Unique characteristics of the Ainu population in Northern Japan

Various genetic data (classic markers, mitochondrial DNAs, Y chromosomes and genome-wide single-nucleotide polymorphisms (SNPs)) have confirmed the coexistence of three major human populations on the Japanese Archipelago: Ainu in Hokkaido, Ryukyuans in the Southern Islands and Mainland Japanese. We compared genome-wide SNP data of the Ainu, Ryukyuans and Mainland Japanese, and found the following results: (1) the Ainu are genetically different from Mainland Japanese living in Tohoku, the northern part of Honshu Island; (2) using Ainu as descendants of the Jomon people and continental Asians (Han Chinese, Koreans) as descendants of Yayoi people, the proportion of Jomon genetic component in Mainland Japanese was ~ 18% and ~ 28% in Ryukyuans; (3) the time since admixture for Mainland Japanese ranged from 55 to 58 generations ago, and 43 to 44 generations ago for the Ryukyuans, depending on the number of Ainu individuals with varying rates of recent admixture with Mainland Japanese; (4) estimated haplotypes of some Ainu individuals suggested relatively long-term admixture with Mainland Japanese; and (5) highly differentiated genomic regions between Ainu and Mainland Japanese included EDAR and COL7A1 gene regions, which were shown to influence macroscopic phenotypes. These results clearly demonstrate the unique status of the Ainu and Ryukyuan people within East Asia

A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan

The Jomon period of the Japanese Archipelago, characterized by cord-marked ‘jomon’ potteries, has yielded abundant human skeletal remains. However, the genetic origins of the Jomon people and their relationships with modern populations have not been clarified. We determined a total of 115 million base pair nuclear genome sequences from two Jomon individuals (male and female each) from the Sanganji Shell Mound (dated 3000 years before present) with the Jomon-characteristic mitochondrial DNA haplogroup N9b, and compared these nuclear genome sequences with those of worldwide populations. We found that the Jomon population lineage is best considered to have diverged before diversification of present-day East Eurasian populations, with no evidence of gene flow events between the Jomon and other continental populations. This suggests that the Sanganji Jomon people descended from an early phase of population dispersals in East Asia. We also estimated that the modern mainland Japanese inherited <20% of Jomon peoples’ genomes. Our findings, based on the first analysis of Jomon nuclear genome sequence data, firmly demonstrate that the modern mainland Japanese resulted from genetic admixture of the indigenous Jomon people and later migrants

Cranio-morphometric and aDNA corroboration of the Austronesian dispersal model in ancient Island Southeast Asia: Support from Gua Harimau, Indonesia

The Austronesian language is spread from Madagascar in the west, Island Southeast Asia (ISEA) in the east (e.g. the Philippines and Indonesian archipelagoes) and throughout the Pacific, as far east as Easter Island. While it seems clear that the remote ancestors of Austronesian speakers originated in Southern China, and migrated to Taiwan with the development of rice farming by c. 5500 BP and onto the northern Philippines by c. 4000 BP (the Austronesian Dispersal Hypothesis or ADH), we know very little about the origins and emergence of Austronesian speakers in the Indonesian Archipelago. Using a combination of cranial morphometric and ancient mtDNA analyses on a new dataset from Gua Hairmau, that spans the pre-Neolithic through to Metal Period (5712—5591cal BP to 1864—1719 cal BP), we rigorously test the validity of the ADH in ISEA. A morphometric analysis of 23 adult male crania, using 16 of Martin’s standard measurements, was carried out with results compared to an East and Southeast Asian dataset of 30 sample populations spanning the Late Pleistocene through to Metal Period, in addition to 39 modern samples from East and Southeast Asia, near Oceania and Australia. Further, 20 samples were analyzed for ancient mtDNA and assigned to identified haplogroups. We demonstrate that the archaeological human remains from Gua Harimau cave, Sumatra, Indonesia provide clear evidence for at least two (cranio-morphometrically defined) and perhaps even three (in the context of the ancient mtDNA results) distinct populations from two separate time periods. The results of these analyses provide substantive support for the ADH model in explaining the origins and population history of ISEA peoples.This study was supported in part by JSPS KAKENHI Grant No. 23247040 and No. 16H02527 to HM and Australian Research Council Grant No. FT120100299 to MFO and DP150104458 to HCH

