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

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.

Y chromosome shredding in Anopheles gambiae: Insight into the cellular dynamics of a novel synthetic sex ratio distorter

“…merus, are karyotypically distinct [14][15][16]. A number of genomic and functional studies have been conducted on sex chromosomes and sex determination in the main malaria vector Anopheles gambiae [17][18][19][20][21][22][23][24][25]. This species has a pair of fully differentiated heteromorphic X and Y chromosomes with some level of sequence similarity, mostly involving satellite DNA.…”

Dynamics of X chromosome hyper-expression and inactivation in male tissues during stick insect development

“…In the fly, upregulation of the single X in male somatic tissues is partially mediated by the male-specific lethal (MSL) protein complex, which promotes the transcription of X-linked genes via H4K16 hyperacetylation, with apparently no chromosome-wide modification of X expression in females [17,18]. In the mosquito, dosage compensation is regulated via sex-specific alternative splicing of a gene referred to as "sex chromosome activation (SOA)" or "007", but how this gene activates expression on the male X remains unknown [19,20].…”