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.

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

“…A recent genome-wide survey using a different genotyping platform had consistently reported the positive selection of this gene in Negritos (Deng et al 2014). This candidate gene was significantly associated with severe malaria (Band et al 2012), however, its pathophysiological role is unclear hence deserved further investigation.…”

“…Majority of the population genomic studies to date have reported the European/Caucasian ancestry and HapMapbased populations (Bustamante et al 2011), with only a handful reports on East Asia (EA) and Southeast Asia (SEA) minorities (The HUGO Pan-Asian SNP Consortium 2009; Deng et al 2014;Hatin et al 2011;Liu et al 2014;Qian et al 2013;Mokhtar et al 2014). The HUGO Pan-Asian SNP Consortium revealed supportive evidence of one major inflow of human migration into Asia out of Africa, and that the Southeast Asia (SEA) was believed to be the central hub of the migration route (The HUGO PanAsian SNP Consortium 2009).…”

Analysis of Five Deep-sequenced Trio-genomes of the Peninsular Malaysia Orang Asli and North Borneo Populations

“…It is associated with blood pressure regulation, atherosclerosis protection and regulation of adiponectin level [52,53]. Interestingly, this gene was also reported to be associated with malaria susceptibility [54], and consistently exerted as a signature of positive selection in the Negrito populations from Peninsular Malaysia [17,18].…”

“…However, these native populations are largely underrepresented in the whole-genome sequencing projects. The genomic architecture of these populations were characterized by a handful of SNP-array-based genome-wide studies [17][18][19][20][21][22]. Recently, using the whole genome sequencing data of 12 unrelated individuals, we have also revealed the population structure and divergence between native populations from Peninsular Malaysia and North Borneo [23].…”

Landscape Genetics: From Classic Molecular Markers to Genomics

“…Genomic technologies have also enabled studies to uncover historical human migrations and the genetic structure and diversity of human populations. For example, a genome-wide study of Malaysian ethnic groups using a SNP array revealed that humans from the peninsular area of Malaysia had higher genetic diversity, which the authors associated with a contact zone for recent human migrations in the Asian continent [38]. Such an example suggests the association between the genetic structure of human populations with geographic variables.…”