Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Agarwal A, Guindo A, Cissoko Y, Taylor JG, Coulibaly D, Kone A, Kayentao K, Djimde A, Plowe CV, Doumbo O, Wellems TE, Diallo D (2000) Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood 96:2358–2363
Alexander DH, Novembre J, Lange K (2009) Fast model-based estimation of ancestry in unrelated individuals. Genome Res 19:1655–1664. doi:10.1101/gr.094052.109
Altshuler DM, Gibbs RA, Peltonen L, Dermitzakis E, Schaffner SF, Yu F, Bonnen PE, de Bakker PI, Deloukas P, Gabriel SB, Gwilliam R, Hunt S, Inouye M, Jia X, Palotie A, Parkin M, Whittaker P, Chang K, Hawes A, Lewis LR, Ren Y, Wheeler D, Muzny DM, Barnes C, Darvishi K, Hurles M, Korn JM, Kristiansson K, Lee C, McCarrol SA, Nemesh J, Keinan A, Montgomery SB, Pollack S, Price AL, Soranzo N, Gonzaga-Jauregui C, Anttila V, Brodeur W, Daly MJ, Leslie S, McVean G, Moutsianas L, Nguyen H, Zhang Q, Ghori MJ, McGinnis R, McLaren W, Takeuchi F, Grossman SR, Shlyakhter I, Hostetter EB, Sabeti PC, Adebamowo CA, Foster MW, Gordon DR, Licinio J, Manca MC, Marshall PA, Matsuda I, Ngare D, Wang VO, Reddy D, Rotimi CN, Royal CD, Sharp RR, Zeng C, Brooks LD, McEwen JE (2010) Integrating common and rare genetic variation in diverse human populations. Nature 467:52–58. doi:10.1038/nature09298
Ang KC, Ngu MS, Reid KP, Teh MS, Aida ZS, Koh DX, Berg A, Oppenheimer S, Salleh H, Clyde MM, Md-Zain BM, Canfield VA, Cheng KC (2012) Skin color variation in Orang Asli tribes of Peninsular Malaysia. PLoS One 7:e42752. doi:10.1371/journal.pone.0042752
Baer A (1999) Health, disease and survival: a biomedical and genetic analysis of the Orang Asli of Malaysia. Center for Orang Asli Concerns, Kuala Lumpur
Baer A, Lie-Injo LE, Welch QB, Lewis AN (1976) Genetic factors and malaria in the Temuan. Am J Hum Genet 28:179–188
Band G, Le QS, Jostin L, Pirinen M, Kivinen K, Jallow M et al (2012) Imputation-based meta-analysis of severe malaria in three African populations. PLoS Genet 9(5):e1003509. doi:10.1371/journal.pgen.1003509
Barker G, Barton H, Bird M, Daly P, Datan I et al (2007) The ‘human revolution’ in lowland tropical Southeast Asia: the antiquity and behavior of anatomically modern humans at Niah Cave (Sarawak, Borneo). J Hum Evol 52:243–261
Bellwood P (2007) Prehistory of the Indo-Malaysian archipelago, 4th edn. ANU E Press, Canberra
Bidere N, Su HC, Lenardo MJ (2006) Genetic disorders of programmed cell death in the immune system. Annu Rev Immunol 24:321–352
Browning SR, Browning BL (2007) Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am J Hum Genet 81:1084–1097
Bustamante CD, Burchard EG, De La Vega FM (2011) Genomics for the world. Nature 475:163–165
Campbell MC, Tishkoff SA (2008) African Genetic Diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu Rev Genomics Hum Genet 9:403–433
Clark TG, Fry AE, Auburn S, Campino S, Diakite M, Green A, Richardson A, Teo YY, Small K, Wilson J, Jallow M, Sisay-Joof F, Pinder M, Sabeti P, Kwiatkowski DP, Rockett KA (2009) Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility. Eur J Hum Genet 17:1080–1085. doi:10.1038/ejhg.2009.8
Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K et al (2012) Novel Genetic Loci Identified for the Pathophysiology of Childhood Obesity in the Hispanic Population. PLoS One 7(12):e51954. doi:10.1371/journal.pone.0051954
Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X et al (2012) Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet 8:e1002607. doi:10.1371/journal.pgen.1002607
