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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Susceptibility of Wolbachia mosquito control to temperature shifts

27579
E. P. Caragata,  Nature Climate Change,  13:767-768. 2023-08-01 08:10:19.
Vásquez and colleagues consider the potential impacts of increasing and variable temperatures on Wolbachia-based population-replacement interventions. Previous laboratory experiments have highlighted the temperature-sensitive nature of Wolbachia, with high average daily temperatures and prolonged heatwaves potentially decreasing Wolbachia titre, leading to weakening or loss of maternal transmission, cytoplasmic incompatibility and virus blocking . In nature, this could potentially hinder or thwart interventions. Vásquez and colleagues use Coupled Model Intercomparison Project Phase 5 climate projections to model the efficacy of population-replacement interventions utilizing the wMel Wolbachia strain in Ae. aegypti in Cairns, Australia, and in Nha Trang, Vietnam, two current intervention sites. Their mechanistic models compare population-replacement efficiency under current temperature regimes, and those projected for the 2030s (2024–2039) and 2050s (2044–2059). These models also incorporate loss of wMel infection at an average daily temperature threshold of 35 °C (based on laboratory data ), or more stringently, at 33 °C or 31.5 °C.

Ability of a selfish B chromosome to evade genome elimination in the jewel wasp, Nasonia vitripennis

27561
H. Lee, P. Seo, S. Teklay, E. Yuguchi, E. D. Benetta, J. H. Werren and P. M. Ferree,  Heredity,  2023-07-31 07:06:11.
B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR's own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp's genome also seem to evade chromatin disruption by PSR, suggesting that PSR's genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.

X chromosome drive is constrained by sexual selection and influences ornament evolution

27304
K. A. Paczolt, G. T. Welsh and G. S. Wilkinson,  Proceedings of the Royal Society B: Biological Sciences,  290:20230929. 2023-07-26 07:17:43.
Experimental evolution provides an integrative method for revealing complex interactions among evolutionary processes. One such interaction involves sex-linked selfish genetic elements and sexual selection. X-linked segregation distorters, a type of selfish genetic element, influence sperm transmission to increase in frequency and consequently alter the population sex ratio and the opportunity for sexual selection, while sexual selection may impact the spread of X-linked distorters. Here we manipulated sexual selection by controlling female mating opportunities and the presence of a distorting X chromosome in experimental lines of the stalk-eyed fly, Teleopsis dalmanni, over 11 generations. We find that removal of sexual selection leads to an increase in the frequency of the X-linked distorter and sex ratio across generations and that post-copulatory sexual selection alone is sufficient to limit the frequency of distorters. In addition, we find that male eyestalk length, a trait under pre-copulatory sexual selection, evolves in response to changes in the strength of sexual selection with the magnitude of the response dependent on X chromosome type and the frequency of distorting X chromosomes. These results reveal how a selfish X can interact with sexual selection to influence the evolution of sexually selected traits in multiple ways.

Effects of γ-Irradiation on Mating Behavior of Red Palm Weevil, Rhynchophorus ferrugineus (Olivier, 1790) (Coleoptera: Dryophthoridae)

27600
M. Cristofaro, C. Fornari, F. Mariani, A. Cemmi, M. Guedj, M. L. Ben Jamaa, M. Msaad Guerfali, E. Tabone, R. Castellana, R. Sasso and S. Musmeci,  Insects,  14. 2023-07-24 07:00:32.
Red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier 1790) is a highly invasive species originating from Southeast Asia and Melanesia. Over the past 30 years, this alien pest has spread extensively in the Middle East and the Mediterranean basin. Its endophagous larvae feed on various palm species, causing significant damage that leads to the death of palm trees. Controlling RPW infestations is challenging due to their gregarious nature and the lack of detectable early symptoms. Systemic insecticides are effective means of control, but their use in urban areas is prohibited and resistance can develop. Considering alternative options with minimal environmental impact, the Sterile Insect Technique (SIT) has been explored. Previous research has shown that male RPWs irradiated at 80 Gy or higher achieve full sterility. This study aimed to investigate in laboratory conditions whether RPW sterile males (irradiated at 60 and 80 Gy) could compete sexually with non-irradiate males. Laboratory bio-assays under both no-choice and choice conditions assessed sexual performance in terms of number of matings, mating duration and time elapsed until the first mating. The results confirmed that irradiation does not negatively affect the mating performance of sterile males, demonstrating their ability to compete successfully with non-irradiated males in both experimental setups.

