viable, and can load both fle mutations and CRISPR machinery to induce fle mutations in subsequent generations, resulting in sustained population suppression. Through modeling, we demonstrate that iterative releases of non-biting Ifegenia males can act as an effective, confinable, controllable, and safe population suppression and elimination system.
Rational engineering of a synthetic insect-bacterial mutualism
23473Y. Su, H.-C. Lin, L. S. Teh, F. Chevance, I. James, C. Mayfield, K. G. Golic, J. A. Gagnon, O. Rog and C. Dale, Current Biology, 2022-08-29 07:21:11.
Summary Many insects maintain mutualistic associations with bacterial endosymbionts, but little is known about how they originate in nature. In this study, we describe the establishment and manipulation of a synthetic insect-bacterial symbiosis in a weevil host. Following egg injection, the nascent symbiont colonized many tissues, including prototypical somatic and germinal bacteriomes, yielding maternal transmission over many generations. We then engineered the nascent symbiont to overproduce the aromatic amino acids tyrosine and phenylalanine, which facilitate weevil cuticle strengthening and accelerated larval development, replicating the function of mutualistic symbionts that are widely distributed among weevils and other beetles in nature. Our work provides empirical support for the notion that mutualistic symbioses can be initiated in insects by the acquisition of environmental bacteria. It also shows that certain bacterial genera, including the Sodalis spp. used in our study, are predisposed to develop these associations due to their ability to maintain benign infections and undergo vertical transmission in diverse insect hosts, facilitating the partner-fidelity feedback that is critical for the evolution of obligate mutualism. These experimental advances provide a new platform for laboratory studies focusing on the molecular mechanisms and evolutionary processes underlying insect-bacterial symbiosis.
B Chromosomes in Psalidodon scabripinnis (Characiformes, Characidae) Species Complex
23552D. Silva, J. P. Castro, C. A. G. Goes, R. Utsunomia, M. R. Vidal, C. N. Nascimento, L. F. Lasmar, F. G. Paim, L. B. Soares, C. Oliveira, F. Porto-Foresti, R. F. Artoni and F. Foresti, Animals (Basel), 12. 2022-08-25 06:15:39.
B chromosomes are extra-genomic components of cells found in individuals and in populations of some eukaryotic organisms. They have been described since the first observations of chromosomes, but several aspects of their biology remain enigmatic. Despite being present in hundreds of fungi, plants, and animal species, only a small number of B chromosomes have been investigated through high-throughput analyses, revealing the remarkable mechanisms employed by these elements to ensure their maintenance. Populations of the Psalidodon scabripinnis species complex exhibit great B chromosome diversity, making them a useful material for various analyses. In recent years, important aspects of their biology have been revealed. Here, we review these studies presenting a comprehensive view of the B chromosomes in the P. scabripinnis complex and a new hypothesis regarding the role of the B chromosome in the speciation process.
Hoisted with his own petard: How sex-ratio meiotic drive in Drosophila affinis creates resistance alleles that limit its spread
23471W. J. Ma, E. M. Knoles, K. B. Patch, M. M. Shoaib and R. L. Unckless, J Evol Biol, 2022-08-23 07:13:52.
Meiotic drivers are selfish genetic elements that tinker with gametogenesis to bias their own transmission into the next generation of offspring. Such tinkering can have significant consequences on gametogenesis and end up hampering the spread of the driver. In Drosophila affinis, sex-ratio meiotic drive is caused by an X-linked complex that, when in males with a susceptible Y chromosome, results in broods that are typically more than 95% female. Interestingly, D. affinis males lacking a Y chromosome (XO) are fertile and males with the meiotic drive X and no Y produce only sons-effectively reversing the sex-ratio effect. Here, we show that meiotic drive dramatically increases the rate of nondisjunction of the Y chromosome (at least 750X), meaning that the driver is creating resistant alleles through the process of driving. We then model how the O might influence the spread, dynamics and equilibrium of the sex-ratio X chromosome. We find that the O can prevent the spread or reduce the equilibrium frequency of the sex-ratio X chromosome, and it can even lead to oscillations in frequency. Finally, with reasonable parameters, the O is unlikely to lead to the loss of the Y chromosome, but we discuss how it might lead to sex-chromosome turnover indirectly.
