ArticleCell systems2018
Fast-Evolving Human-Specific Neural Enhancers Are Associated with Aging-Related Diseases.
Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target.Nature reviews. Molecular cell biology · 2026Review
- Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.Cell stem cell · 2026Article
- Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis.Nature communications · 2025Article
- An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes.Genome research · 2024Article
- Encoding signal propagation on topology-programmed DNA origami.Nature chemistry · 2024Article
- Comparative three-dimensional genome architectures of adipose tissues provide insight into human-specific regulation of metabolic homeostasis.The Journal of biological chemistry · 2023Article
- Novel enhancer mediates theFrontiers in genetics · 2023Article
- Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum.Genome biology · 2022Article
- The developmental impacts of natural selection on human pelvic morphology.Science advances · 2022Article
- Epigenetics of neural differentiation: Spotlight on enhancers.Frontiers in cell and developmental biology · 2022Review
- Human brain evolution: Emerging roles for regulatory DNA and RNA.Current opinion in neurobiology · 2021Review
- Comparable Number of Genes Having Experienced Positive Selection among Great Ape Species.Animals : an open access journal from MDPI · 2021Article
- Origin of Sex-Biased Mental Disorders: An Evolutionary Perspective.Journal of molecular evolution · 2021Review
- A High-Resolution Map of Human Enhancer RNA Loci Characterizes Super-enhancer Activities in Cancer.Cancer cell · 2020Article
- Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species.BMC genomics · 2020Review
- Ageing Throughout History: The Evolution of Human Lifespan.Journal of molecular evolution · 2020Review
- Gene regulation and the architecture of complex human traits in the genomics era.Current opinion in psychology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging-related diseases and enhancers acquired after the human-chimpanzee divergence. We report a 5-fold increased evolutionary rate of enhancers that are activated in neural tissues, leading to fixation of ∼100 human-specific enhancers potentially under adaptation. These enhancers show prognostic expression levels and correlations with driver genes in cancer, and their nearby genes are enriched in known loci associated with aging-related diseases. Using CRISPR/Cas9, we further functionally validated an enhancer on chr8p23.1 as activator counteracting REST, a master regulator known to be a transcriptional suppressor of Alzheimer disease. Our results suggest an evolutionary origin of aging-related diseases: the side effects of human-specific, neural-tissue expressed enhancers. Thus, adaptive molecular changes in human macroevolution may introduce vulnerabilities to disease development in modern populations.
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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.