Perspectives

A key area for future work should be to identify the exact (or the closest) population as the source of admixture, as this can provide important insights on the evolutionary history of populations in general. To date, most studies only cover the major global populations in Europe and Africa, and the inclusion of native indigenous regional populations is lacking. Studies would benefit greatly from improving their global coverage of samples, particularly in Indonesia and in other populations from ISEA. Concerning ISEA, a comprehensive coverage of samples in this area would help to identify the source of local Asian ancestry in each of the unsampled populations. Borneo is understudied in Indonesian population genetic research. Almost all major local populations in Sumatra, Java, Bali, Sulawesi, Lesser Sunda Islands and Maluku have been sampled, however, Borneo has not been sampled thoroughly. In collaboration with international research institutions, I am co-leading a genomic research project in Borneo, together with Prof. Herawati Sudoyo from the Eijkman Institute for Molecular Biology, Jakarta, funded by the Indonesian Science Fund (DIPI). Starting this year, I am planning other sampling activities to cover all major ethnic and linguistic groups in Borneo. This data will generate important information on the history of human settlement in Borneo and the population structure of the indigenous Dayak people in Kalimantan: how their genetic diversity reflects that of present-day Indonesians, to reveal how people have adapted to different environments and evolved different lifestyles, continuing the works that have been done during my doctoral study (Publication list, Annex J)

Concerning the history of human settlement in Madagascar, the ancestor of the Malagasy has been pinpointed in this study. However, I only used three southern Malagasy populations as representatives of the Malagasy population, and therefore, more individuals in other Malagasy populations should be included in future studies to confirm this finding. In addition, the exact maritime routes taken during the migration events remain unknown. The inclusion of sample populations across the Indian Ocean rim, may provide information on a possible indirect route from Indonesia to eastern Africa. In this context, the inclusion of various populations on the eastern coast of Africa, such as the Swahili and Comoros, can give further insight on the Indonesian influence in the western corner of the Indian Ocean, and also on the African ancestor of the Malagasy, so concluding the scenario of human settlement in Madagascar. My current involvement in the international research projects led by Dr. François-Xavier Ricaut at the University of Toulouse (genomic and archaeological projects in Papua New Guinea and genomic project on the Swahili corridor in East Africa), will allow us to screen populations in East Africa and in the regions of eastern Indonesia and Melanesia where the Polynesian motif

possibly arose. Therefore, the aim is to determine whether the Malagasy’s genetic motif is detected outside Madagascar, to investigate the nature of its apparition and diffusion.

Sequence data

Technological advances have made whole genome sequencing from considerable number of individuals cost-effective, providing favorable circumstances to analyse data without ascertainment-bias by sampling all the variation in the genome. Inferences of demographic parameters can be estimated without modeling or correcting any ascertainment biases. Rare alleles will be observed, thus provide information about recent population structuring. In haplotype level, shared segments that contain rare alleles can give insight on ancestry signatures in admixed populations, and also to know the source of admixture. Full and more dense data on haplotype length distribution can give thorough information while modeling the demographic events such as population admixtures and its divergences, as well as its timing. Not only covering demographic questions, whole genome sequence data will also provide robust information on genetic adaptation to selective pressures and environmental changes. The international collaborative genomic projects in which I am involved, will, for the first time, explore these areas in indigenous and native populations.

Mitogenome sequences from various populations in Indonesia and eastern Africa (~800 mitogenome sequences), that were generated during the final year of my doctoral study, will be analysed further to model the settlement of populations in Indonesia. For example, the demographic history of the Ma’anyan, who has a unique genetic background, but doesn’t exhibit any admixture events, can be modeled using mitogenome sequence data in the context of the maternal lineage. In addition, mitogenome data on Malagasy populations, once available in the scientific community, will be useful to model the divergence, split, and migrations from respective Asian and African ancestral populations, to complement the results from the genome-wide SNP data presented in this dissertation.

Study of human disease and migration

The migration of large numbers of people creates opportunities for the spread and establishment of common or novel infectious diseases. There are significant inter-regional differences in geographical and climatic conditions, and indigenous people have adapted to the specific conditions and endemic diseases in their respective homelands. The role of environmental change is important in the dissemination of infectious diseases, and when

people migrate they also bring pathogens from their specific regions. Studying various diseases as population history and migration markers can be a complement to general population genetics / molecular anthropology studies, to gain a holistic view on where populations originated, where people migrate, and how people have adapted to their old and new environments. Traces of infectious disease parasites and their vectors can bring an understanding, not only of adaptation mechanisms against diseases, but also on the routes taken by humans during their global migrations.

Studies of adaptation to malaria have shown that populations have unique regional-level genetic profiles to counter malaria infection, such as sickle cell anemia and Duffy negativity in western Africa, Hemoglobin E (HbE) and Southeast Asian Ovalocytosis (SAO) in Southeast Asia, and alpha and beta Thalassaemia and G6PD deficiency which have different genotypes in different populations across the world. Research by Rabe et al. (2002) on several villages in the highlands of central Madagascar have shown a small percentage of SAO presence. Further surveys of SAO presence throughout Madagascar, and determining the presence of the SLC4A1 gene haplotype around the SAO-deletion region, can give additional supporting evidence of an Indonesian influence in Madagascar. Studies detecting SAO presence in Indonesian and eastern African populations is currently in progress. In addition, other unique Indonesian genotypes for molecular adaptation against malaria, as mentioned, will also be investigated in the future.

I have started a collaboration with the Pasteur Institute in Paris, to study the distribution of HTLV-1 and HHV-8 viruses in Indonesia. These viruses have wide distributions in Oceania and East Asia, but no studies have been conducted in Indonesia in the context of it being a focal crossroad in human migration from East Asia into Oceania. Traces of these viruses must be present in Indonesia. This study will bring new understanding on HTLV-1 and HHV-8 genotype diversity, and will also complement the scenario of Austronesian eastward dispersal into the Pacific.