Genetic Tools for Integrated Management of Pests on Honeybees in the Tropics
25464M. Pattabhiramaiah, S. Mallikarjunaiah and D. Brueckner, Genetic Methods and Tools for Managing Crop Pests, 2022-08-22 09:48:31.
The Asian honeybee is endemic to Asia where it has been used for honey production and pollination services from time immemorial. They are integral to modern agricultural productivity and to survival and vitality of natural ecosystems. However, recent declines in populations and species diversity threaten both food security and natural habitats. Honeybee colonies are assaulted by numerous pests and pathogens including mites and beetles. Novel, cost-effective pest management practices are desperately needed to preserve colony health. Increased pest pressure levels justify the need for additional control methods. Beekeepers should follow the guidelines of integrated pest management (IPM) as an effective control option that will have a minimum impact on honeybee health. The use of genomic tools and engineering technologies has a great potential for enhancement and sustenance of the health of honeybees. This review focusses on the application of innovative advanced genetic tools such as SIT (sterile insect technique), genome editing, gene drive, RNAi, CRISPR/Cas9-mediated gene editing, and gene pyramiding in honeybee pest management.
Infravec2 guidelines for the design and operation of containment level 2 and 3 insectaries in Europe
23469E. Pondeville, A.-B. Failloux, F. Simard, P. Volf, A. Crisanti, R. E. Haghighat-Khah, N. Busquets, F. X. Abad, A. J. Wilson, R. Bellini, S. Marsh Arnaud, A. Kohl and E. Veronesi, Pathogens and Global Health, 2022-08-22 07:08:22.
With the current expansion of vector-based research and an increasing number of facilities rearing arthropod vectors and infecting them with pathogens, common measures for containment of arthropods as well as manipulation of pathogens are becoming essential for the design and running of such research facilities to ensure safe work and reproducibility, without compromising experimental feasibility. These guidelines and comments were written by experts of the Infravec2 consortium, a Horizon 2020-funded consortium integrating the most sophisticated European infrastructures for research on arthropod vectors of human and animal diseases. They reflect current good practice across European laboratories with experience of safely handling different mosquito species and the pathogens they transmit. As such, they provide experience-based advice to assess and manage the risks to work safely with mosquitoes and the pathogens they transmit. This document can also form the basis for research with other arthropods, for example, midges, ticks or sandflies, with some modification to reflect specific requirements.
Outbreaks of arboviruses, biotechnological innovations and vector control: facing the unexpected
23438C. Boëte, Innovative Strategies for Vector Control, 6:219-231. 2022-08-19 09:19:15.
Outbreaks of arboviruses have occurred in the last decades in many places around the world and a variety of responses have been taken in order to control them. Responses ranged from vaccination campaigns to the use of conventional vector control methods. Innovative approaches relying on biotechnological novelties, often still under development, have been considered despite the lack of solid evidence of their efficacy. While discussing these different aspects of the fight against vector-borne diseases with a focus on the context of outbreaks, this chapter considers the social and ethical aspects related to both the rhetoric and the discussion about the implementation of new and innovative approaches.
Precision Guided Sterile Males Suppress Populations of an Invasive Crop Pest
23453N. P. Kandul, J. Liu, A. Buchman, I. C. Shriner, R. M. Corder, N. Warsinger-Pepe, T. Yang, A. K. Yadav, M. J. Scott, J. M. Marshall and O. S. Akbari, GEN Biotechnology, 1:372-385. 2022-08-18 10:24:32.
The Drosophila suzukii invasion of western countries has created an immense agricultural and economic threat to crop production. Despite many attempts to suppress its population, D. suzukii continues to destroy soft-flesh fruits. Precision guided sterile insect technique (pgSIT) utilizes the accuracy of programmable CRISPR gene targeting to generate sterilized males that can be deployed to suppress populations. Here, we generate pgSIT in D. suzukii and empirically and mathematically demonstrate that sterilized males are fit, competitive, and can eliminate populations of D. suzukii. Altogether, we describe an efficient way to generate sterile D. suzukii for release and safe effective population suppression.