Delahaye NF, Coltel N, Puthier D, Barbier M, Benech P, Joly F, Iraqi FA, Grau GE, Nguyen C, Rihet P (2007) Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice. BMC Genom 8:452. doi:10.1186/1471-2164-8-452
Deng L, Hoh BP, Lu D, Fu R, Phipps ME, Li S, Nur-Shafawati AR, Hatin WI, Ismail E, Siti Shuhada M, Jin L, Zilfalil BA, Marshall CR, Scherer SW, Al-Mulla F, Shuhua XuS (2014) The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia. DOI, Huma Genetic. doi:10.1007/s00439-014-1459-8
Eng LI, Baer A, Lewis AN, Welch QB (1973) Hemoglobin Constant Spring (slow-moving hemoglobin X components) and hemoglobin e in Malayan aborigines. Am J Hum Genet 25:382–387
Faucher JF, Milama EN, Missinou MA et al (2002) The impact of malaria on common lipid parameters. Parasitol Res 88:1040–1043
Field L, Tobias R, Thomson G, Plon S (1996) Susceptibility to insulin-dependent diabetes mellitus maps to a locus (IDDM11) on human chromosome 14q24.3–q31. Genomics 33:1–8
Fox CS, Liu Y, White CC, Feitosa M, Smith AV et al (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 8(5):e1002695. doi:10.1371/journal.pgen.1002695
Franke B, Faraone SV, Asherson P, Buitelaar J, Bau CHD, Ramos-Quiroga JA, Mick E, Grevet EH, Johansson S, Haavik J et al (2012) The genetics of attention deficit/hyperactivity disorder in adults, a review. Mol Psychiatry 17:960–987
Fumagalli M, Sironi M (2014) Human genome variability, natural selection and infectious diseases. Curr Opin Immunol 30:9–16
Fumagalli M, Sironi M, Pozzoli U, Ferrer-Admettla A, Pattini L et al (2011) Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution. PLoS Genet 7(11):e1002355. doi:10.1371/journal.pgen.1002355
Hamblin MT, Di Rienzo A (2000) Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. Am J Hum Genet 66:1669–1679. doi:10.1086/302879
Hamblin MT, Thompson EE, Di Rienzo A (2002) Complex signatures of natural selection at the Duffy blood group locus. Am J Hum Genet 70:369–383. doi:10.1086/338628
Hanchard N, Elzein A, Trafford C, Rockett K, Pinder M, Jallow M, Harding R, Kwiatkowski D, McKenzie C (2007) Classical sickle beta-globin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations. BMC Genet 8:52. doi:10.1186/1471-2156-8-52
Harper K, Armelagos G (2011) The changing disease-scape in the third epidemiological transition. Int J Environ Res Public Health 7:675–697
Hatin WI, Nur-Shafawati AR, Zahri M et al (2011) Population genetic structure of Peninsular Malaysia Malay sub-ethnic groups. Plos One 6:e18312
Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J (2008) Helminth infections: the great neglected tropical diseases. J Clin Invest 118:1311–1321. doi:10.1172/JCI34261
Jakobsson M, Scholz SW, Scheet P, Gibbs JR, VanLiere JM, Fung HC, Szpiech ZA, Degnan JH, Wang K, Guerreiro R, Bras JM, Schymick JC, Hernandez DG, Traynor BJ, Simon-Sanchez J, Matarin M, Britton A, van de Leemput J, Rafferty I, Bucan M, Cann HM, Hardy JA, Rosenberg NA, Singleton AB (2008) Genotype, haplotype and copy-number variation in worldwide human populations. Nature 451:998–1003. doi:10.1038/nature06742
Jamieson SE, Miller EN, Black GF, Peacock CS, Cordell HJ, Howson JM, Shaw MA, Burgner D, Xu W, Lins-Lainson Z, Shaw JJ, Ramos F, Silveira F, Blackwell JM (2004) Evidence for a cluster of genes on chromosome 17q11-q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun 5:46–57
