Human Genetics

, Volume 134, Issue 4, pp 375–392 | Cite as

Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia

  • Xuanyao Liu
  • Yushimah Yunus
  • Dongsheng Lu
  • Farhang Aghakhanian
  • Woei-Yuh Saw
  • Lian Deng
  • Mohammad Ali
  • Xu Wang
  • Fadzilah Ghazali
  • Thuhairah Abdul Rahman
  • Shahrul Azlin Shaari
  • Mohd Zaki Salleh
  • Maude E. Phipps
  • Rick Twee-Hee Ong
  • Shuhua Xu
  • Yik-Ying Teo
  • Boon-Peng HohEmail author
Original Investigation


The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.


Malaria Severe Malaria Cerebral Malaria Experimental Cerebral Malaria Extended Haplotype Homozygosity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study is supported by 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)] awarded to BP Hoh and ME Phipps; and the Ministry of Education Long-term Research Grant Scheme (LRGS) funded RM34,000 for genotyping the Che Wong samples. We thank the JAKOA for their full cooperation and assistance throughout the study, the medical team from Faculty of Medicine Universiti Teknologi MARA, the Cardio-Metabolic research team at Monash University Sunway Campus, Juli Edo and Mahmood Ameen from Universiti Malaya for their involvement during sample collection, and all subjects who voluntarily participated in this study. L. P. W., R. T. H. O. and Y. Y. T. acknowledge support by the National Research Foundation, Prime Minister’s Office, Singapore under its Research Fellowship (NRF-RF-2010-05) and administered by the National University of Singapore. S. X. is Max Planck Independent Research Group Leader and member of CAS Youth Innovation Promotion Association. S. X. gratefully acknowledges support by the National Science Foundation of China (NSFC) grants (91331204 and 31171218) and the support of K. C.Wong Education Foundation, Hong Kong.

