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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Gene Editing and Genetic Control of Hemipteran Pests: Progress, Challenges and Perspectives

22757
I. D. Pacheco, L. L. Walling and P. W. Atkinson,  Frontiers in Bioengineering and Biotechnology,  10. 2022-06-07 08:02:11.
The origin of the order Hemiptera can be traced to the late Permian Period more than 230 MYA, well before the origin of flowering plants 100 MY later in during the Cretaceous period. Hemipteran species consume their liquid diets using a sucking proboscis; for phytophagous hemipterans their mouthparts (stylets) are elegant structures that enable voracious feeding from plant xylem or phloem. This adaptation has resulted in some hemipteran species becoming globally significant pests of agriculture resulting in significant annual crop losses. Due to the reliance on chemical insecticides for the control of insect pests in agricultural settings, many hemipteran pests have evolved resistance to insecticides resulting in an urgent need to develop new, species-specific and environmentally friendly methods of pest control. The rapid advances in CRISPR/Cas9 technologies in model insects such as Drosophila melanogaster, Tribolium castaneum, Bombyx mori, and Aedes aegypti has spurred a new round of innovative genetic control strategies in the Diptera and Lepidoptera and an increased interest in assessing genetic control technologies for the Hemiptera. Genetic control approaches in the Hemiptera have, to date, been largely overlooked due to the problems of introducing genetic material into the germline of these insects. The high frequency of CRISPR-mediated mutagenesis in model insect species suggest that, if the delivery problem for Hemiptera could be solved, then gene editing in the Hemiptera might be quickly achieved. Significant advances in CRISPR/Cas9 editing have been realized in nine species of Hemiptera over the past 4 years. Here we review progress in the Hemiptera and discuss the challenges and opportunities for extending contemporary genetic control strategies into species in this agriculturally important insect orderr.

Beware the Unknown: Views on Genetic Technology in Conservation

H. G. W. Dixson, J. Balanovic, F. Medvecky, E. D. Edwards and E. A. MacDonald,  Narrative Inquiry in Bioethics,  12. 2022-06-06 08:59:56.
Artificial Gene Drive (GD) may offer a number of transformative impacts on society. Despite potential usage in the area of conservation, GD remains largely unfamiliar to the public and little is known about their views. In our study, participants from New Zealand were placed in groups based upon one of four worldviews. They had a brief free word association session before considering a concise, technical definition of GD and were asked to discuss their views. Overall, discussions made use of narrative devices that expressed caution and concern around large-scale technological intervention with the natural world. However, specific worldviews presented unique themes. While fears of human overstep causing uncontrollable feedback across wild species and environments were universally present, this differed according to the group's worldview. We conclude that conversations on such technologies, especially those relating to gene modification, provide insight into deep-rooted social, cultural and even metaphysical concerns that transcend the technology's stated purpose.

Establishment of Wolbachia infection in Aedes aegypti from Pakistan via embryonic microinjection and semi-field evaluation of general fitness of resultant mosquito population

22856
M. S. Sarwar, N. Jahan, A. Ali, H. K. Yousaf and I. Munzoor,  Parasites and Vectors,  15:191. 2022-06-06 08:36:19.
BACKGROUND: Dengue is a mosquito-borne viral disease that is mainly spread by Aedes aegypti. It is prevalent on five continents, predominantly in tropical and sub-tropical zones across the world. Wolbachia bacteria have been extensively used in vector control strategies worldwide. The focus of the current study was to obtain a natural population of Ae. aegypti harbouring Wolbachia and to determine the impact of this bacteria on the new host in a semi-field environment. METHODS: Wolbachia-infected Aedes albopictus was collected from the city of Lahore, Punjab, Pakistan, and Wolbachia were successfully introduced into laboratory-reared Ae. aegypti via embryonic microinjection. The stable vertical transmission of wAlbB in the host population was observed for eight generations, and the impact of Wolbachia on the general fitness of the host was evaluated in semi-field conditions. RESULTS: In the laboratory and semi-field experiments, wAlbB Wolbachia presented a strong cytoplasmic incompatibility (CI) effect, evidenced as zero egg hatching, in crosses between Wolbachia-infected males and wild (uninfected) females of Ae. aegypti. Wolbachia infection had no noticeable impact on the general fitness (P > 0.05), fecundity, body size (females and males) and mating competitiveness of the new host, Ae. aegypti. However, there was a significant decrease in female fertility (egg hatch) (P < 0.001). In addition, under starvation conditions, there was a remarkable decrease (P < 0.0001) in the life span of Wolbachia-infected females compared to uninfected females (4 vs. > 5 days, respectively). CONCLUSIONS: Wolbachia strain wAlbB has a great potential to control the dengue vector in Ae. aegypti populations by producing 100% CI with a limited burden on its host in natural field conditions. This strain can be used as a biological tool against vector-borne diseases.

