A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome

doi:10.1186/s13059-025-03502-z

IVPP-IR

	A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome
	Liang, Shen-Ao 1; Ren, Tianxin 2; Zhang, Jiayu 1; He, Jiahui 3; Wang, Xuankai 2; Jiang, Xinrui 2; He, Yuan 3; Mccoy, Rajiv C.4; Fu, Qiaomei5,6 ; Akey, Joshua M.7; Mao, Yafei 2,8; Chen, Lu 1
	2025-02-17
发表期刊	GENOME BIOLOGY
ISSN	1474-760X
卷号	26 期号:1 页码:20
通讯作者	Mao, Yafei(yafmao@sjtu.edu.cn) ; Chen, Lu(lu_chen@fudan.edu.cn)
摘要	BackgroundLeveraging long-read sequencing technologies, the first complete human reference genome, T2T-CHM13, corrects assembly errors in previous references and resolves the remaining 8% of the genome. While studies on archaic admixture in modern humans have so far relied on the GRCh37 reference due to the availability of archaic genome data, the impact of T2T-CHM13 in this field remains unexplored.ResultsWe remap the sequencing reads of the high-quality Altai Neanderthal and Denisovan genomes onto GRCh38 and T2T-CHM13. Compared to GRCh37, we find that T2T-CHM13 significantly improves read mapping quality in archaic samples. We then apply IBDmix to identify Neanderthal-introgressed sequences in 2504 individuals from 26 geographically diverse populations using different reference genomes. We observe that commonly used pre-phasing filtering strategies in public datasets substantially influence archaic ancestry determination, underscoring the need for careful filter selection. Our analysis identifies approximately 51 Mb of Neanderthal sequences unique to T2T-CHM13, predominantly in genomic regions where GRCh38 and T2T-CHM13 assemblies diverge. Additionally, we uncover novel instances of population-specific archaic introgression in diverse populations, spanning genes involved in metabolism, olfaction, and ion-channel function. Finally, to facilitate the exploration of archaic alleles and adaptive signals in human genomics and evolutionary research, we integrate these introgressed sequences and adaptive signals across all reference genomes into a visualization database, ASH (www.arcseqhub.com).ConclusionsOur study enhances the detection of archaic variations in modern humans, highlights the importance of utilizing the T2T-CHM13 reference, and provides novel insights into the functional consequences of archaic hominin admixture.
关键词	T2T-CHM13 Archaic admixture Adaptive introgression Database Complete human genome sequence
DOI	10.1186/s13059-025-03502-z
关键词[WOS]	ANCESTRY ; ADAPTATION ; DISCOVERY ; FRAMEWORK ; ADMIXTURE ; CAVE ; DNA
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[32270668] ; The 111 project[B25056] ; Natural Science Foundation of Chongqing, China[CSTB2024NSCQ- JQX0004] ; Shanghai Jiao Tong University 2030 Initiative[WH510363003/016]
项目资助者	National Natural Science Foundation of China ; The 111 project ; Natural Science Foundation of Chongqing, China ; Shanghai Jiao Tong University 2030 Initiative
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity
WOS记录号	WOS:001423539300001
出版者	BMC
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.205/handle/311034/24369
专题	中国科学院古脊椎动物与古人类研究所
通讯作者	Mao, Yafei; Chen, Lu
作者单位	1.Fudan Univ, Ctr Evolutionary Biol, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200438, Peoples R China 2.Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China 3.Fudan Univ, Ctr Evolutionary Biol, Sch Life Sci, Minist Educ,Key Lab Contemporary Anthropol, Shanghai 200438, Peoples R China 4.Johns Hopkins Univ, Dept Biol, Baltimore, MD 21212 USA 5.Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA 8.Zhejiang Univ, Affiliated Hosp 4, Int Inst Med, Ctr Genom Res, Yiwu 322000, Peoples R China
推荐引用方式 GB/T 7714	Liang, Shen-Ao,Ren, Tianxin,Zhang, Jiayu,et al. A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome[J]. GENOME BIOLOGY,2025,26(1):20.
APA	Liang, Shen-Ao.,Ren, Tianxin.,Zhang, Jiayu.,He, Jiahui.,Wang, Xuankai.,...&Chen, Lu.(2025).A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome.GENOME BIOLOGY,26(1),20.
MLA	Liang, Shen-Ao,et al."A refined analysis of Neanderthal-introgressed sequences in modern humans with a complete reference genome".GENOME BIOLOGY 26.1(2025):20.