@article{Haber:2024:10.1038/s41467-024-49387-7,
author = {Haber, DA and Arien, Y and Lamdan, LB and Alcalay, Y and Zecharia, C and Krsticevic, F and Yonah, ES and Avraham, RD and Krzywinska, E and Krzywinski, J and Marois, E and Windbichler, N and Papathanos, PA},
doi = {10.1038/s41467-024-49387-7},
journal = {Nat Commun},
title = {Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives.},
url = {http://dx.doi.org/10.1038/s41467-024-49387-7},
volume = {15},
year = {2024}
}

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TY  - JOUR
AB  - Engineered sex ratio distorters (SRDs) have been proposed as a powerful component of genetic control strategies designed to suppress harmful insect pests. Two types of CRISPR-based SRD mechanisms have been proposed: X-shredding, which eliminates X-bearing sperm, and X-poisoning, which eliminates females inheriting disrupted X-chromosomes. These differences can have a profound impact on the population dynamics of SRDs when linked to the Y-chromosome: an X-shredder is invasive, constituting a classical meiotic Y-drive, whereas X-poisoning is self-limiting, unable to invade but also insulated from selection. Here, we establish X-poisoning strains in the malaria vector Anopheles gambiae targeting three X-linked genes during spermatogenesis, resulting in male bias. We find that sex distortion is primarily driven by a loss of X-bearing sperm, with limited evidence for postzygotic lethality of female progeny. By leveraging a Drosophila melanogaster model, we show unambiguously that engineered SRD traits can operate differently in these two insects. Unlike X-shredding, X-poisoning could theoretically operate at early stages of spermatogenesis. We therefore explore premeiotic Cas9 expression to target the mosquito X-chromosome. We find that, by pre-empting the onset of meiotic sex chromosome inactivation, this approach may enable the development of Y-linked SRDs if mutagenesis of spermatogenesis-essential genes is functionally balanced.
AU  - Haber,DA
AU  - Arien,Y
AU  - Lamdan,LB
AU  - Alcalay,Y
AU  - Zecharia,C
AU  - Krsticevic,F
AU  - Yonah,ES
AU  - Avraham,RD
AU  - Krzywinska,E
AU  - Krzywinski,J
AU  - Marois,E
AU  - Windbichler,N
AU  - Papathanos,PA
DO  - 10.1038/s41467-024-49387-7
PY  - 2024///
TI  - Targeting mosquito X-chromosomes reveals complex transmission dynamics of sex ratio distorting gene drives.
T2  - Nat Commun
UR  - http://dx.doi.org/10.1038/s41467-024-49387-7
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38862555
VL  - 15
ER  - 

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