First Detection and Genetic Identification of Wolbachia Endosymbiont in Field-Caught Aedes aegypti (Diptera: Culicidae) Mosquitoes Collected from Southern Taiwan

27713
L.-L. Chao and C.-M. Shih,  Microorganisms,  11. 2023-07-23 09:53:12.
The prevalence and genetic character of Wolbachia endosymbionts in field-collected Aedes aegypti mosquitoes were examined for the first time in Taiwan. A total of 665 Ae. aegypti were screened for Wolbachia infection using a PCR assay targeting the Wolbachia surface protein (wsp) gene. In general, the prevalence of Wolbachia infection was detected in 3.3% Ae. aegypti specimens (2.0% female and 5.2% male). Group-specific Wolbachia infection was detected with an infection rate of 1.8%, 0.8% and 0.8% in groups A, B and A&B, respectively. Genetic analysis demonstrated that all Wolbachia strains from Taiwan were phylogenetically affiliated with Wolbachia belonging to the supergroups A and B, with high sequence similarities of 99.4–100% and 99.2–100%, respectively. Phylogenetic relationships can be easily distinguished by maximum likelihood (ML) analysis and were congruent with the unweighted pair group with the arithmetic mean (UPGMA) method. The intra- and inter-group analysis of genetic distance (GD) values revealed a lower level within the Taiwan strains (GD < 0.006 for group A and GD < 0.008 for group B) and a higher level (GD > 0.498 for group A and GD > 0.286 for group B) as compared with other Wolbachia strains. Our results describe the first detection and molecular identification of Wolbachia endosymbiont in field-caught Ae. aegypti mosquitoes collected from Taiwan, and showed a low Wolbachia infection rate belonging to supergroups A and B in Ae. aegypti mosquitoes.

Cost-effectiveness of Precision Guided SIT for Control of Anopheles gambiae in the Upper River Region, The Gambia

27060
G. William, R. Robyn, M. Agastya, M. S. C. Hector, S. Andrea, Z. David, G. I. Patrick, D. Umberto, Alessandro, M. M. John and A. Omar,  bioRxiv,  2023.07.20.549762. 2023-07-22 06:41:45.
Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. Here we explore the cost effectiveness of using this approach in Africa using mathematical modeling and economical analysis. Overall, we find that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits.Competing Interest StatementThis work was supported by funding from an Open Philanthropy award (309937-0001). The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government. Figures were created using www.BioRender.com.

Eliminating Malaria Vectors with Precision Guided Sterile Males

27058
L. S. Andrea, A. A. Reema, J. P. James, L. C. Martha, C. Sanle, M. Agastya, M. S. C. Hector, A. Igor, M. M. John and S. A. Omar,  bioRxiv,  2023.07.20.549947. 2023-07-21 06:35:41.
Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass-releases of non-biting, non-driving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here we develop precision guided Sterile Insect Technique (pgSIT) in the mosquito A. gambiae for inducible, programmed male-sterilization and female-elimination for wide scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding &gt;99.5% male-sterility and &gt;99.9% female-lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, for the first time enabling scalable SIT-like confinable suppression in the species.Competing Interest StatementO.S.A is a founder of Agragene, Inc. and Synvect, Inc. with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All other authors declare no competing interests.

