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The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia

Abstract

Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations—especially indigenous populations—inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N e) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000—6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration history in Southeast Asia.

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Acknowledgments

The authors would like to thank many of the group members for their helpful discussions and LetPub for its linguistic assistance during the preparation of this manuscript. We thank M. Seielstad for assistance in reviewing the manuscript and his comments. These studies were supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13040100), by the National Science Foundation of China (NSFC) grants (91331204 and 31171218). S.X. is Max-Planck Independent Research Group Leader and member of CAS Youth Innovation Promotion Association. S.X. also gratefully acknowledges the support of the National Program for Top-notch Young Innovative Talents of The “Ten-Thousand-Talents” Project and the support of K.C.Wong Education Foundation, Hong Kong. B.P.H., M.E.P. and the Malaysian investigators were supported by research grant Ministry of Science, Technology and Innovation (MOSTI) grant erBiotek Grant # 100-RM/BIOTEK 16/6/2 B (1/2011) and [100-RMI/GOV 16/6/2 (19/2011)]. B.A.Z also received funding from the following reserach grants: APEX Delivering Excellence 2012 (DE 2012) grant: (1002/PPSP/910343), USM short term grant: (304/PPSP/61311034) and MOSTI (ER-BIOTEK) grant: (304/PPSP/6150113/K105). S.W.S. was supported by the University of Toronto McLaughlin Centre and The Hospital for Sick Children Foundation. S.W.S. holds the GlaxoSmithKline-CIHR Chair in Genome Sciences at the University of Toronto and The Hospital for Sick Children. GSK has no influence on how research funding is allocated and spent. None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors have declared that no competing interests exist.

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Correspondence to Shuhua Xu.

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Deng, L., Hoh, B.P., Lu, D. et al. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia. Hum Genet 133, 1169–1185 (2014). https://doi.org/10.1007/s00439-014-1459-8

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Keywords

  • Admixture Event
  • Population Admixture
  • Autosomal SNPs
  • Malaysian Population
  • Continental Group