Denisovan introgression has shaped the immune system of present-day Papuans
| العنوان: | Denisovan introgression has shaped the immune system of present-day Papuans |
|---|---|
| المؤلفون: | Davide M. Vespasiani, Guy S. Jacobs, Laura E. Cook, Nicolas Brucato, Matthew Leavesley, Christopher Kinipi, François-Xavier Ricaut, Murray P. Cox, Irene Gallego Romero |
| المساهمون: | Vespasiani, Davide M [0000-0002-0977-8076], Cook, Laura E [0000-0002-4459-2592], Leavesley, Matthew [0000-0002-4612-8304], Cox, Murray P [0000-0003-1936-0236], Gallego Romero, Irene [0000-0003-1613-8998], Apollo - University of Cambridge Repository |
| بيانات النشر: | Public Library of Science (PLoS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Biology and life sciences, FOS: Social sciences, Hominidae, Social sciences, Evolution, Molecular, Papua New Guinea, Earth sciences, Immune System, Genetics, Humans, Molecular Biology, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Neanderthals, Research Article |
| الوصف: | Acknowledgements: We would like to thank all members of the Gallego Romero and McCarthy groups for their helpful discussions and comments on the manuscript. We also wish to acknowledge all of the study participants who generously consented to genome sequencing in the original study, and the leadership of Herawati Sudoyo and Chelzie Crenna Darusalam (Eijkman Institute for Molecular Biology) in generating these datasets. Funder: Leakey Foundation; funder-id: http://dx.doi.org/10.13039/100005966Test Funder: University of Melbourne; funder-id: http://dx.doi.org/10.13039/501100001782Test Modern humans have admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of both Denisovan and Neanderthal alleles characterised within a set of 56 genomes from Papuan individuals. By comparing the distribution of archaic and non-archaic variants we assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We observe an enrichment of archaic alleles within cis-regulatory elements and transcribed regions of the genome, with Denisovan variants strongly affecting elements active within immune-related cells. We identify 16,048 and 10,032 high-confidence Denisovan and Neanderthal variants that fall within annotated cis-regulatory elements and with the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activity in plasmid reporter assays. Together, these data provide support for a widespread contribution of archaic DNA in shaping the present levels of modern human genetic diversity, with different archaic ancestries potentially affecting multiple phenotypic traits within non-Africans. |
| وصف الملف: | application/pdf; application/zip; text/xml |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ac0eba8e7af4c8a59807c6a41f9fbd0Test https://www.repository.cam.ac.uk/handle/1810/344141Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4ac0eba8e7af4c8a59807c6a41f9fbd0 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |