High-resolution transcriptional profiling of Anopheles gambiae spermatogenesis reveals mechanisms of sex chromosome regulation

Taxiarchi, Chrysanthi; Kranjc, Nace; Kriezis, Antonios; Kyrou, Kyros; Bernardini, Federica; Russell, Steven; Nolan, Tony; Crisanti, Andrea; Galizi, Roberto

doi:10.1038/s41598-019-51181-1

Cited by 32 publications

(46 citation statements)

References 69 publications

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“…However, attempts to convert synthetic sex-ratio distorters into Y-chromosome drives have been unsuccessful so far. In most insect species, including A. gambiae , the sex chromosomes are transcriptionally shut down during gametogenesis, a process known as meiotic sex-chromosome inactivation 15 , 16 , which prevents the transcription of X-shredding nucleases if they are inserted into the Y chromosome (personal observation, A.C. and R.G.).…”

Section: Mainmentioning

confidence: 99%

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

et al. 2020

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ex-chromosome drivers are genetic elements that interfere with chromosome segregation during meiosis and are over-represented in progeny 1. In heterogametic sex, they cause an unbalanced male-to-female ratio among offspring, which can potentially lead to population suppression or extinction. Relatively few sex-chromosome drives have been characterized, most likely because they produce an evolutionary conflict with the rest of the genome that selects for autosomal suppressors or resistant sex chromosomes 2,3. Mathematical modeling predicts that a driving sex distorter will spread in a population and, in the absence of resistance, cause eventual collapse 4,5. Population collapse using natural sex-chromosome drives has been reported in laboratory colonies of Drosophila 6,7. In the field, a population crash of the species Drosophila neotestacea was detected in Washington State due to a natural X-chromosome distorter that produced a female-only population 8. Therefore, sex-distorter drives could conceivably be harnessed for invasive pest or vector control 9,10. Although Y drives are less common than X drives, they have been described in Aedes aegypti and Culex pipiens mosquitoes 11,12. Y drives are particularly attractive for mosquito vector control because they can progressively reduce the number of females and hence disease transmission as they spread. In addition, Y drives are likely to be more effective than X drives because they can increase at a greater rate the fraction of heterogametic driving individuals 3-5. Synthetic sex distorters have been generated in A. gambiae mosquitoes by using site-specific nucleases such as I-PpoI or CRISPR-Cas9, which cleave conserved repeated sequences in the mosquito ribosomal DNA gene cluster located exclusively on the X chromosome 13,14. These nucleases, when expressed during spermatozoa development, selectively cleave the X chromosome, thereby favoring the production of Y-bearing gametes and causing a 95% male bias in the progeny 13,14. However, attempts to convert synthetic sex-ratio distorters into Y-chromosome drives have been unsuccessful so far. In most insect species, including A. gambiae, the sex chromosomes are transcriptionally shut down during gametogenesis, a process known as meiotic sex-chromosome inactivation 15,16 , which prevents the transcription of X-shredding nucleases if they are inserted into the Y chromosome (personal observation, A.C. and R.G.). Recently, a gene drive that targeted the dsx gene reached 100% frequency in 7-11 generations and crashed a caged population of 600 mosquitoes without inducing resistance 17. We hypothesized that it might be possible to circumvent meiotic sex-chromosome inactivation by developing an autosomal male-biased sex distorter and coupling sex-ratio distortion with drive. This could result in a quicker impact on disease transmission and a synergistic effect (robustness) between the sex distorter and gene-drive components. Here we report the design and validation of an SDGD to spread the X-chromosome-shredding I-PpoI endonu...

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Section: Mainmentioning

confidence: 99%

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

et al. 2020

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“…Unlike autosomal sex distorters, the X-shredding endonuclease could be inserted on the Y chromosome and, if expressed during spermatogenesis, would result in progeny mainly composed of males that would inherit the transgene [63,83]. However, the transcriptional silencing of sex chromosomes during meiosis has so far impeded the implementation of synthetic Y-linked sex distorters [83], due to meiotic sex chromosome inactivation (MSCI) [84,85], an epigenetic process that is mediated by chromatin condensation of sex chromosomes at the meiotic stage of male gametogenesis [84]. Transcriptional signatures of MSCI were recently shown in the male germline of A. gambiae.…”

Section: Meiotic Drivesmentioning

confidence: 99%

Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors

2021

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Recent advancements in genetic and genome editing research, augmented by the discovery of new molecular tools such as CRISPR, have revolutionised the field of genetic engineering by enabling precise site-specific genome modifications with unprecedented ease. These technologies have found a vast range of applications, including the development of novel methods for the control of vector and pest insects. According to their genetic makeup and engineering, these tools can be tuned to impose different grades of impact on the targeted populations. Here, we review some of the most recent genetic control innovations under development, describing their molecular mechanisms and performance, highlighting the sustainability potentials of such interventions.

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“…darlingi, albeit the following resources are available: a laboratory-adapted inbred colony for genetic manipulation and testing in the laboratory; annotated genome and, favorable but not essential, a transcriptome for the selection of candidate genes and regulatory sequences for the expression of molecular effectors in the mosquitoes. Ad hoc transcriptomes may be unnecessary in the case orthologous genes may be retrievable from sibling species [157][158][159][160][161]. Successes with An.…”

Section: Challenges Alternatives and Transfer To Neotropical Speciesmentioning

confidence: 99%

Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies

et al. 2020

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In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been made towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to control or eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put into research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the optimization of conventional and development of innovative vector-control tools.

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High-resolution transcriptional profiling of Anopheles gambiae spermatogenesis reveals mechanisms of sex chromosome regulation

Abstract: (Supplementary Fig. S8) confirming that most of the genes required for the late stages are transcribed before meiosis, as previously observed also in other model organisms and human spermatogenesis 24,55,56 .

Cited by 32 publications

References 69 publications

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

Genetic Technologies for Sustainable Management of Insect Pests and Disease Vectors

Vector-Focused Approaches to Curb Malaria Transmission in the Brazilian Amazon: An Overview of Current and Future Challenges and Strategies

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