Genomic Insights into the Formation of Human Populations in East Asia

厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室王传超教授课题组与哈佛医学院David Reich教授团队合作，联合全球43个单位的85位共同作者组成的国际合作团队通过古DNA精细解析东亚人群形成历史。研究人员利用古DNA数据检验了东亚地区农业和语言共扩散理论，综合考古学、语言学等证据，该研究系统性地重构了东亚人群的形成、迁徙和混合历史。这是目前国内开展的东亚地区最大规模的考古基因组学研究，此次所报道的东亚地区古人基因组样本量是以往国内研究机构所发表的样本量总和的两倍，改变了东亚地区尤其是中国境内考古基因组学研究长期滞后的局面。 该研究是由王传超教授团队与哈佛医学院（David Reich教授）、德国马普人类历史科学研究所（Johannes Krause教授）、复旦大学现代人类学教育部重点实验室（李辉教授和金力院士）、维也纳大学进化人类学系（Ron Pinhasi副教授）、南洋理工大学人文学院（Hui-Yuan Yeh助理教授）、俄罗斯远东联邦大学科学博物馆（Alexander N Popov研究员）、西安交通大学（张虎勤教授）、蒙古国国家博物馆研究中心、乌兰巴托国立大学考古系、华盛顿大学人类学系、台湾成功大学考古所、加州大学人类学系等全球43个单位的85位共同作者组成的国际合作团队联合完成的。厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室为论文第一完成单位。厦门大学人类学研究所韦兰海副教授、胡荣助理教授、郭健新博士后、何光林博士后和杨晓敏硕士参与了研究工作。The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people1,2. We report genome-wide data from 166 East Asians dating to 6000 BCE-1000 CE and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan plateau are linked by a deeply-splitting lineage likely reflecting a Late Pleistocene coastal migration. We follow Holocene expansions from four regions. First, hunter-gatherers of Mongolia and the Amur River Basin have ancestry shared by Mongolic and Tungusic language speakers but do not carry West Liao River farmer ancestry contradicting theories that their expansion spread these proto-languages. Second, Yellow River Basin farmers at ～3000 BCE likely spread Sino-Tibetan languages as their ancestry dispersed both to Tibet where it forms up ～84% to some groups and to the Central Plain where it contributed ～59-84% to Han Chinese. Third, people from Taiwan ～1300 BCE to 800 CE derived ～75% ancestry from a lineage also common in modern Austronesian, Tai-Kadai and Austroasiatic speakers likely deriving from Yangtze River Valley farmers; ancient Taiwan people also derived ～25% ancestry from a northern lineage related to but different from Yellow River farmers implying an additional north-to-south expansion. Fourth, Yamnaya Steppe pastoralist ancestry arrived in western Mongolia after ～3000 BCE but was displaced by previously established lineages even while it persisted in western China as expected if it spread the ancestor of Tocharian Indo-European languages. Two later gene flows affected western Mongolia: after ～2000 BCE migrants with Yamnaya and European farmer ancestry, and episodic impacts of later groups with ancestry from Turan.We thank David Anthony, Ofer