2024
Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals
Uebbing S, Kocher A, Baumgartner M, Ji Y, Bai S, Xing X, Nottoli T, Noonan J. Evolutionary Innovations in Conserved Regulatory Elements Associate With Developmental Genes in Mammals. Molecular Biology And Evolution 2024, 41: msae199. PMID: 39302728, PMCID: PMC11465374, DOI: 10.1093/molbev/msae199.Peer-Reviewed Original ResearchSequence evolutionRegulatory evolutionDevelopmental signaling genesEnhanced evolutionEvolutionary innovationMammalian phylogenyTranscriptional enhancersGenetic variationPhenotypic variationPleiotropic genesDevelopmental genesEnhancer elementsHoofed mammalsEnhancer sequencesActivation domainSignaling genesEvolutionary adaptationDiverse organismsGenesHuman diseasesRegulatory functionsDevelopmental processesDeveloping limbCell typesMammalsMassively parallel disruption of enhancers active in human neural stem cells
Geller E, Noble M, Morales M, Gockley J, Emera D, Uebbing S, Cotney J, Noonan J. Massively parallel disruption of enhancers active in human neural stem cells. Cell Reports 2024, 43: 113693. PMID: 38271204, PMCID: PMC11078116, DOI: 10.1016/j.celrep.2024.113693.Peer-Reviewed Original ResearchHuman neural stem cellsNeural stem cellsStem cellsProliferation phenotypeAssociated with neurodevelopmental disordersNeurodevelopmental disordersEnhanced disruptionHuman Accelerated RegionsNeural progenitor proliferationEffects of genetic variationHuman cortical evolutionProgenitor proliferationSelf-renewalNeural progenitorsProgenitor populationsCerebral cortexChromatin interactionsHuman cerebral cortexNeural progenitor populationsGene regulationRegulatory elementsConserved regionGene disruptionGenetic variationRegulatory relationships
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolution