The evolutionary history of complex traits: implications of archaic admixture
Kuupäev
2024-09-26
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Ajakirja pealkiri
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Abstrakt
Aafrikas arenenud anatoomiliselt kaasaegsed inimesed (AKI) eksisteerisid koos teiste arhailiste inimrühmadega, keda teatakse Neandertali ja Denissi inimestena. Erinevad elupaigad oma ainulaadsete keskkonnast tingitud väljakutsetega, millega need kolm inimrühma enam kui 200 000 aasta jooksul kokku puutusid, põhjustasid tõenäoliselt ainulaadsed kohastumusmustrid. Kui AKI-d umbes 60 000 aastat tagasi Aafrikast välja rändasid ja kogu kogu maailma asustasid, kohtusid nad Euraasia eri osades nii Neandertali kui ka Denissi inimestega ning segunesid nendega. Nende minevikus toimunud segunemiste tulemusena sisaldavad praeguste mitte-aafriklaste genoomid endiselt ~2% neandertallaste DNA-d ja okeaanlaste genoomid sisaldavad lisaks 2–5% denislaste DNA-d.
Arhaililiste inimeste geenivariantide uurimine on paljastanud olulisi seoseid erinevate tunnustega, mis on seotud immunoloogia, käitumise, naha ja juuste omadustega ning erinevate keskkonnast tulenevate kohastumistega Meie arusaam arhailiste geenivariantide funktsionaalsest rollist tänapäeva inimestes on siiski piiratud, peamiselt geneetiliselt mitmekesiste populatsioonide genoomsete ja fenotüüpsete andmekogumite kättesaadavuse tõttu. See lõputöö kasutab ära kasvavaid funktsionaalseid ja genoomseid andmekogusid, et täiendada meie teadmisi Neandertali ja Denissi inimeste introgresseerunud DNA fenotüüpse, regulatoorse ja evolutsioonilise mõju kohta tänapäeva inimestele.
Esimene uuring keskendus introgresseerunud neandertallaste DNA mõjule tänapäeva inimeste haigustele ja mitte-haiguslikelefenotüüpidele. Teises teadustöös uurisime neandertallaste DNA rolli kaugelt toimivas regulatsioonis tänapäeva inimestel. Kolmandas uuringus kirjeldasime arhailise introgresseerunud DNA võimalikku mõju kohastumisele kahes Paapua Uus-Guinea mägismaa ja madaliku populatsioonis. Kõik kolm uuringut täiendasid meie teadmisi neandertallaste ja denislaste DNA evolutsioonilistest ja funktsionaalsetest rollidest tänapäeva inimestes. Need leiud aitavad meil paremini mõista arhailiste geenivariantide panust, rikastades meie teadmisi kahe väljasurnud inimrühma kohta.
Anatomically modern humans (AMHs), who evolved in Africa, co-existed with other archaic human groups known as Neandertals and Denisovans who lived in different parts of Eurasia. The distinct habitats with their unique environmental challenges that these three human groups were exposed to for more than 200,000 years likely resulted in unique adaptation patterns. When AMHs moved out of Africa around 60,000 years ago to permanently colonize the whole world, they met and admixed with both Neandertal and Denisovans in different parts of Eurasia. As a result of these past admixture events, the genomes of present-day non-Africans are still composed of ∼2% of Neandertal DNA, and the genomes of Oceanians contain an additional 2–5% of Denisovan DNA. The analysis of this introgressed DNA in present-day humans has shown significant links to different traits related to immunology, behavior, skin and hair traits and high altitude adaptation. However, our understanding of the functional role of archaic DNA in people today remains incomplete, largely due to biases in the availability of genomic and phenotypic datasets from genetically diverse populations. This thesis takes advantage of the growing number of newly generated functional and genomic datasets, to expand our knowledge about the phenotypical, regulatory, and evolutionary impact of Neandertal and Denisovan introgressed DNA on present-day humans. The first study focused on the significant role of introgressed Neandertal DNA on disease and non-disease behavioral phenotypes in present-day humans. The second study explored the role of Neandertal DNA on long-range regulatory effects in people today. Finally, the third study described the potential impact of archaic introgressed DNA on processes of local adaptation in two populations from the highlands and lowlands of Papua New Guinea. All three studies further expanded our understanding of the evolutionary and functional roles of Neandertal and Denisovan DNA in people today. Additionally, they offer valuable new insights into the biology of these two extinct human groups.
Anatomically modern humans (AMHs), who evolved in Africa, co-existed with other archaic human groups known as Neandertals and Denisovans who lived in different parts of Eurasia. The distinct habitats with their unique environmental challenges that these three human groups were exposed to for more than 200,000 years likely resulted in unique adaptation patterns. When AMHs moved out of Africa around 60,000 years ago to permanently colonize the whole world, they met and admixed with both Neandertal and Denisovans in different parts of Eurasia. As a result of these past admixture events, the genomes of present-day non-Africans are still composed of ∼2% of Neandertal DNA, and the genomes of Oceanians contain an additional 2–5% of Denisovan DNA. The analysis of this introgressed DNA in present-day humans has shown significant links to different traits related to immunology, behavior, skin and hair traits and high altitude adaptation. However, our understanding of the functional role of archaic DNA in people today remains incomplete, largely due to biases in the availability of genomic and phenotypic datasets from genetically diverse populations. This thesis takes advantage of the growing number of newly generated functional and genomic datasets, to expand our knowledge about the phenotypical, regulatory, and evolutionary impact of Neandertal and Denisovan introgressed DNA on present-day humans. The first study focused on the significant role of introgressed Neandertal DNA on disease and non-disease behavioral phenotypes in present-day humans. The second study explored the role of Neandertal DNA on long-range regulatory effects in people today. Finally, the third study described the potential impact of archaic introgressed DNA on processes of local adaptation in two populations from the highlands and lowlands of Papua New Guinea. All three studies further expanded our understanding of the evolutionary and functional roles of Neandertal and Denisovan DNA in people today. Additionally, they offer valuable new insights into the biology of these two extinct human groups.
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