Scholarly Literature
This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives). The latest are shown here.
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Wolbachia Induces Structural Defects Harmful to Drosophila simulans Riverside Spermiogenesis.
28142M. G. Riparbelli, A. Pratelli and G. Callaini, Cells, 12. 2023-09-21 10:31:00.
The relationship between cytoplasmic incompatibility and the obligate intracellular alphaproteobacteria Wolbachia has for a long time been reported. Although the molecular mechanisms responsible for this reproductive alteration are beginning to be understood, the effects of Wolbachia on germ cell structure and dynamics have not yet been fully investigated. We report here that the presence of Wolbachia in infected cysts of elongating spermatids is associated with major structural defects that become more evident in mature sperm. We find mitochondrial defects, an improper axoneme structure, reduced sperm numbers, and individualization failures. The large heterogeneous variety of the ultrastructural defects found in elongating spermatids and mature sperm provide the first cytological evidence for the reduced fertility associated with Wolbachia infection in Drosophila simulans males. The observed abnormalities could be the result of the mechanical stress induced by the high bacteria numbers during the process of spermatid elongation, rather than the result of the released factors affecting the proper morphogenesis of the germ cells. Moreover, high Wolbachia densities in male germ cells may not be appropriate for causing cytoplasmic incompatibility as the bacteria are harmful for spermatid differentiation, leading to abnormal sperm that is unlikely to be functional.
Effect of 2 sex-sorting time schedules on SIT facility management
28345M. Malfacini, A. Puggioli, F. Balestrino, M. Carrieri, M. L. Dindo and R. Bellini, Journal of Insect Science, 23:9. 2023-09-18 10:58:06.
Improvements are needed in mosquito mass-rearing to effectively implement the sterile insect technique (SIT). However, managing this technique is challenging and resource intensive. SIT relies on mass rearing, sterilization, and release of adult males to reduce field populations. Maintaining an acceptable level of female presence, who can transmit viruses through biting, is crucial. Females are also essential for facility sustainability. Sex sorting plays a vital role in the production process, and our current mechanical sorting approach aims to obtain a high number of adult males with minimal female contamination within 24 h of pupation. Utilizing protandry helps control female contamination. While the 24-h sorting period achieves desired contamination levels, it may not yield enough females to sustain breeding lines, leading to increased labor costs that impact project sustainability. By delaying the sorting procedure to 48 h, we obtained sufficient females to sustain breeding lines, achieving a balance between male production and female contamination using the automatic version of the Fay–Morlan device as the sorting tool.
Development and characterization of microsatellite markers for the tsetse species Glossina brevipalpis and preliminary population genetics analyses
27882F. Gstöttenmayer, P. Moyaba, M. Rodriguez, F. C. Mulandane, H. N. Mucache, L. Neves, C. De Beer, S. Ravel, T. De Meeûs, R. L. Mach, M. J. B. Vreysen and A. M. M. Abd-Alla, Parasite, 30:34. 2023-09-15 08:27:06.
Tsetse flies, the vectors of African trypanosomes are of key medical and economic importance and one of the constraints for the development of Africa. Tsetse fly control is one of the most effective and sustainable strategies used for controlling the disease. Knowledge about population structure and level of gene flow between neighbouring populations of the target vector is of high importance to develop appropriate strategies for implementing effective management programmes. Microsatellites are commonly used to identify population structure and assess dispersal of the target populations and have been developed for several tsetse species but were lacking for Glossina brevipalpis. In this study, we screened the genome of G. brevipalpis to search for suitable microsatellite markers and nine were found to be efficient enough to distinguish between different tsetse populations. The availability of these novel microsatellite loci will help to better understand the population biology of G. brevipalpis and to assess the level of gene flow between different populations. Such information will help with the development of appropriate strategies to implement the sterile insect technique (SIT) in the framework of an area-wide integrated pest management (AW-IPM) approach to manage tsetse populations and ultimately address the trypanosomoses problem in these targeted areas.
Quantifying Fitness Costs in Transgenic Aedes aegypti Mosquitoes
27981I. Sanchez-Vargas, A. E. Williams, L. E. Martin, I. Martin-Martin, S. Bennett, K. E. Olson and E. Calvo, Journal of Visualized Experiments, 2023-09-15 07:51:42.