Environmentally appropriate vector control is facilitated by standard metrics for simulation-based evaluation
23443V. N. Vásquez, M. R. Reddy and J. M. Marshall, Frontiers in Tropical Diseases, 3. 2022-08-17 08:44:11.
As anthropogenic factors contribute to the introduction and expansion of new and established vector species, the geographic incidence of mosquito-borne disease is shifting. Computer simulations, informed by field data where possible, facilitate the cost-effective evaluation of available public health interventions and are a powerful tool for informing appropriate policy action. However, a variety of measurements are used in such assessments; this can complicate direct comparisons across both vector control technologies and the models used to simulate them. The expansion of biocontrol to include genetically engineered organisms is now prompting additional metrics with no analogy to traditional measurement approaches. We propose Standard Entomological Metrics (SEMs) to facilitate the model-based appraisal of both existing and novel intervention tools and define two examples: Suppression Efficacy Score and Time to Reduction Target. We formulate twelve synthetic case studies featuring two vector control technologies over three years of observed daily temperature in Cairns, Australia. After calculating Suppression Efficacy Score and Time to Reduction Target results, we apply these example outcomes to a discussion of health policy decision-making using SEMs. We submit that SEMs such as Suppression Efficacy Score and Time to Reduction Target facilitate the wholistic and environmentally appropriate simulation-based evaluation of intervention programs and invite the community to further discussion on this topic.
Natural selfish genetic elements should not be defined as gene drives
23435M. A. Wells and R. A. Steinbrecher, Proceedings of the National Academy of Sciences, 119:e2201142119. 2022-08-16 07:53:39.
Gene drives are increasingly discussed in the political realm,and how the term is defined therefore has important impli-cations. The opinion piece from Alphey et al. (1) identifies alack of consensus on the definition and makes explicitchanges in how the terminology is being used by someresearchers. As such it is a timely invitation for debate.The definition of the term“gene drive”Alphey et al. (1)propose would include naturally occurring selfish geneticelements (SGEs) and natural processes causing biasedinheritance. We disagree with this aspect of the proposal,which does not reflect the original use of the term, whichrelated to engineered system
A multiplexed, confinable CRISPR/Cas9 gene drive propagates in caged Aedes aegypti populations
23429M. A. E. Anderson, E. Gonzalez, M. P. Edgington, J. X. D. Ang, D.-K. Purusothaman, L. Shackleford, K. Nevard, S. A. N. Verkuijl, T. Harvey-Samuel, P. T. Leftwich, K. Esvelt and L. Alphey, bioRxiv, 2022.08.12.503466. 2022-08-12 07:19:58.
Here, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 in the germline to find an expression timing more conducive to homing. We also created a separate multiplexing (targeting multiple different sites within the target gene) sgRNA-expressing homing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene to limit the consequences of resistance alleles. This creates a ‘split’ gene drive such that one part does not drive, allowing control over geographic spread and temporal persistence. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element was driven through a cage trial population such that carrier frequency of the element increased from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.Significance statement Mosquito-borne diseases affect millions of people worldwide, with the yellow fever mosquito (Aedes aegypti) being the principal vector of many viral diseases. Effective measures for controlling this mosquito are sorely needed. Gene drive systems have arisen as a potential tool for mosquito control due to their ability of biasing inheritance of a trait into a target population. Here, we assess a split gene drive, based on CRISPR/Cas9 endonuclease technology driving a target element into the mosquito population. Evaluated over successive generations in a replicated cage trial, the drive successfully biased its inheritance, increasing in frequency from 50% to up to 89%. Our results are encouraging for the potential use of this type of contained gene drive system for mosquito control in endemic areas.Competing Interest StatementThe authors have declared no competing interest.
Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: a modeling study
23424J. Li and J. Champer, bioRxiv, 2022.08.09.503337. 2022-08-11 07:25:47.
