Genome diversity and signatures of natural selection in mainland Southeast Asia

Yaoxi He^#^{1

2}, Xiaoming Zhang^#^{1

2}, Min-Sheng Peng^#^{1

3

4}, Yu-Chun Li^#^{1

3

5}, Kai Liu^#^{1

4}, Yu Zhang^{1

4}, Leyan Mao^{1

4}, Yongbo Guo¹, Yujie Ma^{1

4}, Bin Zhou^{1

4}, Wangshan Zheng^{1

4}, Tian Yue^{1

4}, Yuwen Liao^{1

4}, Shen-Ao Liang⁶, Lu Chen⁶, Weijie Zhang^{1

4}, Xiaoning Chen⁷, Bixia Tang⁷, Xiaofei Yang^{8

9

10}, Kai Ye^{9

10

11

12

13

14}, Shenghan Gao^{8

9

11}, Yurun Lu¹⁵, Yong Wang¹⁵, Shijie Wan⁸, Rushan Hao¹⁶, Xuankai Wang¹⁷, Yafei Mao^{17

18}, Shanshan Dai¹, Zongliang Gao^{1

3

4

5}, Li-Qin Yang^{1

2

5}, Jianxin Guo¹, Jiangguo Li^{1

4}, Chao Liu^{19

20}, Jianhua Wang²¹, Tuot Sovannary²², Long Bunnath²², Jatupol Kampuansai²³, Angkhana Inta²³, Metawee Srikummool²⁴, Wibhu Kutanan²⁵, Huy Quang Ho²⁶, Khoa Dang Pham²⁶, Sommay Singthong²⁷, Somphad Sochampa²⁸, U Win Kyaing²⁹, Wittaya Pongamornkul³⁰, Chutima Morlaeku³¹, Kittisak Rattanakrajangsri³²; Consortium of Anthropological Research in Southeast Asia and Southwest China (CASEAC); Qing-Peng Kong^{33

34

35

36}, Ya-Ping Zhang^{37

38

39

40}, Bing Su^{41

42

43}

Affiliations

¹ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
² Yunnan Key Laboratory of Integrative Anthropology, Kunming, China.
³ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ Kunming Key Laboratory of Healthy Aging Study, Kunming, China.
⁶ State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Science, Fudan University, Shanghai, China.
⁷ National Genomics Data Center, China National Center for Bioinformation, Beijing, China.
⁸ School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
⁹ MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
¹⁰ Center for Mathematical Medical, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
¹¹ School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
¹² Genome Institute, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
¹³ School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
¹⁴ Faculty of Science, Leiden University, Leiden, The Netherlands.
¹⁵ CEMS, NCMIS, HCMS, MADIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
¹⁶ School of Medicine, Yunnan University, Kunming, China.
¹⁷ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
¹⁸ Center for Genomic Research, International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University, Yiwu, China.
¹⁹ Laboratory Animal Center, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, China.
²⁰ National Resource Center for Non-Human Primates, Kunming, China.
²¹ Department of Anthropology, School of Sociology, Yunnan Minzu University, Kunming, China.
²² Department of Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Cambodia.
²³ Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
²⁴ Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
²⁵ Department of Biology, Faculty of Science, Naresuan University, Phitsanulok, Thailand.
²⁶ Department of Immunology, Ha Noi Medical University, Ha Noi, Vietnam.
²⁷ National University of Laos (NUOL), Vientiane, Laos.
²⁸ Muang Sing District Hospital, Luang Namtha, Laos.
²⁹ Field School of Archaeology, Paukkhaung, Myanmar.
³⁰ Queen Sirikit Botanic Garden (QSBG), The Botanical Garden Organization, Chiang Mai, Thailand.
³¹ Inter Mountain Peoples Education and Culture in Thailand Association (IMPECT), Sansai, Thailand.
³² Asia Indigenous Peoples Pact (AIPP), Chiang Mai, Thailand.
³³ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁴ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁵ Kunming Key Laboratory of Healthy Aging Study, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁶ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁷ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. zhangyp@mail.kiz.ac.cn.
³⁸ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China. zhangyp@mail.kiz.ac.cn.
³⁹ University of Chinese Academy of Sciences, Beijing, China. zhangyp@mail.kiz.ac.cn.
⁴⁰ State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China. zhangyp@mail.kiz.ac.cn.
⁴¹ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. sub@mail.kiz.ac.cn.
⁴² Yunnan Key Laboratory of Integrative Anthropology, Kunming, China. sub@mail.kiz.ac.cn.
⁴³ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. sub@mail.kiz.ac.cn.

^# Contributed equally.

