Genetic variations among four sub tribes of indigenous population (Orang Asli) from Peninsular Malaysia / Yushimah Yunus

The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, represent the minority groups which are believed to be the earliest population settled in this geographical region. They are expected to have higher level of genetic diversity due to their long history of existence as nomadic hunter-gatherer lifestyle in tropical jungle environment, may have evolved enough mutations, resulted from immerse process of natural selections and local adaptations. However, limited studies were conducted on population in Southeast Asian region especially Peninsular Malaysia. In particular the natural selection and local adaptation of the Orang Asli. In this study, the genetic architecture of individuals from four Orang Asli tribe was conducted with high-density genotyping across more than 2.5 million polymorphisms. The genome diversity and admixture between the Orang Asli tribes and with neighboring urban populations were first characterized. Subsequently the signature of positive natural selection and local adaptation using the unbiased F ST statistical analysis. Structural analysis indicate that Orang Asli formed an independent cluster from the rest of the East Asian populations. From PCA results, The Bateq and Mendriq have mixed with each other forming a Negritos group and Jakun was stayed closer to Negritos compared to Che Wong, however when the Singapore Malays (MAS) was included in the PCA, the Jakun shown to be closer with MAS whilst the Che Wong were distinct as an independent cluster suggesting a unique population history of Che Wong. The ADMIXTURE analysis result was also shown the same pattern as PCA when Orang Asli were separated from the East Asians population in K = 2. The separation between Che Wong and Jakun in K = 5 can also be observed, while K = 8 shown a unique component likely originated from the Southern China or Taiwanese aborigines. Admixture was appeared in Mendriq since they has recently undergo massive intermarriage with other populations. The three Orang Asli populations shown to had higher observed heterozygosity than expected heterozygosity and Negritos shown the higher expected heterozygosity compare to Che Wong and Jakun indicating that they have high genetic variation. Natural positive selection were detected in batch of genes associated with immune response, metabolic pathway and blood pressure. Notable examples include CDH13 in Negritos and HLA-B in Jakun and Che Wong which associated with severe malaria, two blood pressure related gene (ABCA1 and CDH13) and BTN2A1 in Jakun and Che Wong. In conclusion, by integrating genetic structure analyses and evidence of positive natural selection, the three Orang Asli populations have shown a unique genetic make-up which separated from the rest of the East Asian populations.