By using both mathematical and simulation models, we found that a drive containing CifA and CifB together create a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence.
Aedes aegypti and Ae. albopictus microbiome/virome: new strategies for controlling arboviral transmission?
23413M. Gómez, D. Martinez, M. Muñoz and J. D. Ramírez, Parasites and Vectors, 15:287. 2022-08-09 12:21:12.
Aedes aegypti and Aedes albopictus are the main vectors of highly pathogenic viruses for humans, such as dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV), which cause febrile, hemorrhagic, and neurological diseases and remain a major threat to global public health. The high ecological plasticity, opportunistic feeding patterns, and versatility in the use of urban and natural breeding sites of these vectors have favored their dispersal and adaptation in tropical, subtropical, and even temperate zones. Due to the lack of available treatments and vaccines, mosquito population control is the most effective way to prevent arboviral diseases. Resident microorganisms play a crucial role in host fitness by preventing or enhancing its vectorial ability to transmit viral pathogens. High-throughput sequencing and metagenomic analyses have advanced our understanding of the composition and functionality of the microbiota of Aedes spp. Interestingly, shotgun metagenomics studies have established that mosquito vectors harbor a highly conserved virome composed of insect-specific viruses (ISV). Although ISVs are not infectious to vertebrates, they can alter different phases of the arboviral cycle, interfering with transmission to the human host. Therefore, this review focuses on the description of Ae. aegypti and Ae. albopictus as vectors susceptible to infection by viral pathogens, highlighting the role of the microbiota-virome in vectorial competence and its potential in control strategies for new emerging and re-emerging arboviruses.
Reflection on the Challenges, Accomplishments, and New Frontiers of Gene Drives
23416M. Melesse Vergara, J. Labbé and J. Tannous, BioDesign Research, 2022:9853416. 2022-08-09 07:29:59.
Ongoing pest and disease outbreaks pose a serious threat to human, crop, and animal lives, emphasizing the need for constantgenetic discoveries that could serve as mitigation strategies. Gene drives are genetic engineering approaches discovered decadesago that may allow quick, super-Mendelian dissemination of genetic modifications in wild populations, offering hopes formedicine, agriculture, and ecology in combating diseases. Following itsfirst discovery, several naturally occurring selfishgenetic elements were identified and several gene drive mechanisms that could attain relatively high threshold populationreplacement have been proposed. This review provides a comprehensive overview of the recent advances in gene drive researchwith a particular emphasis on CRISPR-Cas gene drives, the technology that has revolutionized the process of genomeengineering. Herein, we discuss the benefits and caveats of this technology and place it within the context of natural genedrives discovered to date and various synthetic drives engineered. Later, we elaborate on the strategies for designing syntheticdrive systems to address resistance issues and prevent them from altering the entire wild populations. Lastly, we highlight themajor applications of synthetic CRISPR-based gene drives in different living organisms, including plants, animals, andmicroorganisms.
Sterility of Cydia pomonella by X ray irradiation as an alternative to gamma radiation for the sterile insect technique
23463J.-H. Zhang, N. Li, H.-Y. Zhao, Y.-Q. Wang, X.-Q. Yang and K.-M. Wu, Bulletin of Entomological Research, 2022-08-06 09:27:59.
The codling moth Cydia pomonella is a major pest of global significance impacting pome fruits and walnuts. It threatens the apple industry in the Loess Plateau and Bohai Bay in China. Sterile insect technique (SIT) could overcome the limitations set by environmentally compatible area-wide integrated pest management (AW-IPM) approaches such as mating disruption and attract-kill that are difficult to suppress in a high-density pest population, as well as the development of insecticide resistance. In this study, we investigated the effects of X-ray irradiation (183, 366, 549 Gy) on the fecundity and fertility of a laboratory strain of C. pomonella, using a newly developed irradiator, to evaluate the possibility of X-rays as a replacement for Cobalt60 (60Co-γ) and the expanded future role of this approach in codling moth control. Results show that the 8th-day is the optimal age for irradiation of male pupae. The fecundity decreased significantly as the dosage of radiation increased. The mating ratio and mating number were not influenced. However, treated females were sub-sterile at a radiation dose of 183 Gy (20.93%), and were almost 100% sterile at a radiation dose of 366 Gy or higher. Although exposure to a radiation dose of 366 Gy resulted in a significant reduction in the mating competitiveness of male moths, our radiation biology results suggest that this new generation of X-ray irradiator has potential applications in SIT programs for future codling moth control.
