Identification of constrained sequence elements across 239 primate genomes
Resource type
Journal article
Creator (person)
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, Fabràcio
Byrne, Hazel
Sampaio, Iracilda
Farias, Izeni
Valsecchi, Joà£o
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
Date published
January 25, 2024
Abstract
Noncoding DNA is central to our understanding of human gene regulation and complex diseases , and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome . 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 DNA , the relatively short timescales separating primate species , and the previously limited availability of whole-genome sequences . 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 -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.
Journal title
Nature
Volume
625
Publisher
Springer Science and Business Media LLC
ISSN
0028-0836
eISSN
1476-4687
Date accepted
October 30, 2023
Official URL
Rights statement
In Copyright
Additional information
Full text available via the official URL