ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2013
Many human accelerated regions are developmental enhancers.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 3 of them syntheses that pooled it.
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Who cites it
145 citing papers in PubMed, 3 syntheses or guidelines pooled it, 261 citations in OpenAlex.
- A Systematic Review of the Human Accelerated Regions in Schizophrenia and Related Disorders: Where the Evolutionary and Neurodevelopmental Hypotheses Converge.International journal of molecular sciences · 2023Pooled it
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions.Molecular biology and evolution · 2015Pooled it
- A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development.bioRxiv : the preprint server for biology · 2026Article
- Differentially Methylated Regions in Human Rhombic Lip Compartments Are Enriched in Putative Active Enhancers, Human Accelerated Regions, and Medulloblastoma Copy Number Aberrations.Cerebellum (London, England) · 2026Article
- Positive selection on brain cis-regulatory elements in the human lineage drives changes in gene expression and susceptibility to neuropsychiatric disorders.HGG advances · 2026Article
- Article
- Ancient regulatory evolution shapes individual language abilities in present-day humans.Science advances · 2026Article
- Genomic-microbial coevolution in human development: chromosome 2 fusion, and human accelerated regions.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.Cell stem cell · 2026Article
- Inference of Autism Risk Genes Through Comparative Sociogenomics and Molecular Network Analysis.Genes · 2026Article
- So Fragile, So Human: Noncoding DNA Regions Orchestrating Gene Expression Involved in Neurodevelopmental Disorders and in Human Brain Evolution.International journal of molecular sciences · 2026Review
- Ancient regulatory evolution shapes individual language abilities in present-day humans.bioRxiv : the preprint server for biology · 2026Article
- Neurodevelopmentally rooted epicenters in schizophrenia: sensorimotor-association spatial axis of cortical thickness alterations.Molecular psychiatry · 2026Article
- A compendium of chromatin interaction maps in the Giant Panda genome.Communications biology · 2026Article
- Characterizing and decoding ultraconserved regions uncovers their regulatory significance in human brain development and disorders.Communications biology · 2025Article
- Motif-based models accurately predict cell type-specific distal regulatory elements.Nature communications · 2025Article
- Neocortical neurogenesis: a proneural gene perspective.The FEBS journal · 2025Review
- Epigenomic landscape of the developing human rhombic lip reveals gene regulatory network and non-coding loci of developmental, evolutionary, and disease relevance.bioRxiv : the preprint server for biology · 2025Article
- Comparative genomics sheds light on mammalian and avian gene regulation and phenotypic evolution.Nature communications · 2025Article
85 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
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Abstract
The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology.
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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.