ArticleNature ecology & evolution2025
Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology.
Article in Nature ecology & evolution, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Chromosome X-wide association study in multiple system atrophy identifies sex-differential risk loci.Brain : a journal of neurology · 2026Article
- Y-Linked Expression Signatures Distinguish Dysfunctional Testicular States in Sheep.Animals : an open access journal from MDPI · 2026Article
- Escape from X inactivation varies across genes and tissues and shapes sex-biased sex chromosome gene expression.BMC genomics · 2026Article
- Gonadal and sex chromosomal contributions to sex differences in mammalian brain organization.bioRxiv : the preprint server for biology · 2026Article
- Reproducible autosomal gene expression changes with loss of typical X and Y complement across tumor types.bioRxiv : the preprint server for biology · 2025Article
- An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells.Genome research · 2025Article
- A cross-species analysis of neuroanatomical covariance sex differences in humans and mice.Biology of sex differences · 2025Article
- Heightened interest in the human X and Y chromosomes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks.Open biology · 2024Review
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Authors and funding
5 authors.
Funding
Abstract
Sex chromosomes are a fundamental aspect of sex-biased biology, but the extent to which homologous X-Y gene pairs ('the gametologs') contribute to sex-biased phenotypes remains hotly debated. Although these genes tend to exhibit large sex differences in expression throughout the body (XX females can express both X members, and XY males can express one X and one Y member), there is conflicting evidence regarding the degree of functional divergence between the X and Y members. Here we develop and apply co-expression fingerprint analysis to characterize functional divergence between the X and Y members of 17 gametolog gene pairs across >40 human tissues. Gametolog pairs exhibit functional divergence between the sexes that is driven by divergence between the X versus Y members (assayed in males), and this within-pair divergence is greatest among pairs with evolutionarily distant X and Y members. These patterns reflect that X versus Y gametologs show coordinated patterns of asymmetric coupling with large sets of autosomal genes, which are enriched for functional pathways and gene sets implicated in sex-biased biology and disease. Our findings suggest that the X versus Y gametologs have diverged in function and prioritize specific gametolog pairs for future targeted experimental studies.
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