Three-dimensional genome rewiring in loci with human accelerated regions.
Kathleen C KeoughSean WhalenFumitaka InouePawel F PrzytyckiTyler FairChengyu DengMarilyn SteyertHane RyuKerstin Lindblad-TohElinor K Karlssonnull nullTomasz Jan NowakowskiNadav AhituvAlex Aaron PollenKatherine S PollardGregory AndrewsJoel C ArmstrongMatteo BianchiBruce W BirrenKevin R BredemeyerAna M BreitMatthew J ChristmasHiram ClawsonJoana DamasFederica Di PalmaMark DiekhansMichael X DongEduardo EizirikKaili FanCornelia FanterNicole M FoleyKarin Forsberg-NilssonCarlos J GarciaJohn GatesySteven GazalDiane P GenereuxLinda GoodmanJenna GrimshawMichaela K HalseyAndrew J HarrisGlenn HickeyMichael HillerAllyson G HindleRobert M HubleyGraham M HughesJeremy JohnsonDavid JuanIrene M KaplowElinor K KarlssonKathleen C KeoughBogdan KirilenkoKlaus-Peter KoepfliJennifer M KorstianAmanda KowalczykSergey V KozyrevAlyssa J LawlerColleen LawlessThomas LehmannDanielle L LevesqueHarris A LewinXue LiAbigail LindKerstin Lindblad-TohAva Mackay-SmithVoichita D MarinescuTomas Marques-BonetVictor C MasonJennifer R S MeadowsWynn K MeyerJill E MooreLucas R MoreiraDiana D Moreno-SantillanKathleen M MorrillGerard MuntanéWilliam J MurphyArcadi NavarroMartin NweeiaSylvia OrtmannAustin OsmanskiBenedict PatenNicole S PaulatAndreas R PfenningBaDoi N PhanKatherine S PollardHenry E PrattDavid A RaySteven K ReillyJeb R RosenIrina RufLouise RyanOliver A RyderPardis C SabetiDaniel E SchäfferAitor SerresBeth ShapiroArian F A SmitMark SpringerChaitanya SrinivasanCynthia SteinerJessica M StorerKevin A M SullivanPatrick F SullivanElisabeth SundströmMegan A SuppleRoss SwoffordJoy-El TalbotEmma TeelingJason Turner-MaierAlejandro ValenzuelaFranziska WagnerOla WallermanChao WangJuehan WangZhiping WengAryn P WilderMorgan E WirthlinJames R XueXiaomeng ZhangPublished in: Science (New York, N.Y.) (2023)
Human accelerated regions (HARs) are conserved genomic loci that evolved at an accelerated rate in the human lineage and may underlie human-specific traits. We generated HARs and chimpanzee accelerated regions with an automated pipeline and an alignment of 241 mammalian genomes. Combining deep learning with chromatin capture experiments in human and chimpanzee neural progenitor cells, we discovered a significant enrichment of HARs in topologically associating domains containing human-specific genomic variants that change three-dimensional (3D) genome organization. Differential gene expression between humans and chimpanzees at these loci suggests rewiring of regulatory interactions between HARs and neurodevelopmental genes. Thus, comparative genomics together with models of 3D genome folding revealed enhancer hijacking as an explanation for the rapid evolution of HARs.