Whole-genome sequencing reveals Yunnan as the crossroads of East and Southeast Asia for human gene flow

Xiaobo Qian; Bo Li; Jianmei Liu; Yushan Huang; Wenxi Gu; Yuwen Zhou; Qiong Nan; Chao Wang; Le Cheng; Junkun Niu; Fengrui Zhang; Qian Li; Xiuqing Zhang; Jinlong Yang; Yinglei Miao; Mingyan Fang; Xin Jin; Yang Sun

doi:10.1016/j.jgg.2026.01.003

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Whole-genome sequencing reveals Yunnan as the crossroads of East and Southeast Asia for human gene flow

doi: 10.1016/j.jgg.2026.01.003

a. College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
b. BGI Research, Wuhan, Hubei 430074, China;
c. Department of Geriatric Medical Center, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;
d. MGI Tech, Shenzhen, Guangdong 518083, China;
e. BGI Research, Shenzhen, Guangdong 518083, China;
f. BGI Genomics, Shenzhen, Guangdong 518083, China;
g. School of Basic Medical Sciences, Dali University, Dali, Yunnan 671000, China;
h. Clinical Pharmacy, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;
i. College of Forensic Sciences, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China;
j. State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, Guangdong 518083, China;
k. School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, China;
l. School of Medicine, South China University of Technology, Guangzhou, 510006 Guangdong, China;
m. Shenzhen Key Laboratory of Transomics Biotechnologies, BGI Research, Shenzhen, Guangdong 518083, China

Funds:

We sincerely thank all the volunteers who agreed to contribute blood samples and participate in this study. We thank T. L. for their involvement during sampling collection. We acknowledge X.Z., Q.F., T.W., F.B., Y.Z., and J.C. for their helpful discussions and comments on the manuscript. This work was supported by the National Key R&

D Program of China (2024YFA1308300), the National Natural Science Foundation of China (82460112), the “Xingdian Talents" Support Project of Yunnan Province (RLQB20220006), Yunnan Fundamental Research Projects (202501AS070031), the Yunnan Provincial Key Research and Development Plan (202403AC100020), the Innovative Team of Yunnan Province (202305AS350019), the Yunnan High-level Talent Training Support Program: special project for industrial technology leading talents (2021, Yunnan Development and Reform Commission), the Technology Innovation and Talent Cultivation Project of Yunnan Province (202105AD160064), and grants from Shenzhen Science and Technology Program (SYSPG20241211173852024). The funders had no role in the study design, data collection, analysis, the decision to publish, or the preparation of the manuscript.

Received Date: 2025-02-06
Accepted Date: 2026-01-07
Rev Recd Date: 2026-01-05

Available Online: 2026-01-13

Abstract

Abstract

Yunnan Province has long served as a key nexus facilitating economic and cultural exchanges between East Asia, Southeast Asia, and Qinghai-Tibet Plateau. However, previous genetic studies were largely limited by sparse marker density, low sequencing depth, or single-population designs, leaving the population genetic structure and demographic history insufficiently resolved. Here, we conduct a high-resolution population genetic study based on 366 high-depth whole-genome sequencing samples from six ethnic groups, including Bai, Dai, Hani, Miao, Tibetan, and Han. We identify approximately 3.51 million novel variants and reveal fine-scale population structure and complex demographic histories among Yunnan ethnic groups. Beyond the three ancestries proposed by the tri-genealogy hypothesis, we detect a Han Chinese-related lineage, Yan-Huang, within multiple Yunnan populations. We further demonstrate that Yunnan represents a major gene-flow hotspot across East and Southeast Asia despite geographic barriers. Finally, we identify genomic loci under positive selection with candidate genes enriched in immune regulation, energy metabolism, cardiac development, and dietary adaptation, highlighting the role of local environmental pressures in shaping the genetic diversity of Yunnan populations.
- Yunnan populations,
- Whole-genome sequencing,
- Population structure,
- Demographic history,
- Gene flow,
- Positive selection

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