Jun-Hun Loo

Climate Change and Postglacial Human Dispersals in Southeast Asia

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region.

Correlations in the population structure of music, genes and language

We present, to our knowledge, the first quantitative evidence that music and genes may have coevolved by demonstrating significant correlations between traditional group-level folk songs and mitochondrial DNA variation among nine indigenous populations of Taiwan. These correlations were of comparable magnitude to those between language and genes for the same populations, although music and language were not significantly correlated with one another. An examination of population structure for genetics showed stronger parallels to music than to language. Overall, the results suggest that music might have a sufficient time-depth to retrace ancient population movements and, additionally, that it might be capturing different aspects of population history than language. Music may therefore have the potential to serve as a novel marker of human migrations to complement genes, language and other markers.

Genetic affinities between the Yami tribe people of Orchid Island and the Philippine Islanders of the Batanes archipelago

BackgroundYami and Ivatan islanders are Austronesian speakers from Orchid Island and the Batanes archipelago that are located between Taiwan and the Philippines. The paternal genealogies of the Yami tribe from 1962 monograph of Wei and Liu were compared with our dataset of non-recombining Y (NRY) chromosomes from the corresponding families. Then mitochondrial DNA polymorphism was also analyzed to determine the matrilineal relationships between Yami, Ivatan, and other East Asian populations.ResultsThe family relationships inferred from the NRY Phylogeny suggested a low number of paternal founders and agreed with the genealogy of Wei and Liu (P < 0.01). Except for one Y short tandem repeat lineage (Y-STR), seen in two unrelated Yami families, no other Y-STR lineages were shared between villages, whereas mtDNA haplotypes were indiscriminately distributed throughout Orchid Island.The genetic affinity seen between Yami and Taiwanese aborigines or between Ivatan and the Philippine people was closer than that between Yami and Ivatan, suggesting that the Orchid islanders were colonized separately by their nearest neighbors and bred in isolation. However a northward gene flow to Orchid Island from the Philippines was suspected as Yami and Ivatan peoples both speak Western Malayo-Polynesian languages which are not spoken in Taiwan. Actually, only very little gene flow was observed between Yami and Ivatan or between Yami and the Philippines as indicated by the sharing of mtDNA haplogroup B4a1a4 and one O1a1* Y-STR lineage.ConclusionsThe NRY and mtDNA genetic information among Yami tribe peoples fitted well the patrilocal society model proposed by Wei and Liu. In this proposal, there were likely few genetic exchanges among Yami and the Philippine people. Trading activities may have contributed to the diffusion of Malayo-Polynesian languages among them.Finally, artifacts dating 4,000 YBP, found on Orchid Island and indicating association with the Out of Taiwan hypothesis might be related to a pioneering stage of settlement, as most dating estimates inferred from DNA variation in our data set ranged between 100-3,000 YBP.

Taiwan Y-chromosomal DNA variation and its relationship with Island Southeast Asia

BackgroundMuch of the data resolution of the haploid non-recombining Y chromosome (NRY) haplogroup O in East Asia are still rudimentary and could be an explanatory factor for current debates on the settlement history of Island Southeast Asia (ISEA). Here, 81 slowly evolving markers (mostly SNPs) and 17 Y-chromosomal short tandem repeats were used to achieve higher level molecular resolution. Our aim is to investigate if the distribution of NRY DNA variation in Taiwan and ISEA is consistent with a single pre-Neolithic expansion scenario from Southeast China to all ISEA, or if it better fits an expansion model from Taiwan (the OOT model), or whether a more complex history of settlement and dispersals throughout ISEA should be envisioned.ResultsWe examined DNA samples from 1658 individuals from Vietnam, Thailand, Fujian, Taiwan (Han, plain tribes and 14 indigenous groups), the Philippines and Indonesia. While haplogroups O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 follow a decreasing cline from Taiwan towards Western Indonesia, O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 decline northward from Western Indonesia towards Taiwan. Compared to the Taiwan plain tribe minority groups the Taiwanese Austronesian speaking groups show little genetic paternal contribution from Han. They are also characterized by low Y-chromosome diversity, thus testifying for fast drift in these populations. However, in contrast to data provided from other regions of the genome, Y-chromosome gene diversity in Taiwan mountain tribes significantly increases from North to South.ConclusionThe geographic distribution and the diversity accumulated in the O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 haplogroups on one hand, and in the O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 haplogroups on the other, support a pincer model of dispersals and gene flow from the mainland to the islands which likely started during the late upper Paleolithic, 18,000 to 15,000 years ago. The branches of the pincer contributed separately to the paternal gene pool of the Philippines and conjointly to the gene pools of Madagascar and the Solomon Islands. The North to South increase in diversity found for Taiwanese Austronesian speaking groups contrasts with observations based on mitochondrial DNA, thus hinting to a differentiated demographic history of men and women in these populations.