PMID: 40369069
DOI: 10.1038/s41586-025-08998-w

Genome diversity and signatures of natural selection in mainland Southeast Asia

Yaoxi He et al. Nature. 2025 Jul.

. 2025 Jul;643(8071):417-426.

doi: 10.1038/s41586-025-08998-w. Epub 2025 May 14.

Authors

Affiliations

¹ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
² Yunnan Key Laboratory of Integrative Anthropology, Kunming, China.
³ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China.
⁴ University of Chinese Academy of Sciences, Beijing, China.
⁵ Kunming Key Laboratory of Healthy Aging Study, Kunming, China.
⁶ State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Science, Fudan University, Shanghai, China.
⁷ National Genomics Data Center, China National Center for Bioinformation, Beijing, China.
⁸ School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
⁹ MOE Key Lab for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
¹⁰ Center for Mathematical Medical, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
¹¹ School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi'an Jiaotong University, Xi'an, China.
¹² Genome Institute, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
¹³ School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
¹⁴ Faculty of Science, Leiden University, Leiden, The Netherlands.
¹⁵ CEMS, NCMIS, HCMS, MADIS, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing, China.
¹⁶ School of Medicine, Yunnan University, Kunming, China.
¹⁷ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
¹⁸ Center for Genomic Research, International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University, Yiwu, China.
¹⁹ Laboratory Animal Center, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, China.
²⁰ National Resource Center for Non-Human Primates, Kunming, China.
²¹ Department of Anthropology, School of Sociology, Yunnan Minzu University, Kunming, China.
²² Department of Geography and Land Management, Royal University of Phnom Penh, Phnom Penh, Cambodia.
²³ Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
²⁴ Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand.
²⁵ Department of Biology, Faculty of Science, Naresuan University, Phitsanulok, Thailand.
²⁶ Department of Immunology, Ha Noi Medical University, Ha Noi, Vietnam.
²⁷ National University of Laos (NUOL), Vientiane, Laos.
²⁸ Muang Sing District Hospital, Luang Namtha, Laos.
²⁹ Field School of Archaeology, Paukkhaung, Myanmar.
³⁰ Queen Sirikit Botanic Garden (QSBG), The Botanical Garden Organization, Chiang Mai, Thailand.
³¹ Inter Mountain Peoples Education and Culture in Thailand Association (IMPECT), Sansai, Thailand.
³² Asia Indigenous Peoples Pact (AIPP), Chiang Mai, Thailand.
³³ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁴ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁵ Kunming Key Laboratory of Healthy Aging Study, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁶ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. kongqp@mail.kiz.ac.cn.
³⁷ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. zhangyp@mail.kiz.ac.cn.
³⁸ KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China. zhangyp@mail.kiz.ac.cn.
³⁹ University of Chinese Academy of Sciences, Beijing, China. zhangyp@mail.kiz.ac.cn.
⁴⁰ State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, China. zhangyp@mail.kiz.ac.cn.
⁴¹ State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. sub@mail.kiz.ac.cn.
⁴² Yunnan Key Laboratory of Integrative Anthropology, Kunming, China. sub@mail.kiz.ac.cn.
⁴³ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China. sub@mail.kiz.ac.cn.

^# Contributed equally.

PMID: 40369069
DOI: 10.1038/s41586-025-08998-w

Abstract

Mainland Southeast Asia (MSEA) has rich ethnic and cultural diversity with a population of nearly 300 million^1,2. However, people from MSEA are underrepresented in the current human genomic databases. Here we present the SEA3K genome dataset (phase I), generated by deep short-read whole-genome sequencing of 3,023 individuals from 30 MSEA populations, and long-read whole-genome sequencing of 37 representative individuals. We identified 79.59 million small variants and 96,384 structural variants, among which 22.83 million small variants and 24,622 structural variants are unique to this dataset. We observed a high genetic heterogeneity across MSEA populations, reflected by the varied combinations of genetic components. We identified 44 genomic regions with strong signatures of Darwinian positive selection, covering 89 genes involved in varied physiological systems such as physical traits and immune response. Furthermore, we observed varied patterns of archaic Denisovan introgression in MSEA populations, supporting the proposal of at least two distinct instances of Denisovan admixture into modern humans in Asia³. We also detected genomic regions that suggest adaptive archaic introgressions in MSEA populations. The large number of novel genomic variants in MSEA populations highlight the necessity of studying regional populations that can help answer key questions related to prehistory, genetic adaptation and complex diseases.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

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References

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Genome diversity and signatures of natural selection in mainland Southeast Asia

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Genome diversity and signatures of natural selection in mainland Southeast Asia

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Abstract

Conflict of interest statement

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