The sex-specific factor SOA establishes X chromosome dosage compensation in Anopheles mosquitos [Mybless-CUTnTag]
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ABSTRACT:
ORGANISM(S): Anopheles gambiae
PROVIDER: GSE233471 | GEO | 2023/07/25
REPOSITORIES: GEO
Similar Datasets
Project description:The Anopheles mosquito is one of thousands of species in which sex differences play a central role in their biology, as only females need a blood meal in order 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, but because the molecular mechanisms providing DC have only been studied in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved. Here, we reveal the DC pathway in the malaria mosquito Anopheles gambiae. We identified SOA, a previously uncharacterized gene, whose expression is sufficient to induce a global upregulation of X-linked genes. Sex-specific alternative splicing prevents the production of a functional SOA protein in females. The male SOA isoform encodes a DNA-binding protein that recognizes the promoters of X chromosomal genes through a CA repeat sequence. Male mosquitos lacking SOA exhibit a chromosome-wide downregulation of the X, which is compatible with viability, but causes a developmental delay. Thus, our molecular analysis of the first DC master regulator in a non-model organism elucidates the evolutionary steps leading to the establishment of a chromosome-specific fine-tuning mechanism.
2023-07-13 | PXD042353 | Pride
Project description:The Anopheles mosquito is one of thousands of species in which sex differences play a central role in their biology, as only females need a blood meal in order 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, but because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved. Here we report the discovery of a previously uncharacterized gene (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 mosquitos ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analysis of the first DC master regulator in a non-model organism elucidates the evolutionary steps leading to the establishment of a chromosome-specific fine-tuning mechanism.
2023-07-25 | GSE233473 | GEO
Project description:The Anopheles mosquito is one of thousands of species in which sex differences play a central role in their biology, as only females need a blood meal in order 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, but because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved. Here we report the discovery of a previously uncharacterized gene (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 mosquitos ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analysis of the first DC master regulator in a non-model organism elucidates the evolutionary steps leading to the establishment of a chromosome-specific fine-tuning mechanism.
2023-07-25 | GSE233472 | GEO
Project description:Differences between males and females are central to the biology of thousands of species across the tree of life. Sex chromosomes play a key role, but despite their their evolutionary diversity, the regulatory mechanisms have been mostly elucidated in the three model species Mammals, D. melanogaster and C. elegans. Here we present the characterization of the first X chromosome dosage compensation (DC) pathway in a non-model organism, the malaria mosquito Anopheles gambiae. In mosquitos, DC corrects the imbalance in gene expression between sexes by approximately two-fold upregulation of male X-linked genes. We have identified SOA, a previously uncharacterized gene, which is specific to Anophelinae and activated concomitantly with the onset of DC. SOA displays sex-specific alternative splicing, where only males express full-length protein. SOA is a DNA-binding protein, specifically localizes to an X chromosome territory and binds promoters of active X-linked genes. Expression of the male, but not female isoform, is sufficient to induce DC. SOA knock-out mosquitos display a male-specific developmental delay, which is associated with a global downregulation of the X chromosome. Thus, SOA is the first DC factor discovered in Anopheles and provides only the fourth DC pathway ever identified to date. Since only females are blood-feeding and able to transmit malaria, identification of this sex-specific pathway is highly relevant and an important progress for malaria control programs.
2023-07-25 | GSE210629 | GEO
Project description:Differences between males and females are central to the biology of thousands of species across the tree of life. Sex chromosomes play a key role, but despite their their evolutionary diversity, the regulatory mechanisms have been mostly elucidated in the three model species Mammals, D. melanogaster and C. elegans. Here we present the characterization of the first X chromosome dosage compensation (DC) pathway in a non-model organism, the malaria mosquito Anopheles gambiae. In mosquitos, DC corrects the imbalance in gene expression between sexes by approximately two-fold upregulation of male X-linked genes. We have identified SOA, a previously uncharacterized gene, which is specific to Anophelinae and activated concomitantly with the onset of DC. SOA displays sex-specific alternative splicing, where only males express full-length protein. SOA is a DNA-binding protein, specifically localizes to an X chromosome territory and binds promoters of active X-linked genes. Expression of the male, but not female isoform, is sufficient to induce DC. SOA knock-out mosquitos display a male-specific developmental delay, which is associated with a global downregulation of the X chromosome. Thus, SOA is the first DC factor discovered in Anopheles and provides only the fourth DC pathway ever identified to date. Since only females are blood-feeding and able to transmit malaria, identification of this sex-specific pathway is highly relevant and an important progress for malaria control programs.
2023-07-25 | GSE210628 | GEO
Project description:Differences between males and females are central to the biology of thousands of species across the tree of life. Sex chromosomes play a key role, but despite their their evolutionary diversity, the regulatory mechanisms have been mostly elucidated in the three model species Mammals, D. melanogaster and C. elegans. Here we present the characterization of the first X chromosome dosage compensation (DC) pathway in a non-model organism, the malaria mosquito Anopheles gambiae. In mosquitos, DC corrects the imbalance in gene expression between sexes by approximately two-fold upregulation of male X-linked genes. We have identified SOA, a previously uncharacterized gene, which is specific to Anophelinae and activated concomitantly with the onset of DC. SOA displays sex-specific alternative splicing, where only males express full-length protein. SOA is a DNA-binding protein, specifically localizes to an X chromosome territory and binds promoters of active X-linked genes. Expression of the male, but not female isoform, is sufficient to induce DC. SOA knock-out mosquitos display a male-specific developmental delay, which is associated with a global downregulation of the X chromosome. Thus, SOA is the first DC factor discovered in Anopheles and provides only the fourth DC pathway ever identified to date. Since only females are blood-feeding and able to transmit malaria, identification of this sex-specific pathway is highly relevant and an important progress for malaria control programs.
