Nixalone is sufficient to convert femaleAedes aegyptiinto fertile males andmyo-sexis needed for male flight

Aryan, Azadeh; Anderson, Michelle A. E.; Biedler, James K.; Qi, Yumin; Overcash, Justin M.; Naumenko, Anastasia N.; Sharakhova, Maria V.; Mao, Chunhong; Adelman, Zach N.; Tu, Zhijian

doi:10.1073/pnas.2001132117

Cited by 59 publications

(77 citation statements)

References 46 publications

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“…Nix , which encodes a male-determining factor that is necessary and sufficient to drive male-specific development in A. aegypti [ 11 ], overalapped with FAIRE peaks located at the TSS and within an intron of this gene. The myo-sex gene, which is required for A. aegypti male flight [ 1 , 10 ], is associated with eight intronic FAIRE peaks. FAIRE elements associated with these M/m locus genes (Table 3 ) may function as CREs that regulate sex-specific gene expression in A. aegypti .…”

Section: Resultsmentioning

confidence: 99%

PeakMatcher facilitates updated Aedes aegypti embryonic cis-regulatory element map

et al. 2021

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Background The Aedes aegypti mosquito is a threat to human health across the globe. The A. aegypti genome was recently re-sequenced and re-assembled. Due to a combination of long-read PacBio and Hi-C sequencing, the AaegL5 assembly is chromosome complete and significantly improves the assembly in key areas such as the M/m sex-determining locus. Release of the updated genome assembly has precipitated the need to reprocess historical functional genomic data sets, including cis-regulatory element (CRE) maps that had previously been generated for A. aegypti. Results We re-processed and re-analyzed the A. aegypti whole embryo FAIRE seq data to create an updated embryonic CRE map for the AaegL5 genome. We validated that the new CRE map recapitulates key features of the original AaegL3 CRE map. Further, we built on the improved assembly in the M/m locus to analyze overlaps of open chromatin regions with genes. To support the validation, we created a new method (PeakMatcher) for matching peaks from the same experimental data set across genome assemblies. Conclusion Use of PeakMatcher software, which is available publicly under an open-source license, facilitated the release of an updated and validated CRE map, which is available through the NIH GEO. These findings demonstrate that PeakMatcher software will be a useful resource for validation and transferring of previous annotations to updated genome assemblies.

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Section: Resultsmentioning

confidence: 99%

PeakMatcher facilitates updated Aedes aegypti embryonic cis-regulatory element map

et al. 2021

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“…aegypti males are heterogametic (Mm) while the females are homogametic (mm) [41]. Recent studies suggest that the Nix gene has the properties of being the M-locus since it is both 'required and sufficient to initiate male development' [40,42]. Nix resides in a genomic region that is protected from recombination and other functional genes have been identified tightly linked with Nix, with myo-sex being almost exclusively found in males and only sporadically in females, due to recombination [43].…”

Section: Introductionmentioning

confidence: 99%

Irradiation induced inversions suppress recombination between the M locus and morphological markers in Aedes aegypti

et al. 2020

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Background Aedes aegypti is the primary vector of arthropod-borne viruses and one of the most widespread and invasive mosquito species. Due to the lack of efficient specific drugs or vaccination strategies, vector population control methods, such as the sterile insect technique, are receiving renewed interest. However, availability of a reliable genetic sexing strategy is crucial, since there is almost zero tolerance for accidentally released females. Development of genetic sexing strains through classical genetics is hindered by genetic recombination that is not suppressed in males as is the case in many Diptera. Isolation of naturally-occurring or irradiation-induced inversions can enhance the genetic stability of genetic sexing strains developed through genetically linking desirable phenotypes with the male determining region. Results For the induction and isolation of inversions through irradiation, 200 male pupae of the ‘BRA’ wild type strain were irradiated at 30 Gy and 100 isomale lines were set up by crossing with homozygous ‘red-eye’ (re) mutant females. Recombination between re and the M locus and the white (w) gene (causing a recessive white eye phenotype when mutated) and the M locus was tested in 45 and 32 lines, respectively. One inversion (Inv35) reduced recombination between both re and the M locus, and wand the M locus, consistent with the presence of a rather extended inversion between the two morphological mutations, that includes the M locus. Another inversion (Inv5) reduced recombination only between w and the M locus. In search of naturally-occurring, recombination-suppressing inversions, homozygous females from the red eye and the white eye strains were crossed with seventeen and fourteen wild type strains collected worldwide, representing either recently colonized or long-established laboratory populations. Despite evidence of varying frequencies of recombination, no combination led to the elimination or substantial reduction of recombination. Conclusion Inducing inversions through irradiation is a feasible strategy to isolate recombination suppressors either on the M or the m chromosome for Aedes aegypti. Such inversions can be incorporated in genetic sexing strains developed through classical genetics to enhance their genetic stability and support SIT or other approaches that aim to population suppression through male-delivered sterility.

