The sex-specific factor SOA controls dosage compensation in Anopheles mosquitoes

Agata Izabela Kalita, Eric Marois, Magdalena Kozielska, Franz J. Weissing, Etienne Jaouen, Martin M. Möckel, Frank Rühle, Falk Butter, M. Felicia Basilicata and Claudia Isabelle Keller Valsecchi ()
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Agata Izabela Kalita: Institute of Molecular Biology (IMB)
Eric Marois: Université de Strasbourg
Magdalena Kozielska: University of Groningen
Franz J. Weissing: University of Groningen
Etienne Jaouen: Université de Strasbourg
Martin M. Möckel: Institute of Molecular Biology (IMB)
Frank Rühle: Institute of Molecular Biology (IMB)
Falk Butter: Institute of Molecular Biology (IMB)
M. Felicia Basilicata: Institute of Molecular Biology (IMB)
Claudia Isabelle Keller Valsecchi: Institute of Molecular Biology (IMB)

Nature, 2023, vol. 623, issue 7985, 175-182

Abstract: Abstract The Anopheles mosquito is one of thousands of species in which sex differences play a central part in their biology, as only females need a blood meal to produce eggs. Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex chromosomal genes. However, because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved1. Here we report the discovery of a previously uncharacterized gene (sex chromosome activation (SOA)) as a master regulator of DC in the malaria mosquito Anopheles gambiae. Sex-specific alternative splicing prevents functional SOA protein expression in females. The male isoform encodes a DNA-binding protein that binds the promoters of active X chromosomal genes. Expressing male SOA is sufficient to induce DC in female cells. Male mosquitoes lacking SOA or female mosquitoes ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analyses of a DC master regulator in a non-model organism elucidates the evolutionary steps that lead to the establishment of a chromosome-specific fine-tuning mechanism.

Date: 2023
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DOI: 10.1038/s41586-023-06641-0

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