Supplementary material

439_2014_1525_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (Docx 1,694 kb)
439_2014_1525_MOESM2_ESM.docx (351 kb)
Supplementary material 2 (Docx 352 kb)
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Supplementary Table 1 Orang Asli samples information after QC (Docx 25 kb)
439_2014_1525_MOESM4_ESM.xlsx (52 kb)
Supplementary Table 2 Selection signals identified by haploPS in Negrito (Xlsx 53 kb)
439_2014_1525_MOESM5_ESM.xlsx (73 kb)
Supplementary Table 3 Selection signals identified by haploPS in Che Wong (Xlsx 74 kb)
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Supplementary Table 4 Selection signals identified by haploPS in Jakun (Xlsx  70 kb)
439_2014_1525_MOESM7_ESM.xlsx (70 kb)
Supplementary Table 5 Significant regions of positive selection in Negrito identified by iHS (Xlsx  71 kb)
439_2014_1525_MOESM8_ESM.xlsx (194 kb)
Supplementary Table 6 Significant regions of positive selection in Che Wong identified by iHS (Xlsx  194 kb)
439_2014_1525_MOESM9_ESM.xlsx (193 kb)
Supplementary Table 7 Significant regions of positive selection in Jakun identified by iHS (Xlsx  194 kb)
439_2014_1525_MOESM10_ESM.xlsx (195 kb)
Supplementary Table 8 Significant regions of positive selection in Negrito identified by FST (Xlsx  195 kb)
439_2014_1525_MOESM11_ESM.xlsx (190 kb)
Supplementary Table 9 Significant regions of positive selection in Che Wong identified by FST (Xlsx  191 kb)
439_2014_1525_MOESM12_ESM.xlsx (123 kb)
Supplementary Table 10 Significant regions of positive selection in Jakun identified by FST (Xlsx  123 kb)
439_2014_1525_MOESM13_ESM.xlsx (83 kb)
Supplementary Table 11 The top 1 % selection signals identified in Negrito by EX-EHH (Xlsx  83 kb)
439_2014_1525_MOESM14_ESM.xlsx (59 kb)
Supplementary Table 12 The top 1 % selection signals identified in Che Wong by EX-EHH (Xlsx  59 kb)
439_2014_1525_MOESM15_ESM.xlsx (65 kb)
Supplementary Table 13 The top 1 % selection signals identified in Jakun by EX-EHH (Xlsx  66 kb)
439_2014_1525_MOESM16_ESM.xlsx (65 kb)
Supplementary Table 14 The top 1 % selection signals identified by LSBL (Che Wong-Negrito-MAS) (Xlsx  66 kb)
439_2014_1525_MOESM17_ESM.docx (32 kb)
Supplementary Table 15 The top 1 % selection signals identified by LSBL (Negrito-Che Wong-MAS) (Xlsx  33 kb)
439_2014_1525_MOESM18_ESM.xlsx (53 kb)
Supplementary Table 16 The top 1 % selection signals identified by LSBL (Negrito-Jakun-MAS) (Xlsx  54 kb)
439_2014_1525_MOESM19_ESM.xlsx (45 kb)
Supplementary Table 17 The top 1 % selection signals identified by LSBL (Che Wong-Jakun-MAS) (Xlsx  45 kb)
439_2014_1525_MOESM20_ESM.xlsx (56 kb)
Supplementary Table 18 Selection signals integrated from the five metrics (Xlsx  57 kb)
439_2014_1525_MOESM21_ESM.xlsx (52 kb)
Supplementary Table 19 DAVID Gene Ontology and pathway analyses of Negrito (Xlsx  52 kb)
439_2014_1525_MOESM22_ESM.xlsx (57 kb)
Supplementary Table 20 DAVID Gene Ontology and pathway analyses of Che Wong (Xlsx  58 kb)
439_2014_1525_MOESM23_ESM.xlsx (50 kb)
Supplementary DAVID Gene Ontology and pathway analyses of Jakun (Xlsx  51 kb)
439_2014_1525_MOESM24_ESM.xlsx (47 kb)
Supplementary Table 22 Malaria related genes identified in literature (Xlsx  47 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Xuanyao Liu
    • 1
  • Yushimah Yunus
    • 2
  • Dongsheng Lu
    • 3
  • Farhang Aghakhanian
    • 4
  • Woei-Yuh Saw
    • 5
    • 6
  • Lian Deng
    • 3
  • Mohammad Ali
    • 5
  • Xu Wang
    • 6
  • Fadzilah Ghazali
    • 7
  • Thuhairah Abdul Rahman
    • 7
  • Shahrul Azlin Shaari
    • 7
  • Mohd Zaki Salleh
    • 8
  • Maude E. Phipps
    • 4
  • Rick Twee-Hee Ong
    • 6
  • Shuhua Xu
    • 3
  • Yik-Ying Teo
    • 1
    • 5
    • 6
    • 9
    • 10
  • Boon-Peng Hoh
    • 2
    Email author
  1. 1.NUS Graduate School for Integrative Science and EngineeringNational University of SingaporeSingaporeSingapore
  2. 2.Institute of Medical Molecular Biotechnology, Faculty of MedicineUniversiti Teknologi MARA, Sungai Buloh Campus, Jalan HospitalSungai BulohMalaysia
  3. 3.Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society Partner Institute for Computational BiologyShanghai Institutes for Biological Sciences, Chinese Academy of Sciences ShanghaiShanghaiChina
  4. 4.Jeffrey Cheah School of Medicine and Health SciencesMonash University Sunway CampusSubang JayaMalaysia
  5. 5.Life Sciences InstituteNational University of SingaporeSingaporeSingapore
  6. 6.Saw Swee Hock School of Public HealthNational University of SingaporeSingaporeSingapore
  7. 7.Clinical Pathology Diagnostic Centre Research Laboratory, Faculty of MedicineUniversiti Teknologi MARASungai BulohMalaysia
  8. 8.Integrative Pharmacogenomics InstituteUniversiti Teknologi MARAPuncak AlamMalaysia
  9. 9.Department of Statistics and Applied ProbabilityNational University of SingaporeSingaporeSingapore
  10. 10.Genome Institute of Singapore, Agency for ScienceTechnology and ResearchSingaporeSingapore

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