Studies on the fitness characteristics of wMel- and wAlbB-introgressed Aedes aegypti (Pud) lines in comparison with wMel- and wAlbB-transinfected Aedes aegypti (Aus) and wild-type Aedes aegypti (Pud) lines
23485C. Sadanandane, K. Gunasekaran, D. Panneer, S. K. Subbarao, M. Rahi, B. Vijayakumar, V. Athithan, A. Sakthivel, S. Dinesh and P. Jambulingam, Frontiers in Microbiology, 13:947857. 2022-08-05 07:02:55.
Wolbachia, an intracellular maternally transmitted endosymbiont, has been shown to interfere with the replication of dengue virus in Aedes aegypti mosquitoes. The Wolbachia-transinfected Ae. aegypti has been currently released in many countries to test its effectiveness in preventing the transmission of dengue virus. ICMR-Vector Control Research Centre in collaboration with World Mosquito Program Monash University, Australia, has generated two new Wolbachia-introgressed Ae. aegypti Puducherry (Pud) lines via backcrossing Ae. aegypti females of Australian (Aus) strains, infected with wMel and wAlbB Wolbachia with wild-type Ae. aegypti Puducherry (Pud) males. Wolbachia infections are known to induce a fitness cost and confer benefit on the host mosquito populations that will influence spread of the Wolbachia into native wild mosquito populations during the field release. Hence, the induced fitness cost or benefit/advantage in the two newly generated Ae. aegypti (Pud) lines was assessed in the laboratory in comparison with the wild-type Ae. aegypti (Pud) strain. In addition, maternal transmission (MT) efficiency, induced cytoplasmic incompatibility (CI), and insecticide resistance status of the two (Pud) lines were determined to assess the likely frequency of wMel and wAlbB infections in the native wild population after field invasion. The study shows that wMel and wAlbB infections did not induce any fitness cost on the two newly generated (Pud) lines. Rather, in terms of wing length, fecundity, egg hatch rate, and adult survival, the Wolbachia introgression conferred fitness benefits on the (Pud) lines compared to uninfected Wolbachia free wild Ae. aegypti population. wMel and wAlbB exhibited a high maternal transmission (99-100%) and induced nearly complete (98-100%) cytoplasmic incompatibility. Both the (Pud) lines were resistant to deltamethrin, malathion, DDT, and temephos, and the level of resistance was almost the same between the two lines as in the wild type. Overall, the stable association of wMel and wAlbB established with Ae. aegypti and the reproductive advantages of the (Pud) lines encourage a pilot release in the field for population replacement potential.
Wolbachia Dynamics in Mosquitoes with Incomplete CI and Imperfect Maternal Transmission by a DDE System
23393Y. Su, B. Zheng and X. Zou, Bulletin of Mathematical Biology, 84:95. 2022-08-01 08:09:11.
In this paper, we propose a delay differential equation model to describe the Wolbachia infection dynamics in mosquitoes in which the key factor of cytoplasmic incompactibility (CI) is incorporated in a more natural way than those in the literature. By analyzing the dynamics of the model, we are able to obtain some information on the impact of four important parameters: the competition capabilities of the wild mosquitoes and infected mosquitoes, the maternal transmission level and the CI level. The analytic results show that there are ranges of parameters that support competition exclusion principle, and there are also ranges of parameters that allow co-persistence for both wild and infected mosquitoes. These ranges account for the scenarios of failure of invasion, invasion and suppressing the wild mosquitoes, and invasion and replacing the wild mosquitoes. We also discuss some possible future problems both in mathematics and in modeling.
