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

Harvard

Kuderna, LFK, Ulirsch, JC, Rashid, S, Ameen, M, Sundaram, L, Hickey, G, Cox, AJ, Gao, H, Kumar, A, Aguet, F, Christmas, MJ, Clawson, H, Haeussler, M, Janiak, MC, Kuhlwilm, M, Orkin, JD, Bataillon, T, Manu, S, Valenzuela, A, Bergman, J, Rouselle, M, Silva, FE, Agueda, L, Blanc, J, Gut, M, de Vries, D, Goodhead, I, Harris, RA, Raveendran, M, Jensen, A, Chuma, IS, Horvath, JE, Hvilsom, C, Juan, D, Frandsen, P, Schraiber, JG, de Melo, FR, Bertuol, F, Byrne, H, Sampaio, I, Farias, I, Valsecchi, J, Messias, M, da Silva, MNF, Trivedi, M, Rossi, R, Hrbek, T, Andriaholinirina, N, Rabarivola, CJ, Zaramody, A, Jolly, CJ, Phillips-Conroy, J, Wilkerson, G, Abee, C, Simmons, JH, Fernandez-Duque, E, Kanthaswamy, S, Shiferaw, F, Wu, D, Zhou, L, Shao, Y, Zhang, G, Keyyu, JD, Knauf, S, Le, MD, Lizano, E, Merker, S, Navarro, A, Nadler, T, Khor, CC, Lee, J, Tan, P, Lim, WK, Kitchener, AC, Zinner, D, Gut, I, Melin, AD, Guschanski, K, Schierup, MH, Beck, RMD, Karakikes, I, Wang, KC, Umapathy, G, Roos, C, Boubli, JP, Siepel, A, Kundaje, A, Paten, B, Lindblad-Toh, K, Rogers, J, Marques Bonet, T & Farh, KKH 2024, 'Identification of constrained sequence elements across 239 primate genomes', Nature, bind 625, s. 735–742. https://doi.org/10.1038/s41586-023-06798-8

APA

Kuderna, L. F. K., Ulirsch, J. C., Rashid, S., Ameen, M., Sundaram, L., Hickey, G., Cox, A. J., Gao, H., Kumar, A., Aguet, F., Christmas, M. J., Clawson, H., Haeussler, M., Janiak, M. C., Kuhlwilm, M., Orkin, J. D., Bataillon, T., Manu, S., Valenzuela, A., ... Farh, K. K. H. (2024). Identification of constrained sequence elements across 239 primate genomes. Nature, 625, 735–742. https://doi.org/10.1038/s41586-023-06798-8

Vancouver

Kuderna LFK, Ulirsch JC, Rashid S, Ameen M, Sundaram L, Hickey G o.a. Identification of constrained sequence elements across 239 primate genomes. Nature. 2024;625:735–742. https://doi.org/10.1038/s41586-023-06798-8

Author

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. / Identification of constrained sequence elements across 239 primate genomes. I: Nature. 2024 ; Bind 625. s. 735–742.

Bibtex

@article{421360a699b1437da3f8b972840461f9,

title = "Identification of constrained sequence elements across 239 primate genomes",

abstract = "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.",

author = "Kuderna, {Lukas F.K.} and Ulirsch, {Jacob C.} and Sabrina Rashid and Mohamed Ameen and Laksshman Sundaram and Glenn Hickey and Cox, {Anthony J.} and Hong Gao and Arvind Kumar and Francois Aguet and Christmas, {Matthew J.} and Hiram Clawson and Maximilian Haeussler and Janiak, {Mareike C.} and Martin Kuhlwilm and Orkin, {Joseph D.} and Thomas Bataillon and Shivakumara Manu and Alejandro Valenzuela and Juraj Bergman and Marjolaine Rouselle and Silva, {Felipe Ennes} and Lidia Agueda and Julie Blanc and Marta Gut and {de Vries}, Dorien and Ian Goodhead and Harris, {R. Alan} and Muthuswamy Raveendran and Axel Jensen and Chuma, {Idriss S.} and Horvath, {Julie E.} and Christina Hvilsom and David Juan and Peter Frandsen and Schraiber, {Joshua G.} and {de Melo}, {Fabiano R.} and Fabr{\'i}cio Bertuol and Hazel Byrne and Iracilda Sampaio and Izeni Farias and Jo{\~a}o Valsecchi and Malu Messias and {da Silva}, {Maria N.F.} and Mihir Trivedi and Rogerio Rossi and Tomas Hrbek and Nicole Andriaholinirina and Rabarivola, {Cl{\'e}ment J.} and Alphonse Zaramody and Jolly, {Clifford J.} and Jane Phillips-Conroy and Gregory Wilkerson and Christian Abee and Simmons, {Joe H.} and Eduardo Fernandez-Duque and Sree Kanthaswamy and Fekadu Shiferaw and Dongdong Wu and Long Zhou and Yong Shao and Guojie Zhang and Keyyu, {Julius D.} and Sascha Knauf and Le, {Minh D.} and Esther Lizano and Stefan Merker and Arcadi Navarro and Tilo Nadler and Khor, {Chiea Chuen} and Jessica Lee and Patrick Tan and Lim, {Weng Khong} and Kitchener, {Andrew C.} and Dietmar Zinner and Ivo Gut and Melin, {Amanda D.} and Katerina Guschanski and Schierup, {Mikkel Heide} and Beck, {Robin M.D.} and Ioannis Karakikes and Wang, {Kevin C.} and Govindhaswamy Umapathy and Christian Roos and Boubli, {Jean P.} and Adam Siepel and Anshul Kundaje and Benedict Paten and Kerstin Lindblad-Toh and Jeffrey Rogers and {Marques Bonet}, Tomas and Farh, {Kyle Kai How}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2024",

doi = "10.1038/s41586-023-06798-8",

language = "English",

volume = "625",

pages = "735–742",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

}

RIS

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

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

Biologisk Institut