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.
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.
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.
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.
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.