title: 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.
authors.affiliation: Max Planck Independent Research Group on Population Genomics, Chinese Academy of Sciences and Max Planck Society (CAS-MPG) Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Deng
authors.forename: Boon Peng
authors.initials: BP
authors.lastname: Hoh
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Lu
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Fu
authors.forename: Maude E
authors.initials: ME
authors.lastname: Phipps
authors.forename: Shilin
authors.initials: S
authors.lastname: Li
authors.forename: Ab Rajab
authors.initials: AR
authors.lastname: Nur-Shafawati
authors.forename: Wan Isa
authors.initials: WI
authors.lastname: Hatin
authors.forename: Endom
authors.initials: E
authors.lastname: Ismail
authors.forename: Siti Shuhada
authors.initials: SS
authors.lastname: Mokhtar
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Bin Alwi
authors.initials: BA
authors.lastname: Zilfalil
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D000222:Adaptation, Physiological; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D019143:Evolution, Molecular; D040342:Genetic Structures; D014644:Genetic Variation; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008296:Malaysia / Q000208:ethnology; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000208:ethnology / Q000235:genetics*; D013997:Time Factors