Non-Mendelian segregation and transmission drive of B chromosomes

22725
J. P. M. Camacho,  Chromosome Research,  2022-06-03 07:58:27.
Selfish genetic elements (SGE) get a transmission advantage (drive) thanks to their non-Mendelian inheritance. Here I identify eight steps during the reproductive cycle that can be subverted by SGEs to thrive in natural populations. Even though only three steps occur during meiosis, most cases of segregation distortion are considered “meiotic drive sensu lato.” As this is a source of unnecessary contradictions, I suggest always using the term “transmission ratio distortion” (TRD). Chromosomal SGEs (e.g., B chromosomes) exhibit almost all types of TRD. In plants, the best-studied type of TRD for B chromosomes occurs post-meiotically during male gametophyte maturation. However, in animals, the two main types are pre-meiotic and meiotic TRDs, in all cases associated with gonotaxis (i.e., a preference of B chromosomes for germ cells). Frequently, TRD drivers in genic SGEs (e.g., t-alleles and segregation distorters in Drosophila) are paralogous copies of genes from the standard genome, whereas their targets can be other genes or satellite DNA (satDNA). As B chromosomes are often rich in satDNA and contain paralogous copies of A chromosome genes, perhaps their drive mechanisms are similar to those of genic SGEs. So far, the only association between a B chromosome gene and TRD is the gene haplodizer in Nasonia vitripennis. The discovery of B-genes controlling B-drive in other species does not appear to be far off, but experimental crosses will be needed to simultaneously test the TRD of a given B chromosome and the expression of its genes.

The maize abnormal chromosome 10 meiotic drive haplotype: a review

22690
R. K. Dawe,  Chromosome Research,  2022-06-02 14:35:18.
The maize abnormal chromosome 10 (Ab10) haplotype encodes a meiotic drive system that converts heterochromatic knobs into centromere-like bodies that are preferentially segregated through female meiosis. Ab10 was first described in the 1940s and has been intensively studied. Here I provide a comprehensive review of the literature, starting from the discovery of knobs and Ab10, preceding through the classic literature, and finishing with molecular structure and mechanisms. The defining features of the Ab10 haplotype are its two specialized kinesins, Kinesin driver and TR-1 kinesin, that activate neocentromeres at knobs containing different classes of the tandem repeat. In most Ab10 haplotypes, the two kinesin/knob systems cooperate to promote maximum meiotic drive. However, recent interpretations suggest that each kinesin/knob system can function as an independent meiotic driver and that in some cases they compete with each other. Ab10 is present at low frequencies throughout the genus Zea and has significantly expanded genome size by promoting the formation of knobs throughout the genome.

Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae

22689
D. A. Ellis, G. Avraam, A. Hoermann, C. A. S. Wyer, Y. X. Ong, G. K. Christophides and N. Windbichler,  PLOS Genetics,  18:e1010244. 2022-06-02 14:26:57.
Author summary Gene drive is a method that allows the genetic modification of entire populations of harmful organisms. Their application to tackle invasive species, agricultural pests or insect disease vectors has been suggested. For example, they could reduce the capacity of malaria mosquitoes to transmit this deadly disease to humans by producing effector molecules inhibiting the development of the Plasmodium parasite in the mosquito vector. We describe a strategy to modularize and test multiple transgenes destined for release, and to introduce only the minimal set of modifications needed into a mosquito population. We show how some elements, once no longer needed, can be made to self-eliminate from populations and we also study how several independent gene drive traits, located in different parts of the genome, can interact and propagate at the level of mosquito cage populations.

Modifying mosquitoes to suppress disease transmission: Is the long wait over?

22854
J. R. Powell,  Genetics,  2022-06-02 08:31:17.
For more than 50 years it has been a dream of medical entomologists and public health workers to control diseases like malaria and dengue fever by modifying, through genetics and other methods, the arthropods that transmit them to humans. A brief synopsis of the history of these efforts as applied to mosquitoes is presented; none proved to be effective in reducing disease prevalence. Only in the last few years have novel approaches been developed or proposed that indicate the long wait may be over. Three recent developments are particularly promising: CRISPR-Cas9 driven genetic modification, shifting naturally occurring allele frequencies, and microbe-based modifications. The last is the furthest along in implementation. Dengue fever incidence has been reduced between 40% and 96% in 4 different regions of the world where Wolbachia-infected Aedes aegypti have been established in the field. It is not yet clear how sustainable such control programs will prove to be, but there is good reason for optimism. In light of this, the time is ripe for reinvigorated research on vectors, especially genetics. Vector-borne diseases primarily affect under-developed countries and thus have not received the attention they deserve from wealthier countries with well-developed and funded biomedical research establishments.

