Identification of constrained sequence elements across 239 primate genomes

	Identification of constrained sequence elements across 239 primate genomes
	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, DD; Zhou, L; Shao, Y; Zhang, GJ; 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; Bonet, TM; Farh, KKH
	2024
发表期刊	NATURE
ISSN	0028-0836
卷号	625 期号:7996
摘要	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. Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14518
专题	科研部门_进化与发育转录组学（吴东东）
推荐引用方式 GB/T 7714	Kuderna, LFK,Ulirsch, JC,Rashid, S,et al. Identification of constrained sequence elements across 239 primate genomes[J]. NATURE,2024,625(7996).
APA	Kuderna, LFK.,Ulirsch, JC.,Rashid, S.,Ameen, M.,Sundaram, L.,...&Farh, KKH.(2024).Identification of constrained sequence elements across 239 primate genomes.NATURE,625(7996).
MLA	Kuderna, LFK,et al."Identification of constrained sequence elements across 239 primate genomes".NATURE 625.7996(2024).

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