ArticleMolecular biology and evolution2016
Strong Constraint on Human Genes Escaping X-Inactivation Is Modulated by their Expression Level and Breadth in Both Sexes.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- HJ Muller and the Relationship Between Sex Chromosome Degeneration and the Evolution of Dosage Compensation.Genome biology and evolution · 2025Review
- Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology.Nature ecology & evolution · 2025Article
- Sex Chromosome Evolution: Hallmarks and Question Marks.Molecular biology and evolution · 2024Review
- XIST dampens X chromosome activity in a SPEN-dependent manner during early human development.Nature structural & molecular biology · 2024Article
- Leveraging sex-genetic interactions to understand brain disorders: recent advances and current gaps.Brain communications · 2024Review
- Article
- Sex and gender in neurodevelopmental conditions.Nature reviews. Neurology · 2023Review
- Relating pathogenic loss-of-function mutations in humans to their evolutionary fitness costs.eLife · 2023Article
- Sex differences in normal and malignant hematopoiesis.Blood science (Baltimore, Md.) · 2022Review
- X chromosome inactivation in the human placenta is patchy and distinct from adult tissues.HGG advances · 2022Article
- Inferring genes that escape X-Chromosome inactivation reveals important contribution of variable escape genes to sex-biased diseases.Genome research · 2021Article
- Expression Evolution of Ancestral XY Gametologs across All Major Groups of Placental Mammals.Genome biology and evolution · 2020Article
- X chromosome genetic data in a Spanish children cohort, dataset description and analysis pipeline.Scientific data · 2019Article
- Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children's Cohort and Implications of the Gene in Adipocyte Metabolism.Scientific reports · 2019Article
- Sexual dimorphism in solid and hematological malignancies.Seminars in immunopathology · 2019Review
- New Advances in Human X chromosome status from a Developmental and Stem Cell Biology.Tissue engineering and regenerative medicine · 2017Article
- When the Lyon(ized chromosome) roars: ongoing expression from an inactive X chromosome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Dosage compensation of the sex chromosomes and autosomes.Seminars in cell & developmental biology · 2016Review
Corrections and comments
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4 authors.
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Abstract
In eutherian mammals, X-linked gene expression is normalized between XX females and XY males through the process of X chromosome inactivation (XCI). XCI results in silencing of transcription from one ChrX homolog per female cell. However, approximately 25% of human ChrX genes escape XCI to some extent and exhibit biallelic expression in females. The evolutionary basis of this phenomenon is not entirely clear, but high sequence conservation of XCI escapers suggests that purifying selection may directly or indirectly drive XCI escape at these loci. One hypothesis is that this signal results from contributions to developmental and physiological sex differences, but presently there is limited evidence supporting this model in humans. Another potential driver of this signal is selection for high and/or broad gene expression in both sexes, which are strong predictors of reduced nucleotide substitution rates in mammalian genes. Here, we compared purifying selection and gene expression patterns of human XCI escapers with those of X-inactivated genes in both sexes. When we accounted for the functional status of each ChrX gene's Y-linked homolog (or "gametolog"), we observed that XCI escapers exhibit greater degrees of purifying selection in the human lineage than X-inactivated genes, as well as higher and broader gene expression than X-inactivated genes across tissues in both sexes. These results highlight a significant role for gene expression in both sexes in driving purifying selection on XCI escapers, and emphasize these genes' potential importance in human disease.
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