Yehonatan Alcalay
The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes
Alcalay, Yehonatan; Fuchs, Silke; Galizi, Roberto; Bernardini, Federica; Elaine Haghighat-Khah, Roya; B. Rusch, Douglas; R. Adrion, Jeffrey; W. Hahn, Matthew; Tortosa, Pablo; Aris Papathanos, Philippos
Authors
Silke Fuchs
Roberto Galizi r.galizi@keele.ac.uk
Federica Bernardini
Roya Elaine Haghighat-Khah
Douglas B. Rusch
Jeffrey R. Adrion
Matthew W. Hahn
Pablo Tortosa
Philippos Aris Papathanos
Abstract
Abstract Synthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X-chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I- Ppo I have now been developed in the malaria mosquito Anopheles gambiae , resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding-based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.
Citation
Alcalay, Y., Fuchs, S., Galizi, R., Bernardini, F., Elaine Haghighat-Khah, R., B. Rusch, D., …Aris Papathanos, P. (2019). The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes. https://doi.org/10.1101/860551
Acceptance Date | Nov 30, 2019 |
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Publication Date | Dec 1, 2019 |
Journal | TBC |
Print ISSN | 2373-2873 |
DOI | https://doi.org/10.1101/860551 |
Keywords | autosomal, x-shredder, malaria, mosquitoes |
Publisher URL | https://www.biorxiv.org/content/10.1101/860551v3 |
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