A natural gene drive system confers reproductive isolation in rice

27420
C. Wang, J. Wang, J. Lu, Y. Xiong, Z. Zhao, X. Yu, X. Zheng, J. Li, Q. Lin, Y. Ren, Y. Hu, X. He, C. Li, Y. Zeng, R. Miao, M. Guo, B. Zhang, Y. Zhu, Y. Zhang, W. Tang, Y. Wang, B. Hao, Q. Wang, S. Cheng, X. He, B. Yao, J. Gao, X. Zhu, H. Yu, Y. Wang, Y. S,  Cell,  2023-07-20 08:38:37.
Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two genes (iORF3/DUYAO and iORF4/JIEYAO) that confer preferential transmission of the RHS12-i type male gamete into the progeny, thereby forming a natural gene drive. DUYAO encodes a mitochondrion-targeted protein that interacts with OsCOX11 to trigger cytotoxicity and cell death, whereas JIEYAO encodes a protein that reroutes DUYAO to the autophagosome for degradation via direct physical interaction, thereby detoxifying DUYAO. Evolutionary trajectory analysis reveals that this system likely formed de novo in the AA genome Oryza clade and contributed to reproductive isolation (RI) between different lineages of rice. Our combined results provide mechanistic insights into the genetic basis of RI as well as insights for strategic designs of hybrid rice breeding.

Population suppression by release of insects carrying a dominant sterile homing gene drive targeting doublesex in Drosophila

26903
C. Weizhe, G. Jialiang, L. Yiran and C. Jackson,  bioRxiv,  2023.07.17.549342. 2023-07-17 11:00:13.
Gene drive alleles, which bias their own inheritance and increase in frequency, show great promise for blocking disease transmission or directly suppressing pest populations. The most common engineered drive system is the CRISPR homing drive, which converts wild-type alleles to drive alleles in the germline of drive heterozygotes by homology-directed repair after CRISPR cleavage. One successful homing drive example targets a female-specific exon in doublesex in Anopheles mosquitos, suppressing the population by inducing recessive sterility in female drive homozygotes. We found that in Drosophila melanogaster, a 3-gRNA drive disrupting the doublesex female exon resulted in a masculine phenotype and dominant female sterility. Resistance alleles formed by end-joining repair were also dominant sterile. This was likely caused by expression of male-specific transcripts in females with drive and resistance alleles, disrupting sex development. Based on this construct, we proposed a new pest suppression system called Release of Insects carrying a Dominant-sterile Drive (RIDD). This entails continuously releasing drive heterozygous males, with drive and resistance alleles causing sterility in females. The drive remains at high frequency longer than currently used dominant female-lethal alleles (RIDL) due to drive conversion in males, and drive alleles also cause sterility based on resistance, both substantial advantages. With weekly releases of drive males into a cage population with overlapping generations, our RIDD system targeting dsx reached 100% prevalence within 27 weeks, progressively reducing egg production and eventually causing total population collapse. RIDD combines the merits of homing gene drive and RIDL. It is powerful but self-limiting, unlike unconfined standard homing drives, allowing for targeted population suppression.Competing Interest StatementThe authors have declared no competing interest.

Modeling the Impact of Migration on Mosquito Population Suppression

27422
M. Huang and J. Yu,  Qualitative Theory of Dynamical Systems,  22:134. 2023-07-17 08:45:23.
The Wolbachia-induced incompatible insect technique is a promising strategy for controlling wild mosquito populations. However, recent experimental studies have shown that mosquito migration into target areas dilutes the strategy’s effectiveness. In this work, we formulate a delay differential equation model to assess the impact of migration on mosquito population suppression. We identify that mosquito migration into an idealized target area makes it impossible to eliminate the target population completely. Our analysis identifies a lower bound of the suppression rate $$gamma ^*$$for a given migration number, which reveals the possible maximum reduction of wild population size in the peak season. For a given suppression rate target $$gamma _0>gamma ^*$$, we identify the permitted maximum migration number $$D(gamma _0)$$, above which is impossible to reduce the field mosquito density up to $$(1-gamma _0)times 100%$$in peak season. To reduce more than $$95%$$of Aedes albopictus population during its peak season in Guangzhou within six weeks, the required minimum release number of Wolbachia-infected males climbs steeply as the migration number increases to D(0.05).