Transgenic mosquitoes often display fitness costs compared to their wild-type counterparts. In this regard, fitness cost studies involve collecting life parameter data from genetically modified mosquitoes and comparing them to mosquitoes lacking transgenes from the same genetic background. This manuscript illustrates how to measure common life history traits in the mosquito Aedes aegypti, including fecundity, wing size and shape, fertility, sex ratio, viability, development times, male contribution, and adult longevity. These parameters were chosen because they reflect reproductive success, are simple to measure, and are commonly reported in the literature. The representative results quantify fitness costs associated with either a gene knock-out or a single insertion of a gene drive element. Standardizing how life parameter data are collected is important because such data may be used to compare the health of transgenic mosquitoes generated across studies or to model the transgene fixation rate in a simulated wild-type mosquito population. Although this protocol is specific for transgenic Aedes aegypti, the protocol may also be used for other mosquito species or other experimental treatment conditions, with the caveat that certain biological contexts may require special adaptations.
Using Wolbachia to control rice planthopper populations: progress and challenges
27976Y. Guo, J. Shao, Y. Wu and Y. Li, Frontiers in Microbiology, 14. 2023-09-14 07:43:50.
Wolbachia have been developed as a tool for protecting humans from mosquito populations and mosquito-borne diseases. The success of using Wolbachia relies on the facts that Wolbachia are maternally transmitted and that Wolbachia-induced cytoplasmic incompatibility provides a selective advantage to infected over uninfected females, ensuring that Wolbachia rapidly spread through the target pest population. Most transinfected Wolbachia exhibit a strong antiviral response in novel hosts, thus making it an extremely efficient technique. Although Wolbachia has only been used to control mosquitoes so far, great progress has been made in developing Wolbachia-based approaches to protect plants from rice pests and their associated diseases. Here, we synthesize the current knowledge about the important phenotypic effects of Wolbachia used to control mosquito populations and the literature on the interactions between Wolbachia and rice pest planthoppers. Our aim is to link findings from Wolbachia-mediated mosquito control programs to possible applications in planthoppers.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti
27839Reitmayer, Christine M. Levitt, Emily Basu, Sanjay Atkinson, Barry Fragkoudis, Rennos Merits, Andres Lumley, Sarah Larner, Will Diaz, Adriana V. Rooney, Sara Thomas, Callum J. E. von Wyschetzki, Katharina Rausalu, Kai Alphey, Luk, Proceedings of the National Academy of Sciences, 120:e2303080120. 2023-09-12 09:18:45.
Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1?nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.
MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance
27894A. Mondal, C. H. M. Sanchez and J. M. Marshall, bioRxiv, 2023.09.09.556958. 2023-09-12 08:11:56.
We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided.
Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia
27831Ogunlade, S. T. Adekunle, A. I. Meehan, M. T. McBryde, E. S., Scientific Reports, 13:14932. 2023-09-11 08:51:39.
From October 2014 to February 2019, local authorities in Townsville, North Queensland, Australia continually introduced Wolbachia-infected mosquitoes to control seasonal outbreaks of dengue infection. In this study, we develop a mathematical modelling framework to estimate the effectiveness of this intervention as well as the relative dengue transmission rates of Wolbachia-infected and wild-type mosquitoes. We find that the transmission rate of Wolbachia-infected mosquitoes is reduced approximately by a factor of 20 relative to the uninfected wild-type population. In addition, the Townsville Wolbachia release program led to a 65% reduction in predicted dengue incidence during the release period and over 95% reduction in the 24 months that followed. Finally, to investigate the potential impact of other Wolbachia release programs, we use our estimates of relative transmissibility to calculate the relationship between the reproductive number of dengue and the proportion of Wolbachia-infected mosquitoes in the vector population.
New perspectives on the causes and consequences of male meiotic drive
27827Courret, Cécile Wei, Xiaolu Larracuente, Amanda M., Current Opinion in Genetics & Development, 2023-09-11 08:34:27.
Gametogenesis is vulnerable to selfish genetic elements that bias their transmission to the next generation by cheating meiosis. These so-called meiotic drivers are widespread in plants, animals, and fungi and can impact genome evolution. Here, we summarize recent progress on the causes and consequences of meiotic drive in males, where selfish elements attack vulnerabilities in spermatogenesis. Advances in genomics provide new insights into the organization and dynamics of driving chromosomes in natural populations. Common themes, including small RNAs, gene duplications, and heterochromatin, emerged from these studies. Interdisciplinary approaches combining evolutionary genomics with molecular and cell biology are beginning to unravel the mysteries of drive and suppression mechanisms. These approaches also provide insights into fundamental processes in spermatogenesis and chromatin regulation.
