ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 194 citations in OpenAlex.
- Sex Differences and Oxidative Stress in Cardiovascular Disease.Physiology (Bethesda, Md.) · 2026Review
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Review
- Sex as a biological variable in human dental pulp stem cells: An exploratory epigenomic and transcriptomic comparison.Regenerative therapy · 2026Article
- HJ Muller and the Relationship Between Sex Chromosome Degeneration and the Evolution of Dosage Compensation.Genome biology and evolution · 2025Review
- X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels.Nature communications · 2025Article
- Gene Dosage Sensitivity and Human Genetic Diseases.Journal of inherited metabolic disease · 2025Review
- Role of X chromosome and dosage-compensation mechanisms in complex trait genetics.American journal of human genetics · 2025Article
- Repeated Evolution of Transcript Dosage Compensation of Independently Formed Nematode Neo-X Chromosomes.Genome biology and evolution · 2025Article
- Sex-Specific Effects of Environmental Pollutants on Pulmonary Immune Responses.Current opinion in physiology · 2025Article
- Human Single-Cell RNA-Sequencing Data Supports the Hypothesis of X Chromosome Insensitivity but Is Ineffective in Testing the Dosage Compensation Model.Molecular biology and evolution · 2025Article
- Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.Stem cell reports · 2024Article
- Sex Chromosome Evolution: Hallmarks and Question Marks.Molecular biology and evolution · 2024Review
- Compensation of gene dosage on the mammalian X.Development (Cambridge, England) · 2024Review
- Inverse and ProportionalGenes · 2024Article
- Gene dosage compensation: Origins, criteria to identify compensated genes, and mechanisms including sensor loops as an emerging systems-level property in cancer.Cancer medicine · 2023Review
- A fine balancing act: how epitranscriptome regulates dosage compensation in mammals.Nature structural & molecular biology · 2023Article
- RNA stability controlled by mNature structural & molecular biology · 2023Article
- Article
- The compleX balancing act of controlling X-chromosome dosage and how it impacts mammalian germline development.The Biochemical journal · 2023Article
63 more citing papers are in PubMed but not listed here.
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5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How and why female somatic X-chromosome inactivation (XCI) evolved in mammals remains poorly understood. It has been proposed that XCI is a dosage-compensation mechanism that evolved to equalize expression levels of X-linked genes in females (2X) and males (1X), with a prior twofold increase in expression of X-linked genes in both sexes ("Ohno's hypothesis"). Whereas the parity of X chromosome expression between the sexes has been clearly demonstrated, tests for the doubling of expression levels globally along the X chromosome have returned contradictory results. However, changes in gene dosage during sex-chromosome evolution are not expected to impact on all genes equally, and should have greater consequences for dosage-sensitive genes. We show that, for genes encoding components of large protein complexes (≥ 7 members)--a class of genes that is expected to be dosage-sensitive--expression of X-linked genes is similar to that of autosomal genes within the complex. These data support Ohno's hypothesis that XCI acts as a dosage-compensation mechanism, and allow us to refine Ohno's model of XCI evolution. We also explore the contribution of dosage-sensitive genes to X aneuploidy phenotypes in humans, such as Turner (X0) and Klinefelter (XXY) syndromes. X aneuploidy in humans is common and is known to have mild effects because most of the supernumerary X genes are inactivated and not affected by aneuploidy. Only genes escaping XCI experience dosage changes in X-aneuploidy patients. We combined data on dosage sensitivity and XCI to compute a list of candidate genes for X-aneuploidy syndromes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.