Engineered Gut Symbiotic Bacterium-Mediated RNAi for Effective Control of Anopheles Mosquito Larvae

27559
J. J. Ding, C. L. Cui, G. D. Wang, G. Wei, L. Bai, Y. F. Li, P. L. Sun, L. Dong, Z. C. Liu, J. Q. Yun, F. Li, K. Li, L. He and S. B. Wang,  Microbiology Spectrum,  2023-07-17 06:46:02.
Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria.IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control. Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides.

New germline Cas9 promoters show improved performance for homing gene drive

26623
D. Jie, C. Weizhe, J. Xihua, X. Xuejiao, Y. Emily, Z. Ruizhi, Z. Yuqi, M. Matt, W. M. Philipp and C. Jackson,  bioRxiv,  2023.07.16.549205. 2023-07-16 08:48:12.
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives, perhaps the most powerful gene drive strategy, convert wild type alleles into drive alleles in heterozygotes with the help of Cas9 and gRNA. However, achieving successful outcomes with these drives often requires high performance. Specifically, it is desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. Thus far, high-performance promoters have only been discovered in Anopheles species. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we tested eleven Drosophila melanogaster germline promoters in several configurations. Some of the new promoters achieved higher drive conversion efficiency with minimal embryo resistance, but none could completely avoid somatic expression like nanos. However, such somatic expression often did not carry detectable fitness costs when the promoter-Cas9 elements supported a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Based on our findings, we selected two Cas9 promoter lines for cage experiments with a 4-gRNA suppression drive. While one promoter exhibited substantial somatic effects, leading to a low drive equilibrium frequency, the other outperformed nanos, resulting in the successful suppression of the cage population. Overall, these novel Cas9 promoters hold potential advantages for homing drives in Drosophila species and may also possess valuable homologs in other organisms.Competing Interest StatementThe authors have declared no competing interest.

Optimization of Dieldrin Selection for the Genetic Sexing of Aedes albopictus

26598
S. Scussel, B. Gaudillat, J. Esnault, Q. Lejarre, M. Duployer, D. Messaoudi, P. Mavingui, P. Tortosa and J. Cattel,  Insects,  14. 2023-07-13 12:55:46.
The mass production of mosquitoes at an industrial scale requires efficient sex separation, which can be achieved through mechanical, genetic or artificial intelligence means. Compared with other methods, the genetic sexing approach offers the advantage of limiting costs and space by removing females at the larval stage. We recently developed a Genetic Sexing Strain (GSS) in Aedes albopictus based on the sex linkage of the rdlR allele, conferring resistance to dieldrin, to the male (M) locus. It has been previously reported that dieldrin ingested by larvae can be detected in adults and bioaccumulated in predators, raising the question of its use at a large scale. In this context, we performed several experiments aiming at optimizing dieldrin selection by decreasing both dieldrin concentration and exposure time while maintaining a stable percentage of contaminating females averaging 1%. We showed that the previously used dieldrin exposure induced an important toxicity as it killed 60% of resistant males at the larval stage. We lowered this toxicity by reducing the dose and/or the exposure time to recover nearly all resistant males. We then quantified the residues of dieldrin in resistant male adults and showed that dieldrin toxicity in larvae was positively correlated with dieldrin concentrations detected in adults. Interestingly, we showed that the use of reduced dieldrin exposure led to a dieldrin quantification in adult males that was below the quantity threshold of the Gas Chromatography-Mass Spectrometry detection method. Presented data show that dieldrin exposure can be adjusted to suppress toxicity in males while achieving efficient sexing and lowering the levels of dieldrin residues in adults to barely quantifiable levels.