Rodents as vehicle for delivery of transgenic bacteria to make paratransgenic sand fly vectors of cutaneous leishmaniasis in field condition
Ghassemi, Marzieh Akhavan, Amir Ahmad Zahraei-Ramazani, Alireza Yakhchali, Bagher Arandian, Mohammad Hossein Jafari, Reza Akhlaghi, Maryam Shirani-Bidabadi, Leila Azam, Kamal Koosha, Mona Oshaghi, Mohammad Ali, Scientific Reports, 13:14912. 2023-09-09 08:43:21.Vector-borne diseases, among them leishmaniasis, cause more than 700,000 deaths annually. The lack of an effective vaccination and the increasing resistance of sand flies to insecticides require the urgent development of innovative approaches to contain the disease. The use of engineered bacteria that express anti-parasite molecules (paratransgenesis) shows much promise. However, a challenge for implementation of this strategy is to devise means to introduce modified bacteria into sand flies in the field. In this study, we use rodent food bait as a delivery strategy to introduce two mCherry-fluorescent bacteria, Serratia AS1 and Enterobacter cloacae, into adult sand flies in field settings. Bacteria-infected food was provided to Rhombomys opimus rodents. These bacteria transiently pass through the rodent alimentary tract and are delivered to larval habitats with the rodent feces. The feces are ingested by sand fly larvae and, in the case of Serratia AS1, are trans-stadially transmitted to adults. This is the first report of targeting delivery of Serratia AS1 in a paratransgenic system to control transmission of leishmaniasis under field condition. This novel strategy shows promise for delivering transgenic bacteria to Leishmania vectors in the field.
Molecular Evidence of Wolbachia Species in Wild-Caught Aedes albopictus and Aedes aegypti Mosquitoes in Four States of Northeast India
27843Vinayagam, S. Nirmolia, T. Chetry, S. Kumar, N. P. Saini, P. Bhattacharyya, D. R. Bhowmick, I. P. Sattu, K. Patgiri, S. J., Journal of Tropical Medicine, 2023-09-05 09:37:52.
Wolbachia, a Gram-negative intracellular bacterium, naturally infects many arthropods, including mosquito vectors responsible for the spread of arboviral diseases such as Zika, chikungunya, and dengue fever. Certain Wolbachia strains are involved in inhibiting arbovirus replication in mosquitoes, and this phenomenon is currently being studied to combat disease vectors. A study was conducted in four states in north-eastern India to investigate the presence of natural Wolbachia infection in wild-caught Aedes albopictus and Aedes aegypti mosquitoes, the established vectors of dengue. The detection of a Wolbachia infection was confirmed by nested PCR and sequencing in the two mosquito species Ae. aegypti and Ae. albopictus. Positivity rates observed in Ae. aegypti and Ae. albopictus pools were 38% (44 of 115) and 85% (41 of 48), respectively, and the difference was significant (chi-square = 28.3174, p = 0.00000010). Sequencing revealed that all detected Wolbachia strains belonged to supergroup B. Although Wolbachia infection in Ae. aegypti has been previously reported from India, no such reports are available from north-eastern India. Data on naturally occurring Wolbachia strains are essential for selecting the optimal strain for the development of Wolbachia-based control measures. This information will be helpful for the future application of Wolbachia-based vector control measures in this part of the country.
Jamestown Canyon virus is transmissible by Aedes aegypti and is only moderately blocked by Wolbachia co-infection
27755M. J. Lau, H. L. C. Dutra, M. J. Jones, B. P. McNulty, A. M. Diaz, F. Ware-Gilmore and E. A. McGraw, PLOS Neglected Tropical Diseases, 17. 2023-09-05 07:50:16.