Ancient migration routes of Austronesian-speaking populations in oceanic Southeast Asia and Melanesia might mimic the spread of nasopharyngeal carcinoma.

Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the “Out of Africa” hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of insular Asia. The results of this analysis will be discussed using a conceptual approach.

Mitochondrial DNA association study of type 2 diabetes with or without ischemic stroke in Taiwan

BackgroundThe importance of mitochondrial DNA (mtDNA) polymorphism in the prediction of type 2 diabetes (T2D) in men and women is not well understood. We questioned whether mtDNA polymorphism, mitochondrial functions, age and gender influenced the occurrence of T2D with or without ischemic stroke (IS).MethodsWe first designed a matched case–control study of 373 T2D patients and 327 healthy unrelated individuals without history of IS. MtDNA haplogroups were determined on all participants using sequencing of the control region and relevant SNPs from the coding region. Mitochondria functional tests, systemic biochemical measurements and complete genomic mtDNA sequencing were further determined on 239 participants (73 healthy controls, 33 T2D with IS, 70 T2D only and 63 IS patients without T2D).ResultsMtDNA haplogroups B4a1a, and E2b1 showed significant association with T2D (P <0.05), and haplogroup D4 indicated resistance (P <0.05). Mitochondrial and systemic functional tests showed significantly less variance within groups bearing the same mtDNA haplotypes. There was a pronounced male excess among all T2D patients and prevalence of IS was seen only in the older population. Finally, nucleotide variant np 15746, a determinant of haplogroup G3 seen in Japanese and of B4a1a prevalent in Taiwanese was associated with T2D in both populations.ConclusionsMen appeared more susceptible to T2D than women. Although the significant association of B4a1a and E2b1 with T2D ceased when corrected for multiple testings, these haplogroups are seen only among Taiwan Aborigines, Southeast Asian and the Pacific Ocean islanders where T2D is predominant. The data further suggested that physiological and biochemical measurements were influenced by the mtDNA genetic profile of the individual. More understanding of the function of the mitochondrion in the development of T2D might indicate ways of influencing the early course of the disease.

Mitochondrial DNA Sequencing of Middle Neolithic Human Remains of Ling-Ding Site II: Implication for the Social Structure and the Origin of Northeast Coast Taiwaneses

There is a consensus that gene flow characterizing modern Mainland Chinese arrived in Taiwan during the last 400 years, mostly from East China. However, primary genetic studies of ancient human remains of the middle Neolithic era, revealing inconsistencies between the archaic genes profile and that of modern Mainland Chinese, raised debates about the time of arrival of modern Chinese in Taiwan. To resolve this problem, this study focuses on the analysis of 3000 years BP human remains excavated from the Neolithic east coast archeological Ling-Ding site II near Hualien in Taiwan. The mitochondrial DNA (mtDNA) recovered from five archeological human remains was analyzed to elucidate their genealogy, and to characterize their genetic relationship with the present-day aboriginal and non-aboriginal people of Taiwan. Five mtDNA haplogroups were characterized from the Ling-Ding site II skeletons, C4a2, N9a1, B4c1b2a, Z, and B4b. Except for mtDNA haplogroups B4c1b2a, commonly seen among the present-day central Taiwan Aborigines and scarce in the heavily sinicised Taiwan western plain tribes, all other haplogroups were common to urban Taiwanese and modern Mainland Chinese. It is proposed that a middle Neolithic gene flow, characterizing Modern Mainland East Asians, was introduced to Taiwan by settlers who reached the East coast of Taiwan in Hualien (Ling- Ding site II) and co-habited with Taiwan Mountain tribe Aborigines. The findings of this study may be relevant for the understanding of the middle Neolithic peopling of Taiwan by non-Austronesian speakers.