Teosinte Pollen Drive guides maize domestication and evolution by RNAi

27414
B. Berube , E. Ernst, J. Cahn, B. Roche, C. d. S. Alves, A. Scheben, A. Siepel, J. Ross-Ibarra, J. Kermicle and R. Martienssen,  bioRxiv,  2023.07.12.548689. 2023-07-13 08:27:36.
Meiotic drivers subvert Mendelian expectations by manipulating reproductive development to bias their own transmission. Chromosomal drive typically functions in asymmetric female meiosis, while gene drive is normally postmeiotic and typically found in males. Using single molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Zea mays ssp. mexicana), that depends on RNA interference (RNAi). 22nt small RNAs from a non-coding RNA hairpin in mexicana depend on Dicer-Like 2 (Dcl2) and target Teosinte Drive Responder 1 (Tdr1), which encodes a lipase required for pollen viability. Dcl2, Tdr1, and the hairpin are in tight pseudolinkage on chromosome 5, but only when transmitted through the male. Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize. A survey of maize landraces and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least 3 chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive likely played a major role in maize domestication and evolution, and offers an explanation for the widespread abundance of "self" small RNAs in the germlines of plants and animals.Competing Interest StatementThe authors have declared no competing interest.

26619
N. Wybouw, E. Van Reempts, J. Zarka, F. Zélé and D. Bonte,  Heredity,  2023-07-13 08:18:54.
Maternally transmitted symbionts such as Wolbachia can alter sex allocation in haplodiploid arthropods. By biasing population sex ratios towards females, these changes in sex allocation may facilitate the spread of symbionts. In contrast to symbiont-induced cytoplasmic incompatibility (CI), the mechanisms that underpin sex allocation distortion remain poorly understood. Using a nuclear genotype reference panel of the haplodiploid mite Tetranychus urticae and a single Wolbachia variant that is able to simultaneously induce sex allocation distortion and CI, we unraveled the mechanistic basis of Wolbachia-mediated sex allocation distortion. Host genotype was an important determinant for the strength of sex allocation distortion. We further show that sex allocation distortion by Wolbachia in haplodiploid mites is driven by increasing egg size, hereby promoting egg fertilization. This change in reproductive physiology was also coupled to increased male and female adult size. Our results echo previous work on Cardinium symbionts, suggesting that sex allocation distortion by regulating host investment in egg size is a common strategy among symbionts that infect haplodiploids. To better understand the relevance that sex allocation distortion may have for the spread of Wolbachia in natural haplodiploid populations, we parametrized a model based on generated phenotypic data. Our simulations show that empirically derived levels of sex allocation distortion can be sufficient to remove invasion thresholds, allowing CI to drive the spread of Wolbachia independently of the initial infection frequency. Our findings help elucidate the mechanisms that underlie the widespread occurrence of symbionts in haplodiploid arthropods and the evolution of sex allocation.

Fighting the battle against evolution: designing genetically modified organisms for evolutionary stability

28008
M. Arbel-Groissman, I. Menuhin-Gruman, D. Naki, S. Bergman and T. Tuller,  Trends in Biotechnology,  2023-07-12 06:48:15.
Synthetic biology has made significant progress in many areas, but a major challenge that has received limited attention is the evolutionary stability of synthetic constructs made of heterologous genes. The expression of these constructs in microorganisms, that is, production of proteins that are not necessary for the organism, is a metabolic burden, leading to a decrease in relative fitness and make the synthetic constructs unstable over time. This is a significant concern for the synthetic biology community, particularly when it comes to bringing this technology out of the laboratory. In this review, we discuss the issue of evolutionary stability in synthetic biology and review the available tools to address this challenge

Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii

26580
R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James,  Proceedings of the National Academy of Sciences,  120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.