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“…gambiae mosquitoes [11,43], but may also work more broadly [44]. In other species there are other ways to distort the sex ratio [45][46][47], and it would be interesting to model whether these alternatives would be expected to have the same impact as an X-shredder in the context of a double drive. An even simpler way to increase the load would be to add extra gRNAs to the a construct that mutate other female fertility genes [48,49].…”

Section: Discussionmentioning

confidence: 99%

Double drives and private alleles for localised population genetic control

Willis

Burt

2021

Preprint

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Synthetic gene drive constructs could, in principle, provide the basis for highly efficient interventions to control disease vectors and other pest species. This efficiency derives in part from leveraging natural processes of dispersal and gene flow to spread the construct and its impacts from one population to another. However, sometimes (for example, with invasive species) only specific populations are in need of control, and impacts on non-target populations would be undesirable. Many gene drive designs use nucleases that recognise and cleave specific genomic sequences, and one way to restrict their spread would be to exploit sequence differences between target and non-target populations. In this paper we propose and model a series of low threshold double drive designs for population suppression, each consisting of two constructs, one imposing a reproductive load on the population and the other inserted into a differentiated locus and controlling the drive of the first. Simple deterministic, discrete-generation computer simulations are used to assess the alternative designs. We find that the simplest double drive designs are significantly more robust to pre-existing cleavage resistance at the differentiated locus than single drive designs, and that more complex designs incorporating sex ratio distortion can be more efficient still, even allowing for successful control when the differentiated locus is neutral and there is up to 50% pre-existing resistance in the target population. Similar designs can also be used for population replacement, with similar benefits. A population genomic analysis of PAM sites in island and mainland populations of the malaria mosquito Anopheles gambiae indicates that the differentiation needed for our methods to work can exist in nature. Double drives should be considered when efficient but localised population genetic control is needed and there is some genetic differentiation between target and non-target populations.Author summarySome disease vectors, invasive species, and other pests cannot be satisfactorily controlled with existing interventions, and new methods are required. Synthetic gene drive systems that are able to spread though populations because they are inherited at a greater-than-Mendelian rate have the potential to form the basis for new, highly efficient pest control measures. The most efficient such strategies use natural gene flow to spread a construct throughout a species’ range, but if control is only desired in a particular location then these approaches may not be appropriate. As some of the most promising gene drive designs use nucleases to target specific DNA sequences, it ought to be possible to exploit sequence differences between target and non-target populations to restrict the spread and impact of a gene drive. In this paper we propose using two-construct “double drive” designs that exploit pre-existing sequence differences between target and non-target populations. Our approaches maintain the efficiencies associated with only small release rates being needed and can work if the differentiated locus is selectively neutral and if the differentiation is far from complete, and therefore expand the range of options to be considered in developing genetic approaches to control pest species.

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Nixalone is sufficient to convert femaleAedes aegyptiinto fertile males andmyo-sexis needed for male flight

Cited by 59 publications

References 46 publications

PeakMatcher facilitates updated Aedes aegypti embryonic cis-regulatory element map

PeakMatcher facilitates updated Aedes aegypti embryonic cis-regulatory element map

Irradiation induced inversions suppress recombination between the M locus and morphological markers in Aedes aegypti

Double drives and private alleles for localised population genetic control

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