Jarvis JP, Scheinfeldt LB, Soi S, Lambert C, Omberg L et al (2012) Patterns of ancestry, signatures of natural selection, and genetic association with stature in western African pygmies. PLoS Genet 8(4):e1002641. doi:10.1371/journal.pgen.1002641
Jha AN, Singh VK, Kumari N, Singh A, Antony J, van Tong H, Singh S, Pati SS, Patra PK, Singh R, Toan NL, le Song H, Assaf A, Messias-Reason IJ, Velavan TP, Singh L, Thangaraj K (2012) IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations. PLoS One 7:e48136. doi:10.1371/journal.pone.0048136
Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. Am J Hum Genet 77: 171–92. doi:10.1086/432519
Kwiatkowski DP, Luoni G (2006) Host genetic factors in resistance and susceptibility to malaria. Parassitologia 48:450–467
Lee JH, Shin D-J, Park S, Kang S-M, Jang Y, Lee S-H (2013) Association between CDH13 Variants and Cardiometabolic and Vascular Phenotypes in a Korean Population. Yonsei Med J 54(6):1305–1312
Li J, Liu J, Zhao L, Ma Y, Jia M, Lu T, Ruan Y, Li Q, Yue W, Zhang D, Lifang Wang L (2013) Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry 44(2013):226–232
Liu X, Ong RT, Pillai EN, Elzein AM, Small KS, Clark TG, Kwiatkowski DP, Teo YY (2013) Detecting and characterizing genomic signatures of positive selection in global populations. Am J Hum Genet. doi:10.1016/j.ajhg.2013.04.021
Liu X, Saw W-Y, Ali M, Rick Ong T-H, Teo Y-Y (2014) Evaluating the possibility of detecting evidence of positive selection across Asia with sparse genotype data from the HUGO Pan-Asian SNP Consortium. BMC Genom 15:332
Lokossou AG, Dechavanne C, Bouraïma A, Courtin D, Le Port A, Ladékpo R, Noukpo J, Bonou D, Ahouangninou C, Sabbagh A, Fayomi B, Massougbodji A, Garcia A, Migot-Nabias F (2013) Association of IL-4 and IL-10 maternal haplotypes with immune responses to P. falciparum in mothers and newborns. BMC Infect Dis. doi: 10.1186/1471-2334-13-215
Luoni G, Verra F, Arca B, Sirima BS, Troye-Blomberg M, Coluzzi M, Kwiatkowski D, Modiano D (2001) Antimalarial antibody levels and IL4 polymorphism in the Fulani of West Africa. Genes Immun 2:411–414. doi:10.1038/sj.gene.6363797
Macaulay V, Hill C, Achilli A, Rengo C, Clarke D et al (2005) Single, rapid coastal settlement of Asia revealed by analysis of complete mitochondrial genomes. Science 308:1034–1036
Malaria Genomic Epidemiology Network (2014) Reappraisal of known malaria resistance loci in a large multicenter study: doi:10.1038/ng.2107
Mangano VD, Modiano D (2014) An evolutionary perspective of how infection drives human genome diversity: the case of malaria. Curr Opin Immunol 30:39–47
Manning AK, Hilvert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H et al (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 44:659–669
Meyer CG, Calixto Fernandes MH, Intemann CD, Kreuels B, Kobbe R, Kreuzberg C, Ayim M, Ruether A, Loag W, Ehmen C, Adjei S, Adjei O, Horstmann RD, May J (2011) IL3 variant on chromosomal region 5q31-33 and protection from recurrent malaria attacks. Hum Mol Genet 20:1173–1181. doi:10.1093/hmg/ddq562
Modiano D, Luoni G, Sirima BS, Simpore J, Verra F, Konate A, Rastrelli E, Olivieri A, Calissano C, Paganotti GM, D’Urbano L, Sanou I, Sawadogo A, Modiano G, Coluzzi M (2001) Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature 414:305–308. doi:10.1038/35104556
Mokhtar SS, Marshall CR, Phipps ME, Thiruvahindrapuram B, Lionel AC et al (2014) Novel population specific autosomal copy number variation and its functional analysis amongst negritos from Peninsular Malaysia. PLoS One 9(6):e100371. doi:10.1371/journal.pone.0100371