The cellular lives of Wolbachia

26608
J. Porter and W. Sullivan,  Nature Reviews Microbiology,  2023-07-10 13:14:07.
Wolbachia are successful Gram-negative bacterial endosymbionts, globally infecting a large fraction of arthropod species and filarial nematodes. Efficient vertical transmission, the capacity for horizontal transmission, manipulation of host reproduction and enhancement of host fitness can promote the spread both within and between species. Wolbachia are abundant and can occupy extraordinary diverse and evolutionary distant host species, suggesting that they have evolved to engage and manipulate highly conserved core cellular processes. Here, we review recent studies identifying Wolbachia–host interactions at the molecular and cellular levels. We explore how Wolbachia interact with a wide array of host cytoplasmic and nuclear components in order to thrive in a diversity of cell types and cellular environments. This endosymbiont has also evolved the ability to precisely target and manipulate specific phases of the host cell cycle. The remarkable diversity of cellular interactions distinguishes Wolbachia from other endosymbionts and is largely responsible for facilitating its global propagation through host populations. Finally, we describe how insights into Wolbachia–host cellular interactions have led to promising applications in controlling insect-borne and filarial nematode-based diseases.

Estimating mosquito abundance and population suppression in an incompatible insect technique study

26901
L. Griffin, D. Pagendam, C. Drovandi, B. Trewin and N. W. Beebe,  Journal of Applied Ecology,  2023-07-10 10:53:08.
Our model can provide valuable insights that can shape decision support systems in sterile insect technique and incompatible insect technique programmes operating over large geographical scales. The model helps determine how many sterile/incompatible insects should be released over time and how population control is progressing (via use of counterfactual scenarios). These outcomes are achieved because the model provides estimates of wild-type populations over time, even when there has been no differentiation between sterile/incompatible and wild-type insects caught in trap

Genome and Transcriptome Analyses Facilitate Genetic Control of Wohlfahrtia magnifica, a Myiasis-Causing Flesh Fly

27427
Z. Jia, S. Hasi, D. Zhan, B. Hou, C. Vogl and P. A. Burger,  Insects,  14. 2023-07-10 08:53:12.
Myiasis caused by Wohlfahrtia magnifica is a widespread parasitic infestation in mammals. The infested host suffers from damage as the developing larvae feed on its tissues. For the control of myiasis infestation, genetic methods have been shown to be effective and promising as an alternative to insecticides. Combining genome, isoform sequencing (Iso-Seq), and RNA sequencing (RNA-seq) data, we isolated and characterized two sex-determination genes, W. magnifica transformer (Wmtra) and W. magnifica transformer2 (Wmtra2), whose orthologs in a number of insect pests have been utilized to develop genetic control approaches. Wmtra transcripts are sex-specifically spliced; only the female transcript encodes a full-length functional protein, while the male transcript encodes a truncated and non-functional polypeptide due to the presence of the male-specific exon containing multiple in-frame stop codons. The existence of five predicted TRA/TRA2 binding sites in the male-specific exon and the surrounding intron of Wmtra, as well as the presence of an RNA-recognition motif in WmTRA2 may suggest the auto-regulation of Wmtra by its own protein interacting with WmTRA2. This results in the skipping of the male-specific exon and translation of the full-length functional protein only in females. Our comparative study in dipteran species showed that both the WmTRA and WmTRA2 proteins exhibit a high degree of similarity to their orthologs in the myiasis-causing blow flies. Additionally, transcriptome profiling performed between adult females and adult males reported 657 upregulated and 365 downregulated genes. Functional analysis showed that among upregulated genes those related to meiosis and mitosis Gene Ontology (GO) terms were enriched, while, among downregulated genes, those related to muscle cell development and aerobic metabolic processes were enriched. Among the female-biased gene set, we detected five candidate genes, vasa (vas), nanos (nanos), bicoid (bcd), Bicaudal C (BicC), and innexin5 (inx5). The promoters of these genes may be able to upregulate Cas9 expression in the germline in Cas9-based homing gene drive systems as established in some flies and mosquitoes. The isolation and characterization of these genes is an important step toward the development of genetic control programs against W. magnifica infestation.

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