Jamestown Canyon virus (JCV), a negative-sense arbovirus, is increasingly common in the upper Midwest of the USA. Transmitted by a range of mosquito genera, JCV's primary amplifying host is white-tailed deer. Aedes aegypti is responsible for transmitting various positive-sense viruses globally including dengue (DENV), Zika, chikungunya, and Yellow Fever. Ae. aegypti's distribution, once confined to the tropics, is expanding, in part due to climate change. Wolbachia, an insect endosymbiont, limits the replication of co-infecting viruses inside insects. The release and spread of the symbiont into Ae. aegypti populations have been effective in reducing transmission of DENV to humans, although the mechanism of Wolbachia-mediated viral blocking is still poorly understood. Here we explored JCV infection potential in Ae. aegypti, the nature of the vector's immune response, and interactions with Wolbachia infection. We show that Ae. aegypti is highly competent for JCV, which grows to high loads and rapidly reaches the saliva after an infectious blood meal. The mosquito immune system responds with strong induction of RNAi and JAK/STAT. Neither the direct effect of viral infection nor the energetic investment in immunity appears to affect mosquito longevity. Wolbachia infection blocked JCV only in the early stages of infection. Wolbachia-induced immunity was small compared to that of JCV, suggesting innate immune priming does not likely explain blocking. We propose two models to explain why Wolbachia's blocking of negative-sense viruses like JCV may be less than that of positive-sense viruses, relating to the slowdown of host protein synthesis and the triggering of interferon-like factors like Vago. In conclusion, we highlight the risk for increased human disease with the predicted future overlap of Ae. aegypti and JCV ranges. We suggest that with moderate Wolbachia-mediated blocking and distinct biology, negative-sense viruses represent a fruitful comparator model to other viruses for understanding blocking mechanisms in mosquitoes.
The role of conflict in shaping plant biodiversity
27753J. M. Coughlan, New Phytologist, 2023-09-04 07:45:46.
Although intrinsic postzygotic reproductive barriers can play a fundamental role in speciation, their underlying evolutionary causes are widely debated. One hypothesis is that incompatibilities result from genomic conflicts. Here, I synthesize the evidence that conflict generates incompatibilities in plants, thus playing a creative role in plant biodiversity. While much evidence supports a role for conflict in several classes of incompatibility, integrating knowledge of incompatibility alleles with natural history can provide further essential tests. Moreover, comparative work can shed light on the relative importance of conflict in causing incompatibilities, including the extent to which their evolution is repeatable. Together, these approaches can provide independent lines of evidence that conflict causes incompatibilities, cementing its role in plant speciation.
Transgenic approaches in medical entomology: 2022 highlights
27751M. L. Simões, Journal of Medical Entomology, tjad105. 2023-09-02 07:40:51.
Transgenesis has emerged as a powerful tool to control arthropod vectors and the diseases they transmit. Here, we highlight the latest developments on transgenic approaches in ticks, Anopheles and Aedes mosquitoes, based on recent findings and significant papers from 2022. We survey topics ranging from population replacement, population suppression, gene drive, sex ratio distortion, public engagement and capacity building, and gene editing in ticks. While presenting these advancements, we discuss the current challenges surrounding the application of arthropod transgenesis for the development of novel vector control strategies.
Meiotic segregation and post-meiotic drive of the Festuca pratensis B chromosome
27749R. Ebrahimzadegan, J. Fuchs, J. Chen, V. Schubert, A. Meister, A. Houben and G. Mirzaghaderi, Chromosome Research, 31:26. 2023-09-02 07:34:43.
In many species, the transmission of B chromosomes (Bs) does not follow the Mendelian laws of equal segregation and independent assortment. This deviation results in transmission rates of Bs higher than 0.5, a process known as “chromosome drive”. Here, we studied the behavior of the 103 Mbp-large B chromosome of Festuca pratensis during all meiotic and mitotic stages of microsporogenesis. Mostly, the B chromosome of F. pratensis segregates during meiosis like standard A chromosomes (As). In some cases, the B passes through meiosis in a non-Mendelian segregation leading to their accumulation already in meiosis. However, a true drive of the B happens during the first pollen mitosis, by which the B preferentially migrates to the generative nucleus. During second pollen mitosis, B divides equally between the two sperms. Despite some differences in the frequency of drive between individuals with different numbers of Bs, at least 82% of drive was observed. Flow cytometry-based quantification of B-containing sperm nuclei agrees with the FISH data.
A synthetic biology approach to transgene expression
27699P. Leftwich, T. , J. Purcell, C. , M. Anderson, A. E. , R. Fragkoudis, S. Basu, G. Lycett, T. and L. Alphey, bioRxiv, 2023.08.31.555539. 2023-08-31 09:13:32.