A meiotic driver alters sperm form and function in house mice: a possible example of spite

22697
L. Winkler and A. K. Lindholm,  Chromosome Research,  2022-06-01 14:48:38.
The ability to subvert independent assortment of chromosomes is found in many meiotic drivers, such as the t haplotype in house mice Mus musculus, in which the t-bearing chromosomal homolog is preferentially transmitted to offspring. This is explained by a poison-antidote system, in which developing + and t sperm in testes of + /t males are exposed to 'poison' coded by t loci, from which t sperm are protected, allowing t sperm an overwhelming fertilisation advantage in monogamous matings. This system is thought to result in poorly and normally motile sperm subpopulations within + /t sperm, leaving t sperm unharmed. Conversely, we found that the fastest quartile of sperm from + /t males swam more slowly, both forwards and along their travel path, and had reduced straightness and linearity, compared to the fastest quartile of + / + sperm. Moreover, sperm from + /t males had shorter tails and narrower heads than + / + sperm, and these morphological differences covaried with motility differences. Finally, + /t traits did not show evidence of bimodal distributions. We conclude that the t haplotype drive results in lasting damage to the motility of both + and t developing sperm, although previous studies indicate that + must be more harmed than t sperm. This damage to all sperm may explain the low success of + /t males in sperm competition with + / + males, seen in earlier studies. We propose that the harm the t causes to itself could be termed 'spiteful', which may also be common to other gamete-harming meiotic drive systems.

Wolbachia interacts with the microbiome to shape fitness-associated traits during seasonal adaptation in Drosophila melanogaster

22693
L. P. Henry, M. Fernandez, S. Wolf and J. Ayroles,  bioRxiv,  2022.05.31.494239. 2022-06-01 14:39:02.
The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the evolutionary effects of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal adaptation with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, interactions between Wolbachia and the microbiome contributed to fitness-associated traits. Wolbachia often exerted negative fitness effects on hosts, and the microbiome modulated these effects. Our work supports recent theoretical advances suggesting that hosts in temporally fluctuating environments benefit from flexible microbial associations with low transmission fidelity--specifically when changes in the microbiome can better enable host phenotypes to match environment change. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes and the utility of Wolbachia in combating vector-borne disease.Competing Interest StatementThe authors have declared no competing interest.

Exploring value change

25095
T. E. de Wildt and V. J. Schweizer,  Prometheus,  38. 2022-06-01 10:02:19.
This article aims to explore the use of cross-impact balances (CIB) to identify scenarios of value change. The possibility of value change has received little attention in the literature on value-sensitive design (VSD). Examples of value change include the emergence of new values and changes in the relative importance of values. Value change could lead to a mismatch between values embedded in technology and the way they are currently considered in society. Such a mismatch could result in a lack of acceptability of technologies, increasing social tensions and injustices. However, methods to study value change in the VSD literature are rare. CIB is a scenario tool that can study systems characterized by feedback loops that are hard to describe mathematically. This is often the case when aiming to define values and their relationships. We demonstrate the use of CIB to identify scenarios of value change using two cases: digital voice assistants and gene drive organisms. Our findings show that CIB is helpful in building scenarios of value change, even in instances where the operationalization of values is complex. CIB also helps us to understand the mechanisms of value change and evaluate when such mechanisms occur. Finally, we find that CIB is particularly useful for social learning and explanatory modelling. CIB can therefore contribute to the design of value-sensitive technologies.

Modeling the impact of genetically modified male mosquitoes in the spatial population dynamics of Aedes aegypti

23212
M. R. da Silva, P. H. G. Lugão, F. Prezoto and G. Chapiro,  Scientific Reports,  12:9112. 2022-06-01 06:29:36.
The mosquito Aedes aegypti is the primary vector of diseases such as dengue, Zika, chikungunya, and yellow fever. Improving control techniques requires a better understanding of the mosquito’s life cycle, including spatial population dynamics in endemic regions. One of the most promising techniques consists of introducing genetically modified male mosquitoes. Several models proposed to describe this technique present mathematical issues or rely on numerous parameters, making their application challenging to real-world situations. We propose a model describing the spatial population dynamics of the Aedes aegypti in the presence of genetically modified males. This model presents some mathematical improvements compared to the literature allowing deeper mathematical analysis. Moreover, this model relies on few parameters, which we show how to obtain or estimate from the literature. Through numerical simulations, we investigate the impacts of environmental heterogeneity, the periodicity of genetically modified male releases, and released genetically modified males quantity on the population dynamics of Aedes aegypti. The main results point to that the successful application of this vector control technique relies on releasing more than a critical amount of modified males with a frequency exceeding a specific critical value.