Bar-Yosef, Katherine Brunson, Rowan Flad, Pavel Flegontov,Qiaomei Fu, Wolfgang Haak, Iosif Lazaridis, Mark Lipson, Iain Mathieson, Richard Meadow,Inigo Olalde, Nick Patterson, Pontus Skoglund, Dan Xu, and the four reviewers for valuable comments. We thank Naruya Saitou and the Asian DNA Repository Consortium for sharing genotype data from present-day Japanese groups. We thank Toyohiro Nishimoto and Takashi Fujisawa from the Rebun Town Board of Education for sharing the Funadomari Jomon samples, and Hideyo Tanaka and Watru Nagahara from the Archeological Center of Chiba City who are excavators of the Rokutsu Jomon site. The excavations at Boisman-2 site (Boisman culture), the Pospelovo-1 site (Yankovsky culture), and the Roshino-4 site (Heishui Mohe culture) were funded by the Far Eastern Federal University and the Institute of History,Archaeology and Ethnology Far Eastern Branch of the Russian Academy of Sciences; research on Pospelovo-1 is funded by RFBR project number 18-09-40101. C.C.W was funded by the Max Planck Society, the National Natural Science Foundation of China (NSFC 31801040), the Nanqiang Outstanding Young Talents Program of Xiamen University (X2123302), the Major project of National Social Science Foundation of China (20&ZD248), a European Research Council (ERC) grant to Dan Xu (ERC-2019-ADG-883700-TRAM) and Fundamental Research Funds for the Central Universities (ZK1144). O.B. and Y.B. were funded by Russian Scientific Foundation grant 17-14-01345. H.M. was supported by the grant JSPS 16H02527. M.R. and C.C.W received funding from the ERC under the European Union’s Horizon 2020 research and innovation program (grant No 646612) to M.R. The research of C.S. is supported 30 by the Calleva Foundation and the Human Origins Research Fund. H.L was funded NSFC (91731303, 31671297), B&R International Joint Laboratory of Eurasian Anthropology (18490750300). J.K. was funded by DFG grant KR 4015/1-1, the Baden Württemberg Foundation, and the Max Planck Institute. Accelerator Mass Spectrometry radiocarbon dating work was supported by the National Science Foundation (NSF) (BCS-1460369) to D.J.K. and B.J.C. D.R. was funded by NSF grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul M. Allen Frontiers Group, John Templeton Foundation grant 61220, a gift from Jean-Francois Clin, and the Howard Hughes Medical Institute. 该研究得到了国家自然科学基金“中国东南各族群的遗传混合”、国家社科基金重大项目“多学科视角下的南岛语族的起源和形成研究”、厦门大学南强青年拔尖人才支持计划A类、中央高校基本科研业务费等资助

Human genetic diversity in the Japanese Archipelago: dual structure and beyond

The Japanese Archipelago stretches approximately 3,000 kilometers from Hokkaido in the north to the Ryukyu Islands in the south, and has seen human activity since at least 30 thousand years ago (KYA). The Jomon period from 16 to 3 KYA is associated with cord-marked pottery and the people at that time, who were hunter-gatherers, occupied a range of locations across the Japanese Archipelago. The Yayoi period from 3 to 1.7 KYA saw the introduction of migrants from the Asian Continent who brought rice agriculture to the archipelago. The dual-structure model, which is based on craniofacial measurements, proposes that admixture between the Jomon and Yayoi people resulted in current-day Japanese. Subsequent genetic studies using uniparental and autosomal markers in currentday and ancient human samples are widely in support of the dual-structure model. These genetic data have also unveiled the uniqueness of the indigenous Ainu and Ryukyuan people while further demonstrating the genetic substructure within the Mainland Japanese

Evolutionary History of the Risk of SNPs for Diffuse-Type Gastric Cancer in the Japanese Population

A genome wide association study reported that the T allele of rs2294008 in a cancer-related gene, PSCA, is a risk allele for diffuse-type gastric cancer. This allele has the highest frequency (0.63) in Japanese in Tokyo (JPT) among 26 populations in the 1000 Genomes Project database. FST &asymp; 0.26 at this single nucleotide polymorphism is one of the highest between JPT and the genetically close Han Chinese in Beijing (CHB). To understand the evolutionary history of the alleles in PSCA, we addressed: (i) whether the C non-risk allele at rs2294008 is under positive selection, and (ii) why the mainland Japanese population has a higher T allele frequency than other populations. We found that haplotypes harboring the C allele are composed of two subhaplotypes. We detected that positive selection on both subhaplotypes has occurred in the East Asian lineage. However, the selection on one of the subhaplotypes in JPT seems to have been relaxed or ceased after divergence from the continental population; this may have caused the elevation of T allele frequency. Based on simulations under the dual structure model (a specific demography for the Japanese) and phylogenetic analysis with ancient DNA, the T allele at rs2294008 might have had high frequency in the Jomon people (one of the ancestral populations of the modern Japanese); this may explain the high T allele frequency in the extant Japanese

A highly efficient scheme for library preparation from single-stranded DNA

Abstract Although methods for sequencing library preparation from double-stranded DNA are well established, those from single-stranded DNA (ssDNA) have not been well studied. Further, the existing methods have limitations in efficiency and yield. Therefore, we developed a highly efficient procedure for sequencing library preparation from ssDNA. In this method, the first adaptor tagging of ssDNA is performed using terminal deoxyribonucleotidyl transferase (TdT)-assisted adenylate connector-mediated ssDNA (TACS) ligation, which we reported recently. After complementary strand synthesis using the adaptor-tagged ssDNA, second adaptor tagging via Vaccinia virus topoisomerase I (VTopoI or TOPO)-based adaptor ligation is performed. With additional steps for degradation, repression, and removal of the adaptor dimer, the proposed TACS-TOPO scheme realizes adaptor dimer-free sequencing library preparation from ssDNA samples of 24 pg. The TACS-TOPO scheme was successfully applied to cell-free DNA analysis with amplification-free library preparation from 50 µL of human serum. A modified TACS-TOPO scheme was also applied to DNA extracted from ancient human bones, bringing two to eight times more library yields than those using a conventional library preparation protocol. The procedures for preparing VTopoI and its complex with a double-stranded oligonucleotide adaptor are also described. Overall, the proposed TACS-TOPO scheme can facilitate practical and sensitive sequencing analysis of ssDNA

Late Jomon male and female genome sequences from the Funadomari site in Hokkaido, Japan

The Funadomari Jomon people were hunter-gatherers living on Rebun Island, Hokkaido, Japan c. 3500–3800 years ago. In this study, we determined the high-depth and low-depth nuclear genome sequences from a Funadomari Jomon female (F23) and male (F5), respectively. We genotyped the nuclear DNA of F23 and determined the human leukocyte antigen (HLA) class-I genotypes and the phenotypic traits. Moreover, a pathogenic mutation in the CPT1A gene was identified in both F23 and F5. The mutation provides metabolic advantages for consumption of a high-fat diet, and its allele frequency is more than 70% in Arctic populations, but is absent elsewhere. This variant may be related to the lifestyle of the Funadomari Jomon people, who fished and hunted land and marine animals. We observed high homozygosity by descent (HBD) in F23, but HBD tracts longer than 10 cM were very limited, suggesting that the population size of Northern Jomon populations were small. Our analysis suggested that population size of the Jomon people started to decrease c. 50000 years ago. The phylogenetic relationship among F23, modern/ancient Eurasians, and Native Americans showed a deep divergence of F23 in East Eurasia, probably before the split of the ancestor of Native Americans from East Eurasians, but after the split of 40000-year-old Tianyuan, indicating that the Northern Jomon people were genetically isolated from continental East Eurasians for a long period. Intriguingly, we found that modern Japanese as well as Ulchi, Korean, aboriginal Taiwanese, and Philippine populations were genetically closer to F23 than to Han Chinese. Moreover, the Y chromosome of F5 belonged to haplogroup D1b2b, which is rare in modern Japanese populations. These findings provided insights into the history and reconstructions of the ancient human population structures in East Eurasia, and the F23 genome data can be considered as the Jomon Reference Genome for future studies