The ability to control gene expression is pivotal in genetic engineering and synthetic biology. However, in most non-model and pest insect species, empirical evidence for predictable modulation of gene expression levels is lacking. This knowledge gap is critical for genetic control systems, particularly in mosquitoes, where transgenic methods offer novel routes for pest control. Commonly, the choice of RNA polymerase II promoter (Pol II) is the primary method for controlling gene expression, but the options are limited. To address this, we developed a systematic approach to characterize modifications in translation initiation sequences (TIS) and 3' untranslated regions (UTR) of transgenes, enabling the creation of a toolbox for gene expression modulation in mosquitoes and potentially other insects. The approach demonstrated highly predictable gene expression changes across various cell lines and promoter sequences, representing a significant advancement in mosquito synthetic biology gene expression.Competing Interest StatementThe authors have declared no competing interest.
Does ignoring transmission dynamics lead to underestimation of the impact of interventions against mosquito-borne disease?
27695S. Cavany, J. Huber, H. , A. Wieler, Q. M. Tran, M. Alkuzweny, M. Elliott, G. España, S. Moore, M. and T. A. Perkins, BMJ Global Health, 8:e012169. 2023-08-31 09:07:49.
New vector-control technologies to fight mosquito-borne diseases are urgently needed, the adoption of which depends on efficacy estimates from large-scale cluster-randomised trials (CRTs). The release of Wolbachia-infected mosquitoes is one promising strategy to curb dengue virus (DENV) transmission, and a recent CRT reported impressive reductions in dengue incidence following the release of these mosquitoes. Such trials can be affected by multiple sources of bias, however. We used mathematical models of DENV transmission during a CRT of Wolbachia-infected mosquitoes to explore three such biases: human movement, mosquito movement and coupled transmission dynamics between trial arms. We show that failure to account for each of these biases would lead to underestimated efficacy, and that the majority of this underestimation is due to a heretofore unrecognised bias caused by transmission coupling. Taken together, our findings suggest that Wolbachia-infected mosquitoes could be even more promising than the recent CRT suggested. By emphasising the importance of accounting for transmission coupling between arms, which requires a mathematical model, we highlight the key role that models can play in interpreting and extrapolating the results from trials of vector control interventions.Data are available in a public, open access repository. All code and other files to reproduce our results is available at: https://github.com/scavany/awed_trial_modeling/
Wolbachia wMel strain-mediated effects on dengue virus vertical transmission from Aedes aegypti to their offspring
27693K. Duong Thi Hue, D. da Silva Goncalves, V. Tran Thuy, L. Thi Vo, D. Le Thi, N. Vu Tuyet, G. Nguyen Thi, T. Huynh Thi Xuan, N. Nguyen Minh, P. Nguyen Thanh, S. Yacoub and C. P. Simmons, Parasites and Vectors, 16:308. 2023-08-31 08:53:50.
Background Dengue virus serotypes (DENV-1 to -4) can be transmitted vertically in Aedes aegpti mosquitoes. Whether infection with the wMel strain of the endosymbiont Wolbachia can reduce the incidence of vertical transmission of DENV from infected females to their offspring is not well understood. Methods A laboratory colony of Vietnamese Ae. aegypti, both with and without wMel infection, were infected with DENV-1 by intrathoracic injection (IT) to estimate the rate of vertical transmission (VT) of the virus. VT in the DENV-infected mosquitoes was calculated via the infection rate estimation from mosquito pool data using maximum likelihood estimation (MLE). Results In 6047 F1 Vietnamese wild-type Ae. aegypti, the MLE of DENV-1 infection was 1.49 per 1000 mosquitoes (95% confidence interval [CI] 0.73–2.74). In 5500 wMel-infected Ae. aegypti, the MLE infection rate was 0 (95% CI 0–0.69). The VT rates between mosquito lines showed a statistically significant difference. Conclusions The results reinforce the view that VT is a rare event in wild-type mosquitoes and that infection with wMel is effective in reducing VT.
A migration-selection model in genetic engineering
27690Y. Qi and L. Su, Nonlinear Analysis: Real World Applications, 75:103983. 2023-08-31 08:48:22.
We investigate a migration-selection system arising from CRISPR-Cas9 genetic engineering, which describes the evolution of the frequencies of a wild allele O, a drive allele D, and a brake allele B. The purpose is to see whether the drive allele D can persist in the population and whether its spread can be limited or stopped by the brake allele B when necessary. We give a complete classification of the dynamics of this system when there is no migration. We further show that migration may cause complex spatiotemporal patterns by demonstrating the existence of spatially inhomogeneous periodic solutions and steady state solutions.

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