2023-07-25 | GSE210627 | GEO
Project description:Differences between males and females are central to the biology of thousands of species across the tree of life. Sex chromosomes play a key role, but despite their their evolutionary diversity, the regulatory mechanisms have been mostly elucidated in the three model species Mammals, D. melanogaster and C. elegans. Here we present the characterization of the first X chromosome dosage compensation (DC) pathway in a non-model organism, the malaria mosquito Anopheles gambiae. In mosquitos, DC corrects the imbalance in gene expression between sexes by approximately two-fold upregulation of male X-linked genes. We have identified SOA, a previously uncharacterized gene, which is specific to Anophelinae and activated concomitantly with the onset of DC. SOA displays sex-specific alternative splicing, where only males express full-length protein. SOA is a DNA-binding protein, specifically localizes to an X chromosome territory and binds promoters of active X-linked genes. Expression of the male, but not female isoform, is sufficient to induce DC. SOA knock-out mosquitos display a male-specific developmental delay, which is associated with a global downregulation of the X chromosome. Thus, SOA is the first DC factor discovered in Anopheles and provides only the fourth DC pathway ever identified to date. Since only females are blood-feeding and able to transmit malaria, identification of this sex-specific pathway is highly relevant and an important progress for malaria control programs.
2023-07-25 | GSE210626 | GEO
Project description:Differences between males and females are central to the biology of thousands of species across the tree of life. Sex chromosomes play a key role, but despite their their evolutionary diversity, the regulatory mechanisms have been mostly elucidated in the three model species Mammals, D. melanogaster and C. elegans. Here we present the characterization of the first X chromosome dosage compensation (DC) pathway in a non-model organism, the malaria mosquito Anopheles gambiae. In mosquitos, DC corrects the imbalance in gene expression between sexes by approximately two-fold upregulation of male X-linked genes. We have identified SOA, a previously uncharacterized gene, which is specific to Anophelinae and activated concomitantly with the onset of DC. SOA displays sex-specific alternative splicing, where only males express full-length protein. SOA is a DNA-binding protein, specifically localizes to an X chromosome territory and binds promoters of active X-linked genes. Expression of the male, but not female isoform, is sufficient to induce DC. SOA knock-out mosquitos display a male-specific developmental delay, which is associated with a global downregulation of the X chromosome. Thus, SOA is the first DC factor discovered in Anopheles and provides only the fourth DC pathway ever identified to date. Since only females are blood-feeding and able to transmit malaria, identification of this sex-specific pathway is highly relevant and an important progress for malaria control programs.
2023-07-25 | GSE210625 | GEO
Project description:In many species, males and females display differences in their physiology that are not limited to the gonads. Sex differences in adult insects can comprise body size and feeding behaviour, as only female, but not male mosquitoes are blood-feeding in order to produce eggs. This is relevant since the malaria-causing parasite Plasmodium is transmitted by a female mosquito through a previous blood meal from an infected individual. The initiation of sex-specific developmental programs can be often linked to heteromorphic sex chromosomes (XX/XY in Anopheles). In males, the X-linked genes are only present in a single copy. To counteract this hemizygosity, Anopheles, like other species, exhibits dosage compensation (DC). Anopheles DC manifests by upregulation of the single male X ensuring the equal expression of sex-chromosomal genes between males and females. To date, the sex-specific differences at the transcriptome level related to the X/Y chromosomes and DC have been characterized at post-embryonic stages. Their onset during embryogenesis, especially during the early stages where the embryo switches from the maternal to the zygotic transcriptome, is largely uncharacterized to date. Here, we generate a sex-specific transcriptome atlas across Anopheles embryogenesis ending at the first larval stage. Along with the transition from the maternal to the zygotic transcriptome, many transcripts switch isoform, where the 3’ untranslated regions (UTR) of zygotic transcripts are significantly extended compared to their maternal counterpart. We also identify stage- and sex-specific splicing events. Comparing male and female embryos, we identify 120 sexually dimorphic protein coding genes and non-coding RNAs, indicating that sexually dimorphic gene expression is not widespread during embryogenesis. Furthermore, the imbalance of X-linked genes between males and females after zygotic genome activation is corrected shortly after, where the majority of genes exhibit DC around 9 hours of embryogenesis with further fine-tuning later in development. Our atlas provides a framework to explore sex differences in development and evolution and thereby, enables future functional analyses of sex-specific expression patterns and isoform usage.
2023-07-25 | GSE210624 | GEO
Project description:Heteromorphic sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies and mammals. The reason for these mechanistic differences remain unclear: Are they a consequence of distinct genomes and gene content, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The X chromosomes of Anopheles and Drosophila evolved independently, yet from the same ancestral autosome and share a high degree of homology. We find that Anopheles achieves DC by an entirely different mechanism compared to the MSL complex - H4K16ac axis operating in Drosophila. CRISPR knock-out of msl-2 in Anopheles leads to early embryonic lethality and affects both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC, but instead relates to misregulation of developmental genes. Furthermore, Histone H4 Lysine 16 acetylation does not mark an X chromosome territory, neither does it display a sexually dimorphic genome-wide distribution by ChIP. We conclude that a novel pathway confers X chromosome upregulation in male Anopheles. Our findings highlight the pluralism of how organisms cope with gene-dosage alterations and show that different mechanisms can evolve even in scenarios of highly similar genomic and functional constraints.
2021-05-31 | GSE153778 | GEO