Nandi S, Ma L, Denis M, Karwatsky J, Li Z, Jiang XC, Zha X (2009) ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity. J Lipid Res 50:456–466
Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Brittenham G, Looareesuwan S, Clark AG, Tokunaga K (2004) Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am J Hum Genet 74:1198–1208. doi:10.1086/421330
Org E, Eyheramendy S, Juhanson P, Gieger C, Lichtner P, Klopp N et al (2009) Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two European populations. Hum Mol Genet 18:2288–2296
Panda AK, Panda M, Tripathy R, Pattanaik SS, Ravindran B, Das BK (2012) Complement receptor 1 variants confer protection from severe malaria in Odisha, India. PLoS One 7:e49420. doi:10.1371/journal.pone.0049420
Pickrell JK, Coop G, Novembre J, Kudaravalli S, Li JZ, Absher D, Srinivasan BS, Barsh GS, Myers RM, Feldman MW, Pritchard JK (2009) Signals of recent positive selection in a worldwide sample of human populations. Genome Res 19: 826–37. doi: 10.1101/gr.087577.108
Pozzoli U, Fumagalli M, Cagliani R, Comi GP, Bresolin N, Clerici M, Sironi M (2010) The role of protozoa-driven selection in shaping human genetic variability. Trends Genet 26:95–99
Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38: 904–9. doi:10.1038/ng1847
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559–75. doi:10.1086/519795
Qian W, Deng L, Lu D, Xu S (2013) Genome-wide landscapes of human local adaptation in asia. PLoS One 8:e54224
Rout R, Dhangadamajhi G, Mohapatra BN, Kar SK, Ranjit M (2011) High CR1 level and related polymorphic variants are associated with cerebral malaria in eastern-India. Infect Genet Evol 11:139–144. doi:10.1016/j.meegid.2010.09.009
Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N et al (1995) Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376:246–249. doi:10.1038/376246a0
Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X, Byrne EH, McCarroll SA, Gaudet R, Schaffner SF, Lander ES, Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, Belmont JW, Boudreau A, Hardenbol P, Leal SM, Pasternak S, Wheeler DA, Willis TD, Yu F, Yang H, Zeng C, Gao Y, Hu H, Hu W, Li C, Lin W, Liu S, Pan H, Tang X, Wang J, Wang W, Yu J, Zhang B, Zhang Q, Zhao H, Zhou J, Gabriel SB, Barry R, Blumenstiel B, Camargo A, Defelice M, Faggart M, Goyette M, Gupta S, Moore J, Nguyen H, Onofrio RC, Parkin M, Roy J, Stahl E, Winchester E, Ziaugra L, Altshuler D, Shen Y, Yao Z, Huang W, Chu X, He Y, Jin L, Liu Y, Sun W, Wang H, Wang Y, Xiong X, Xu L, Waye MM, Tsui SK, Xue H, Wong JT, Galver LM, Fan JB, Gunderson K, Murray SS, Oliphant AR, Chee MS, Montpetit A, Chagnon F, Ferretti V, Leboeuf M, Olivier JF, Phillips MS, Roumy S, Sallee C, Verner A, Hudson TJ, Kwok PY, Cai D, Koboldt DC, Miller RD, Pawlikowska L, Taillon-Miller P, Xiao M, Tsui LC et al (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449:913–918. doi:10.1038/nature06250
Sahu U, Mohapatra BN, Kar SK, Ranjit M (2013) Promoter Polymorphisms in the ATP Binding Cassette Transporter Gene Influence Production of Cell-Derived Microparticles and Are Highly Associated with Susceptibility to Severe Malaria in Humans. Infect Immun 81:1287–1294
Sambo MR, Trovoada MJ, Benchimol C, Quinhentos V, Goncalves L, Velosa R, Marques MI, Sepulveda N, Clark TG, Mustafa S, Wagner O, Coutinho A, Penha-Goncalves C (2010) Transforming growth factor beta 2 and heme oxygenase 1 genes are risk factors for the cerebral malaria syndrome in Angolan children. PLoS One 5:e11141. doi:10.1371/journal.pone.0011141
Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C et al (2011) A 2436C. A polymorphism in the human fas gene promoter associated with severe childhood malaria. PLoS Genet 7(5):e1002066. doi:10.1371/journal.pgen.1002066
Shriver MD, Kennedy GC, Parra EJ, Lawson HA, Sonpar V, Huang J, Akey JM, Jones KW (2004) The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs. Hum Genomics 1:274–286
Strasser A, Jost PJ, Nagata S (2009) The many roles of FAS receptor signaling in the immune system. Immunity 30:180–192
Stringer CB, Andrews P (1998) Genetic and fossil evidence for the origin of modern humans. Science 239:1263–1268
Takeuchi T, Adachi Y, Furihata YOM (2007) Adiponectin receptors, with special focus on the role of the third receptor, T-cadherin, in vascular disease. Med Mol Morphol 40:115–120
Teo YY, Sim X, Ong RT, Tan AK, Chen J, Tantoso E, Small KS, Ku CS, Lee EJ, Seielstad M, Chia KS (2009) Singapore Genome Variation Project: a haplotype map of three Southeast Asian populations. Genome Res 19:2154–2162. doi:10.1101/gr.095000.109
The HUGO Pan-Asian SNP Consortium (2009) Mapping human genetic diversity in Asia. Science 326:1541–1545
Vafa M, Maiga B, Berzins K, Hayano M, Bereczky S, Dolo A, Daou M, Arama C, Kouriba B, Farnert A, Doumbo OK, Troye-Blomberg M (2007) Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali. Microbes Infect 9:1043–1048. doi:10.1016/j.micinf.2007.04.011
Velez Edwards DR, Naj AC, Monda K, North KE, Neuhouser M, Magvanjav O, Kusimo I, Vitolins MZ, Manson JE, O’Sullivan MJ, Rampersaud E, Edwards TL (2012) Gene-environment interactions and obesity traits among postmenopausal African–American and Hispanic women in the Women’s Health Initiative SHARe Study. Hum Genet 132:323–336
Verbrugghe P, Bouwer S, Wiltshire S, Carter K, Chandler D, Cooper M, Morar B, Razif MFM, Henders A, Badcock JC, Dragovic M, Carr V, Almeida OP, Flicker L, Montgomery G, Jablensky A, Kalaydjieva L (2012) Impact of the reelin signaling cascade (ligands–receptors–adaptor complex) on cognition in schizophrenia. Am J Med Genet Part B 159B:392–404
Visser BJ, Wieten RW, Nagel IM, Grobusch MP (2013) Serum lipids and lipoproteins in malaria - a systematic review and meta-analysis. Malar J. 7(12):442. doi:10.1186/1475-2875-12-442
Voight BF, Kudaravalli S, Wen X, Pritchard JK (2006) A map of recent positive selection in the human genome. PLoS Biol 4:e72. doi:10.1371/journal.pbio.0040072
Wee YC, Tan KL, Kuldip K, Tai KS, George E, Tan PC, Chia P, Subramaniam R, Yap SF, Tan JA (2008) Alpha-thalassaemia in association with beta-thalassaemia patients in Malaysia: a study on the co-inheritance of both disorders. Community Genet 11:129–134. doi:10.1159/000113874
Acknowledgments
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
X. Liu and Y. Yunus contributed equally.
Electronic supplementary material
Below is the link to the electronic supplementary material.
All genomic positions in the supporting information are reported in GRCh37 coordinates.
Rights and permissions
About this article
Cite this article
Liu, X., Yunus, Y., Lu, D. et al. Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia. Hum Genet 134, 375–392 (2015). https://doi.org/10.1007/s00439-014-1525-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00439-014-1525-2