The Potential for a Released Autosomal X-Shredder Becoming a Driving-Y Chromosome and Invasively Suppressing Wild Populations of Malaria Mosquitoes

Yehonatan Alcalay, Silke Fuchs, Roberto Galizi, Federica Bernardini, Roya Elaine Haghighat-Khah, Douglas B. Rusch, Jeffrey R. Adrion, Matthew W. Hahn, Pablo Tortosa, Rachel Rotenberry, Philippos Aris Papathanos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Sex-ratio distorters based on X-chromosome shredding are more efficient than sterile male releases for population suppression. X-shredding is a form of sex distortion that skews spermatogenesis of XY males towards the preferential transmission of Y-bearing gametes, resulting in a higher fraction of sons than daughters. Strains harboring X-shredders on autosomes were first developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against, their frequency in the population declines once releases are halted. However, unintended transfer of X-shredders to the Y-chromosome could produce an invasive meiotic drive element, that benefits from its biased transmission to the predominant male-biased offspring and its effective shielding from female negative selection. Indeed, linkage to the Y-chromosome of an active X-shredder instigated the development of the nuclease-based X-shredding system. Here, we analyze mechanisms whereby an autosomal X-shredder could become unintentionally Y-linked after release by evaluating the stability of an established X-shredder strain that is being considered for release, exploring its potential for remobilization in laboratory and wild-type genomes of An. gambiae and provide data regarding expression on the mosquito Y-chromosome. Our data suggest that an invasive X-shredder resulting from a post-release movement of such autosomal transgenes onto the Y-chromosome is unlikely.

Original languageAmerican English
Article number752253
JournalFrontiers in Bioengineering and Biotechnology
StatePublished - 3 Dec 2021

Bibliographical note

Funding Information:
This study was supported in part by grants from the Bill & Melinda Gates Foundation (Grants INV006610 “Target Malaria Phase II” and INV-004363 “Y chromosome expression for mosquito sex distorting gene drives”). This study was also supported in part by the Italian Ministry of Education, University and Research grant (MIUR—D.M. no. 79 04.02.2014), by the research grant from the United States – Israel Binational Agricultural Research and Development Fund (BARD IS-5180-19) and by the research grant from the Israel Science Foundation (ISF No.2388/19) to P.A.P. SF, FB, RH-K-Employment by Imperial College London in a position which is solely funded through a grant from the Bill &

Publisher Copyright:
Copyright © 2021 Alcalay, Fuchs, Galizi, Bernardini, Haghighat-Khah, Rusch, Adrion, Hahn, Tortosa, Rotenberry and Papathanos.


  • gene drive
  • genetic control
  • malaria
  • risk assessment
  • sex-ratio distortion


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