ArticleCell2022
Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 116 citations in OpenAlex.
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- Regulatory Evolution and the Genetic Basis of Human Brain Expansion.Journal of molecular evolution · 2026Review
- Developmental signaling reveals functionally enriched human-specific gene regulation in telencephalic progenitors.bioRxiv : the preprint server for biology · 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
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Emergence and evolution of protein-coding de novo genes.Nature reviews. Genetics · 2026Review
- Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems.Biotechnology journal · 2026Review
- A LINE-1 insertion upstream of FOXP2 promotes neuronal differentiation during primate evolution.Genome biology · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- In Vitro Massively Parallel Screening of Human Regulatory Elements Involved in Postcranial Skeletal Development for Differential Activity Compared to Chimpanzee.Genome biology and evolution · 2026Article
- Adaptive loss of function accelerated the evolution of ancient and modern human cognition.bioRxiv : the preprint server for biology · 2026Article
- 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
- Cross-species prediction reveals chromatin regions with increased accessibility in humans.Science advances · 2026Article
- Human-specific lncRNAs contributed critically to human evolution by distinctly regulating gene expression.eLife · 2026Article
- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Ancient regulatory evolution shapes individual language abilities in present-day humans.bioRxiv : the preprint server for biology · 2026Article
- Article
- The evolution of gene regulation in mammalian cerebellum development.Science (New York, N.Y.) · 2026Article
- Comparative Study on the In Vitro Fermentation Characteristics of Three Plant-Derived Polysaccharides with Different Structural Compositions.Foods (Basel, Switzerland) · 2026Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins. HAQERs are enriched for bivalent chromatin states, particularly in gastrointestinal and neurodevelopmental tissues, and genetic variants linked to neurodevelopmental disease. We developed a multiplex, single-cell in vivo enhancer assay to discover that rapid sequence divergence in HAQERs generated hominin-unique enhancers in the developing cerebral cortex. We propose that a lack of pleiotropic constraints and elevated mutation rates poised HAQERs for rapid adaptation and subsequent susceptibility to disease.
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Registered trials
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.