Identification of constrained sequence elements across 239 primate genomes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Identification of constrained sequence elements across 239 primate genomes. / Kuderna, Lukas F.K.; Ulirsch, Jacob C.; Rashid, Sabrina; Ameen, Mohamed; Sundaram, Laksshman; Hickey, Glenn; Cox, Anthony J.; Gao, Hong; Kumar, Arvind; Aguet, Francois; Christmas, Matthew J.; Clawson, Hiram; Haeussler, Maximilian; Janiak, Mareike C.; Kuhlwilm, Martin; Orkin, Joseph D.; Bataillon, Thomas; Manu, Shivakumara; Valenzuela, Alejandro; Bergman, Juraj; Rouselle, Marjolaine; Silva, Felipe Ennes; Agueda, Lidia; Blanc, Julie; Gut, Marta; de Vries, Dorien; Goodhead, Ian; Harris, R. Alan; Raveendran, Muthuswamy; Jensen, Axel; Chuma, Idriss S.; Horvath, Julie E.; Hvilsom, Christina; Juan, David; Frandsen, Peter; Schraiber, Joshua G.; de Melo, Fabiano R.; Bertuol, Fabrício; Byrne, Hazel; Sampaio, Iracilda; Farias, Izeni; Valsecchi, João; Messias, Malu; da Silva, Maria N.F.; Trivedi, Mihir; Rossi, Rogerio; Hrbek, Tomas; Andriaholinirina, Nicole; Rabarivola, Clément J.; Zaramody, Alphonse; Jolly, Clifford J.; Phillips-Conroy, Jane; Wilkerson, Gregory; Abee, Christian; Simmons, Joe H.; Fernandez-Duque, Eduardo; Kanthaswamy, Sree; Shiferaw, Fekadu; Wu, Dongdong; Zhou, Long; Shao, Yong; Zhang, Guojie; Keyyu, Julius D.; Knauf, Sascha; Le, Minh D.; Lizano, Esther; Merker, Stefan; Navarro, Arcadi; Nadler, Tilo; Khor, Chiea Chuen; Lee, Jessica; Tan, Patrick; Lim, Weng Khong; Kitchener, Andrew C.; Zinner, Dietmar; Gut, Ivo; Melin, Amanda D.; Guschanski, Katerina; Schierup, Mikkel Heide; Beck, Robin M.D.; Karakikes, Ioannis; Wang, Kevin C.; Umapathy, Govindhaswamy; Roos, Christian; Boubli, Jean P.; Siepel, Adam; Kundaje, Anshul; Paten, Benedict; Lindblad-Toh, Kerstin; Rogers, Jeffrey; Marques Bonet, Tomas; Farh, Kyle Kai How.
I: Nature, Bind 625, 2024, s. 735–742.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of constrained sequence elements across 239 primate genomes
AU - Kuderna, Lukas F.K.
AU - Ulirsch, Jacob C.
AU - Rashid, Sabrina
AU - Ameen, Mohamed
AU - Sundaram, Laksshman
AU - Hickey, Glenn
AU - Cox, Anthony J.
AU - Gao, Hong
AU - Kumar, Arvind
AU - Aguet, Francois
AU - Christmas, Matthew J.
AU - Clawson, Hiram
AU - Haeussler, Maximilian
AU - Janiak, Mareike C.
AU - Kuhlwilm, Martin
AU - Orkin, Joseph D.
AU - Bataillon, Thomas
AU - Manu, Shivakumara
AU - Valenzuela, Alejandro
AU - Bergman, Juraj
AU - Rouselle, Marjolaine
AU - Silva, Felipe Ennes
AU - Agueda, Lidia
AU - Blanc, Julie
AU - Gut, Marta
AU - de Vries, Dorien
AU - Goodhead, Ian
AU - Harris, R. Alan
AU - Raveendran, Muthuswamy
AU - Jensen, Axel
AU - Chuma, Idriss S.
AU - Horvath, Julie E.
AU - Hvilsom, Christina
AU - Juan, David
AU - Frandsen, Peter
AU - Schraiber, Joshua G.
AU - de Melo, Fabiano R.
AU - Bertuol, Fabrício
AU - Byrne, Hazel
AU - Sampaio, Iracilda
AU - Farias, Izeni
AU - Valsecchi, João
AU - Messias, Malu
AU - da Silva, Maria N.F.
AU - Trivedi, Mihir
AU - Rossi, Rogerio
AU - Hrbek, Tomas
AU - Andriaholinirina, Nicole
AU - Rabarivola, Clément J.
AU - Zaramody, Alphonse
AU - Jolly, Clifford J.
AU - Phillips-Conroy, Jane
AU - Wilkerson, Gregory
AU - Abee, Christian
AU - Simmons, Joe H.
AU - Fernandez-Duque, Eduardo
AU - Kanthaswamy, Sree
AU - Shiferaw, Fekadu
AU - Wu, Dongdong
AU - Zhou, Long
AU - Shao, Yong
AU - Zhang, Guojie
AU - Keyyu, Julius D.
AU - Knauf, Sascha
AU - Le, Minh D.
AU - Lizano, Esther
AU - Merker, Stefan
AU - Navarro, Arcadi
AU - Nadler, Tilo
AU - Khor, Chiea Chuen
AU - Lee, Jessica
AU - Tan, Patrick
AU - Lim, Weng Khong
AU - Kitchener, Andrew C.
AU - Zinner, Dietmar
AU - Gut, Ivo
AU - Melin, Amanda D.
AU - Guschanski, Katerina
AU - Schierup, Mikkel Heide
AU - Beck, Robin M.D.
AU - Karakikes, Ioannis
AU - Wang, Kevin C.
AU - Umapathy, Govindhaswamy
AU - Roos, Christian
AU - Boubli, Jean P.
AU - Siepel, Adam
AU - Kundaje, Anshul
AU - Paten, Benedict
AU - Lindblad-Toh, Kerstin
AU - Rogers, Jeffrey
AU - Marques Bonet, Tomas
AU - Farh, Kyle Kai How
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2024
Y1 - 2024
N2 - Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
AB - Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
U2 - 10.1038/s41586-023-06798-8
DO - 10.1038/s41586-023-06798-8
M3 - Journal article
C2 - 38030727
AN - SCOPUS:85177798736
VL - 625
SP - 735
EP - 742
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 375205301