The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes

Alcalay, Y.; Fuchs, S.; Galizi, R.; Bernardini, F.; Haghighat-Khah, R. E.; Rusch, D. B.; Adrion, J. R.; Hahn, M. W.; Tortosa, P.; Papathanos, P. A.

doi:10.1101/860551

bioRxiv · 10.1101/860551

The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes

Alcalay, Y.·Fuchs, S.·Galizi, R.·Bernardini, F.·Haghighat-Khah, R. E.·Rusch, D. B.·Adrion, J. R.·Hahn, M. W.·Tortosa, P.·Papathanos, P. A.

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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-PpoI 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.

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Alcalay, Y., Fuchs, S., Galizi, R., Bernardini, F., Haghighat-Khah, R. E., Rusch, D. B., Adrion, J. R., Hahn, M. W., Tortosa, P., Papathanos, P. A.. 2019-11-30. 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

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