A theory of resistance to multiplexed gene drive demonstrates the significant role of weakly deleterious natural genetic variation
23362B. S. Khatri and A. Burt, Proceedings of the National Academy of Sciences, 119:e2200567119. 2022-08-01 07:26:58.
CRISPR-based gene drives have the potential for controlling natural populations of disease vectors, such as malaria-carrying mosquitoes in sub-Saharan Africa. If successful, they hold promise of significantly reducing the burden of disease and death from malaria and many other vector-borne diseases. A significant challenge to success is the evolution of resistance. Here, we develop a theory of resistance for multiplexed drive, which shows the importance of weakly deleterious naturally occurring genetic variation, whose effect is significantly amplified compared to de novo mutation. These results provide a fundamental basis to estimate how many guide RNAs are required to prevent resistance in the face of natural genetic variation. Evolution of resistance is a major barrier to successful deployment of gene-drive systems to suppress natural populations, which could greatly reduce the burden of many vector-borne diseases. Multiplexed guide RNAs (gRNAs) that require resistance mutations in all target cut sites are a promising antiresistance strategy since, in principle, resistance would only arise in unrealistically large populations. Using stochastic simulations that accurately model evolution at very large population sizes, we explore the probability of resistance due to three important mechanisms: 1) nonhomologous end-joining mutations, 2) single-nucleotide mutants arising de novo, or 3) single-nucleotide polymorphisms preexisting as standing variation. Our results explore the relative importance of these mechanisms and highlight a complexity of the mutation?selection?drift balance between haplotypes with complete resistance and those with an incomplete number of resistant alleles. We find that this leads to a phenomenon where weakly deleterious naturally occurring variants greatly amplify the probability of multisite resistance compared to de novo mutation. This key result provides design criterion for antiresistance multiplexed systems, which, in general, will need a larger number of gRNAs compared to de novo expectations. This theory may have wider application to the evolution of resistance or evolutionary rescue when multiple changes are required before selection can act.
Robust control strategy by the Sterile Insect Technique for reducing epidemiological risk in presence of vector migration
23331P.-A. Bliman and Y. Dumont, Mathematical Biosciences, 350:108856. 2022-07-28 08:36:35.
The Sterile Insect Technique (SIT) is a promising technique to control mosquitoes, vectors of diseases, like dengue, chikungunya or Zika. However, its application in the field is not easy, and its success hinges upon several constraints, one of them being that the treated area must be sufficiently isolated to limit migration or re-invasion by mosquitoes from the outside. In this manuscript we study the impact of males and (fertile) females migration on SIT. We show that a critical release rate for sterile males exists for every migration level, in the context of continuous or periodic releases. In particular, when (fertile) females migration is sufficiently low, then SIT can be conducted successfully using either open-loop control or closed-loop control (or a combination of both methods) when regular measurements of the wild population are completed. Numerical simulations to illustrate our theoretical results are presented and discussed. Finally, we derive a threshold value for the females migration rate, when viruses are circulating, under which it is possible to lower the epidemiological risk in the treated area, according to the size of the human population.
Wolbachia wPip Blocks Zika Virus Transovarial Transmission in Aedes albopictus
23333Y. Guo, J. Guo, Y. Li, X. Zheng and Y. Wu, Microbiol Spectrum, e0263321. 2022-07-27 08:36:55.
Area-wide application of Wolbachia to suppress mosquito populations and their transmitted viruses has achieved success in multiple countries. However, the mass release of Wolbachia-infected male mosquitoes involves a potential risk of accidentally releasing fertile females. In this study, we employed ovarian cells of the Ae. albopictus GUA, HC, and GT lines, which exhibit key traits, and compared them to better understand how Wolbachia inhibits ZIKV transovarial transmission. Our results showed an almost complete blockade of ZIKV transmission in HC female mosquitoes. Wolbachia in natively infected GUA mosquitoes negative affected ZIKV, and this interference was shown by slightly lower loads than those in HC mosquitoes. Overall, our work helps show how Wolbachia blocks ZIKV expansion and maintenance in the ovaries of Ae. albopictus and aids in understanding Wolbachia-ZIKV interactions in mosquitoes.