Modern human migrations in insular Asia according to mitochondrial DNA and non-recombining Y chromosome

Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mothers to daughters or from fathers to sons respectively. Their high polymorphism (and rate of mutation) has been used to confirm the ‘Out of Africa’ hypothesis, and to time the spread of farming by Neolithic farmers (between 8000 and 5000 years ago) from the Levant to Europe and from Mainland Southeast Asia (MSEA) to Island Southeast Asia (ISEA). Here, we first combined results obtained from sequencing of the mtDNA hyper variable regions (HVS I and II) and other relevant coding regions among 1400 individuals from ISEA, Taiwan, Fujian and MSEA (Thailand, Vietnam). Analysis of the extensive polymorphism confirmed genetic continuity, revealing very specific genetic profiles gradually changing eastward across the regions. Lineages that best represented a clade in the initial phylogeny (a branch of the genetic tree) were further analysed using complete genomic mtDNA sequencing. Finally, a most parsimonious tree was constructed. While establishing the most up to date and informative mtDNA dataset available on populations of ISEA and Taiwan, we could infer more clearly, ancient population migration routes between MSEA and ISEA. When combined with worldwide studies, the African haplogroup L3 was, as expected, the precursor to super-haplogroups M and N. We note here that M and N are the 65 000 years’ ancestors of all haplogroups seen in populations of the northern hemisphere, Australia and the New World. In genetics, inferences about the genetic makeup of the past are drawn from studies of modern-day populations. According to archaeological and linguistics studies, it is now generally accepted that Western ISEA (Sumatra, Borneo, Java, Philippines and Sulawesi) have been a very active demographic platform of expansion and dispersal of the first eastern settlers in early Palaeolithic ( 55 000– 45 000 years ago). The people who remained in the tropics are the Melanesian of today, and those who, very early, moved north, formed the east Asian populations. Some of them, much later (<10 000 years) after favourable climate changes, moved back to ISEA and even further to settle Polynesia in the Pacific and Madagascar in the Indian Ocean. The most favoured model, the ‘out of Taiwan’ was initially based on linguistic arguments, and suggests that the Austronesian-speaking populations of ISEA, Near Oceania, and Remote Oceania (the Polynesians) have a common origin among early Taiwanese agricultural groups who dispersed into ISEA 4000 years ago, reaching Near Oceania 3500 years ago [1,2]. In the process, these people completely replaced the culture (cultural diffusion) and the local populations of ISEA (demic diffusion). Interestingly, our study showed that 86% of mtDNA sequences in ISEA and Taiwan were characterized by subhaplogroups of super haplogroup M (M7b3*, M7c3c*, M7b1*, D5b3*, D6*, E*; with ‘*’ indicating all subgroups thereafter) or N (B4a1a1*, B4a2*, B4c2*, B4d1*, B5a1b*, B5a2a*, F1a1a*, F1a3*, F1a4*, F3b*). These haplogroups are not seen among the Melanesian peoples (the descendants of the palaeolithic settlers such as the Australian Aborigines and the people of Near Oceania: Papua New Guinea, Bismark archipelago), but they are predominantly seen among Austronesian-speaking groups, in Taiwan and ISEA (Philippines and Indonesia). In the Pacific and Madagascar, their mtDNA diversity was mostly restricted to mtDNA haplogroup B4a1a1 and B4a1a1a (the precursor of the Polynesian motif and the Polynesian motif). Our analysis supported that these mtDNA haplogroups had Southeast Asian origin and were therefore the result of an ancient demic and cultural diffusion. To obtain a more objective and balanced genetic viewpoint, we re-analysed all poorly defined mtDNA haplogroups using complete sequencing and also extended the analysis to the study of the paternal polymorphism obtained from slowly evolving Y single nucleotide polymorphism (Y-SNP) and the much faster evolving Y chromosome short tandem repeats (Y-STR). Interestingly, in western ISEA, migration events inferred from Y chromosome analysis generally agreed with mtDNA and also suggested some possible bidirectional population movements from Taiwan to ISEA (the out of Taiwan) or from ISEA to Taiwan. On the contrary, further eastward, migration of Austronesian speakers into the pacific ended up with populations (the Polynesians, north coast New Correspondence: Jean Trejaut, Mackay Memorial Hospital, #45 Min-Sheng Road, Tamsui 25115, Taiwan E-mail: jtrejaut@ms1.mmh.org.tw ISBT Science Series (2011) 6, 361–365