ArticleMolecular biology and evolution2020
Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels.
Article in Molecular biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- NOTCH2NLA gene amplification is associated with poor prognosis in breast cancer.Discover oncology · 2026Article
- Comprehensive Exploration of NOTCH2NLA Across Cancers and Its Potential Roles in Prognosis and Immune System Interactions.Current medicinal chemistry · 2026Article
- Evolutionary implications ofBrain communications · 2026Article
- Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.Future oncology (London, England) · 2025Review
- The Notch pathway: A guardian of cell fate during neurogenesis.Current opinion in cell biology · 2025Review
- Functional Divergence ofInternational journal of molecular sciences · 2025Article
- The multifaceted roles and diagnostic-therapeutic potential of LINC01410 in malignant tumors and non-malignant disorders.Frontiers in immunology · 2025Review
- Proteomics Can Rise to the Challenge of Pseudogenes' Coding Nature.Journal of proteome research · 2024Review
- Neuroimaging genomics as a window into the evolution of human sulcal organization.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes.Physiological reviews · 2023Review
- Brain Organization and Human Diseases.Cells · 2022Review
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- The Phenotypes and Mechanisms of NOTCH2NLC-Related GGC Repeat Expansion Disorders: a Comprehensive Review.Molecular neurobiology · 2022Review
- Dissecting the impact of regional identity and the oncogenic role of human-specific NOTCH2NL in an hESC model of H3.3G34R-mutant glioma.Cell stem cell · 2021Article
- 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.Translational psychiatry · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.
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