Combined Trojan Y Chromosome Strategy and Sterile Insect Technique to Eliminate Mosquitoes: Modelling and Analysis

23051
J. Lyu, M. Gu, S. Wang and K. Cheng,  Mathematical Problems in Engineering,  2022:2373350. 2022-05-27 15:09:13.
Sterile insect technique has been successfully applied in the control of agricultural pests; however, it has a limited ability to control mosquitoes. A promising alternative approach is the Trojan Y Chromosome strategy, which works by manipulating the sex ratio of a population through the introduction of YY supermales that guarantee male offspring. To take the advantages of both approaches, a combined Trojan Y chromosome strategy and sterile insect technique (TYC-SIT) strategy considering intraspecies competition is modeled. The pure TYC method is compared with the pure SIT method by cancelling one-state variable. The dynamical analysis leads to results on both local and global stabilities of this combined TYC-SIT model. Optimal control analysis is also implemented to investigate the optimal mechanisms for extinction of mosquitoes. In particular, the numerical results affirm that the combined TYC-SIT enables near elimination of mosquitoes and works better than the pure TYC or pure SIT method. These conclusions have great significance for species controls with an XX-XY sex determinism system or ZZ-ZW system.

Optimization of Aedes albopictus (Diptera: Culicidae) Mass Rearing through Cost-Effective Larval Feeding

22626
M. Kavran, A. Puggioli, S. Šiljegović, D. Čanadžić, N. Laćarac, M. Rakita, A. Ignjatović Ćupina, F. Balestrino, D. Petrić and R. Bellini,  Insects,  13. 2022-05-26 07:11:26.
Aedes (Stegomyia) albopictus (Skuse, 1895) is an invasive important medical and veterinary pest species. The sterile insect technique (SIT) involves the mass rearing of males, and their sterilization and release into the habitat to compete with wild males. Our research objective was to compare the effectiveness of three larval diet recipes (IAEA-BY, BCWPRL, and MIX-14) in the laboratory rearing of Ae. albopictus males to evaluate the available economical feeding alternatives. The separation of sexes was done in the pupal stage by sieving. Reared males were tested for flight capacity and longevity. The application of the BCWPRL diet resulted in a higher portion of sieved male pupae than females, but the development of males was the slowest, and the number of obtained males (pupae and adults) was lower compared to the other two diets. The adult mean survival time was the highest in males fed with MIX-14 and the lowest in males fed with IAEA-BY. Males fed by IAEA-BY also demonstrated higher initial mortality in the adult stage. The diets BCWPRL and MIX-14 are economically more convenient than IAEA-BY (2.28 and 5.30 times cheaper, respectively). The cheapest diet, MIX-14, might represent a candidate for replacing the effective but still expensive IAEA-BY larval diet, providing lower costs of sterile male production.

Reply to: Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes

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J. E. Crawford, K. C. Hopkins, A. Buchman, T. Zha, P. Howell, E. Kakani, J. R. Ohm, N. Snoad, L. Upson, J. Holeman, P. Massaro, S. L. Dobson, F. S. Mulligan and B. J. White,  Nature Biotechnology,  2022-05-26 06:34:15.
We appreciate the comments from Bouyer et al. under their mandate as a United Nations agency program (‘to promote the safe and appropriate use of nuclear techniques and related technologies in food and agriculture’) on our paper1 . The centuries-old fight against mosquito-borne disease has entered a new phase that is both exciting and fast-moving. Many promising technologies and techniques have been developed in the past 2 decades, including mosquito colonies stably infected with Wolbachia2 mosquitoes3,4, a CRISPR–Cas9-based gene drive5 nations of these techniques with older approaches (that is, irradiated Wolbachia releases6,7 , genetically modified sterile and even combi). In a world where more than half of all humans are at risk of contracting mosquito-borne diseases across a range of economic and geographic landscapes, we think that an array of tools will be needed to turn the tide against the massive public health burden of these diseases.

Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes

22641
J. Bouyer, H. Maiga and M. J. B. Vreysen,  Nature Biotechnology,  2022-05-26 06:27:58.
A paper by Crawford et al.1 titled ‘Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations’ reports a mosquito control suppression trial carried out from2017 to 2018 in Fresco Country, California, USA1 . Between 7.5 million and 14.4 million Wolbachia-infected male mosquitoes were released during the study, which achieved suppression rates of 69% and 95%, respectively. Although the work provided important insights for future Aedes genetic control programs—particularly the information on the immigration of fertile females into release areas—the paper contains several omissions and errors. Below, we discuss how these relate to three main areas: regulatory oversight, entomological efficiency and, finally, cost efficiency.

Recommendations for environmental risk assessment of gene drive applications for malaria vector control

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J. B. Connolly, J. D. Mumford, D. C. M. Glandorf, S. Hartley, O. T. Lewis, S. W. Evans, G. Turner, C. Beech, N. Sykes, M. B. Coulibaly, J. Romeis, J. L. Teem, W. Tonui, B. Lovett, A. Mankad, A. Mnzava, S. Fuchs, T. D. Hackett, W. G. Landis, J. M. Marshall,  Malar J,  21:152. 2022-05-25 09:36:02.
Building on an exercise that identified potential harms from simulated investigational releases of a population suppression gene drive for malaria vector control, a series of online workshops identified nine recommendations to advance future environmental risk assessment of gene drive applications.

Perplexing dynamics of Wolbachia proteins for cytoplasmic incompatibility

22582
T. Harumoto and T. Fukatsu,  PLOS Biology,  20:e3001644. 2022-05-25 09:23:59.
The mechanism of symbiont-induced cytoplasmic incompatibility has been a long-lasting mystery. This Primer explores a new study on Wolbachia’s Cif proteins in PLOS Biology that provides supportive evidence for the “Host-Modification Model,” although the alternative “Toxin-Antidote Model” is still in the running.

A nickase Cas9 gene-drive system promotes super-Mendelian inheritance in Drosophila

22584
V. L. Del Amo, S. S. Juste and V. M. Gantz,  Cell Rep,  39:110843. 2022-05-24 09:32:51.
CRISPR-based gene-drives have been proposed for managing insect populations, including disease-transmitting mosquitoes, due to their ability to bias their inheritance toward super-Mendelian rates (>50%). Current technologies use a Cas9 that introduces DNA double-strand breaks into the opposing wild-type allele to replace it with a copy of the gene-drive allele via DNA homology-directed repair. However, the use of different Cas9 versions is unexplored, and alternative approaches could increase the available toolkit for gene-drive designs. Here, we report a gene-drive that relies on Cas9 nickases that generate staggered paired nicks in DNA to propagate the engineered gene-drive cassette. We show that generating 5' overhangs in the system yields efficient allelic conversion. The nickase gene-drive arrangement produces large, stereotyped deletions that are advantageous to eliminate viable animals carrying small mutations when targeting essential genes. Our nickase approach should expand the repertoire for gene-drive arrangements aimed at applications in mosquitoes and beyond.

The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility

22570
R. Kaur, B. A. Leigh, I. T. Ritchie and S. R. Bordenstein,  PLOS Biology,  20:e3001584. 2022-05-24 08:55:13.
In Drosophila melanogaster, germline expression of the Wolbachia proteins CifA and CifB causes cytoplasmic incompatibility, but how this impairs male reproduction remains unclear. This study shows how Cif proteins encoded by the endosymbiont prophage invade the fly’s gametic nuclei and modify the histone-protamine transition of spermatogenesis.

Wolbachia 16S rRNA haplotypes detected in wild Anopheles stephensi in eastern Ethiopia

22568
E. Waymire, S. Duddu, S. Yared, D. Getachew, D. Dengela, S. R. Bordenstein, M. Balkew, S. Zohdy, S. R. Irish and T. E. Carter,  Parasites and Vectors,  15:178. 2022-05-24 08:50:15.
About two out of three Ethiopians are at risk of malaria, a disease caused by the parasites Plasmodium falciparum and Plasmodium vivax. Anopheles stephensi, an invasive vector typically found in South Asia and the Middle East, was recently found to be distributed across eastern and central Ethiopia and is capable of transmitting both P. falciparum and P. vivax. The detection of this vector in the Horn of Africa (HOA) coupled with widespread insecticide resistance requires that new methods of vector control be investigated in order to control the spread of malaria. Wolbachia, a naturally occurring endosymbiotic bacterium of mosquitoes, has been identified as a potential vector control tool that can be explored for the control of malaria transmission. Wolbachia could be used to control the mosquito population through suppression or potentially decrease malaria transmission through population replacement. However, the presence of Wolbachia in wild An. stephensi in eastern Ethiopia is unknown. This study aimed to identify the presence and diversity of Wolbachia in An. stephensi across eastern Ethiopia.

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