Genetic studies of human diversity in East Asia

East Asia is one of the most important regions for studying evolution and genetic diversity of human populations. Recognizing the relevance of characterizing the genetic diversity and structure of East Asian populations for understanding their genetic history and designing and interpreting genetic studies of human diseases, in recent years researchers in China have made substantial efforts to collect samples and generate data especially for markers on Y chromosomes and mtDNA. The hallmark of these efforts is the discovery and confirmation of consistent distinction between northern and southern East Asian populations at genetic markers across the genome. With the confirmation of an African origin for East Asian populations and the observation of a dominating impact of the gene flow entering East Asia from the south in early human settlement, interpretation of the north-south division in this context poses the challenge to the field. Other areas of interest that have been studied include the gene flow between East Asia and its neighbouring regions (i.e. Central Asia, the Sub-continent, America and the Pacific Islands), the origin of Sino-Tibetan populations and expansion of the Chinese.     

Challenging views on the peopling history of East Asia: the story according to HLA markers

The peopling of East Asia by the first modern humans is strongly debated from a genetic point of view. A north-south genetic differentiation observed in this geographic area suggests different hypotheses on the origin of Northern East Asian (NEA) and Southern East Asian (SEA) populations. In this study, the highly polymorphic HLA markers were used to investigate East Asian genetic diversity. Our database covers a total of about 127,000 individuals belonging to 84 distinct Asian populations tested for HLA-A, -B, -C, -DPB1, and/or -DRB1 alleles. Many Chinese populations are represented, which have been sampled in the last 30 years but rarely taken into account in international research due to their data published in Chinese. By using different statistical methods, we found a significant correlation between genetics and geography and relevant genetic clines in East Asia. Additionally, HLA alleles appear to be unevenly distributed: some alleles observed in NEA populations are widespread at the global level, while some alleles observed in SEA populations are virtually unique in Asia. The HLA genetic variation in East Asia is also characterized by a decrease of diversity from north to south, although a reverse pattern appears when one only focuses on alleles restricted to Asia. These results reflect a more complex migration history than that illustrated by the "southern-origin" hypothesis, as genetic contribution of ancient human migrations through a northern route has probably been quite substantial. We thus suggest a new overlapping model where northward and southward opposite migrations occurring at different periods overlapped.     

遗传学视角下东亚人群的起源和演化

东亚是研究解剖学意义上现代人迁徙和演化的重要地带之一,该地区现代人群的起源及形成问题一直都是人类学领域广泛关注的焦点。遗传学研究为重建东亚人群历史提供了新的视角和见解。越来越多的遗传学证据表明,现代人约20万年前起源于非洲的晚期智人,并于10万年前走出非洲,大约在5~6万年前沿海岸线快速到达东亚南部,进而扩散到整个东亚地区。早期智人可能对走出非洲的现代人有一定程度的遗传贡献。早期定居、文化同化、人群迁徙以及基因交流等,对东亚人群的起源和演化起着至关重要的作用。前期的研究对东亚人群的源流历史进行了细致的分析,很大程度上解决了考古学、历史学等领域长期以来存在的分歧,然而这还需通过全基因组学和古DNA研究的进一步验证。本文从遗传学视角梳理和总结了东亚人群起源、迁徙和演化的历史,完善了对东亚人群演变的系统认识,并对未来东亚人群源流历史研究的发展方向做了展望。     

Y-chromosome evidence of southern origin of the East Asian-specific haplogroup O3-M122

The prehistoric peopling of East Asia by modern humans remains controversial with respect to early population migrations. Here, we present a systematic sampling and genetic screening of an East Asian-specific Y-chromosome haplogroup (O3-M122) in 2,332 individuals from diverse East Asian populations. Our results indicate that the O3-M122 lineage is dominant in East Asian populations, with an average frequency of 44.3%. The microsatellite data show that the O3-M122 haplotypes in southern East Asia are more diverse than those in northern East Asia, suggesting a southern origin of the O3-M122 mutation. It was estimated that the early northward migration of the O3-M122 lineages in East Asia occurred approximately 25,000-30,000 years ago, consistent with the fossil records of modern humans in East Asia.     

云南bo人源流的父系和母系遗传研究

对云南人32份男性DNA样本进行Y染色体单倍型以及mitochondrialDNA(mtDNA)单倍型分析,结果发现云南人的父系和母系遗传组分都表现出典型的南方人群的遗传特征。由人的数据结合已经发表的东亚人群的Y染色体和mtDNA单倍型(haplotype)数据进行MultidimensionalScaling(MDS)分析,结果表明,在MDS分布图中人群体的Y染色体单倍型和mtDNA单倍型都与南方人群聚在一起。这一结果支持人的遗传族源为东亚南方人群后裔,与考古学的推论相一致。结合历史和考古学证据来探讨人的起源和史前迁移,为揭开“人悬棺”这种独特的考古文化的起源和史前传播提供遗传学的研究证据。     

On the origin of mongrels: evolutionary history of free-breeding dogs in Eurasia

Although a large part of the global domestic dog population is free-ranging and free-breeding, knowledge of genetic diversity in these free-breeding dogs (FBDs) and their ancestry relations to pure-breed dogs is limited, and the indigenous status of FBDs in Asia is still uncertain. We analyse genome-wide SNP variability of FBDs across Eurasia, and show that they display weak genetic structure and are genetically distinct from pure-breed dogs rather than constituting an admixture of breeds. Our results suggest that modern European breeds originated locally from European FBDs. East Asian and Arctic breeds show closest affinity to East Asian FBDs, and they both represent the earliest branching lineages in the phylogeny of extant Eurasian dogs. Our biogeographic reconstruction of ancestral distributions indicates a gradual westward expansion of East Asian indigenous dogs to the Middle East and Europe through Central and West Asia, providing evidence for a major expansion that shaped the patterns of genetic differentiation in modern dogs. This expansion was probably secondary and could have led to the replacement of earlier resident populations in Western Eurasia. This could explain why earlier studies based on modern DNA suggest East Asia as the region of dog origin, while ancient DNA and archaeological data point to Western Eurasia.     

Deep History of East Asian Populations Revealed Through Genetic Analysis of the Ainu

Despite recent advances in population genomics, much remains to be elucidated with regard to East Asian population history. The Ainu, a hunter–gatherer population of northern Japan and Sakhalin island of Russia, are thought to be key to elucidating the prehistory of Japan and the peopling of East Asia. Here, we study the genetic relationship of the Ainu with other East Asian and Siberian populations outside the Japanese archipelago using genome-wide genotyping data. We find that the Ainu represent a deep branch of East Asian diversity more basal than all present-day East Asian farmers. However, we did not find a genetic connection between the Ainu and populations of the Tibetan plateau, rejecting their long-held hypothetical connection based on Y chromosome data. Unlike all other East Asian populations investigated, the Ainu have a closer genetic relationship with northeast Siberians than with central Siberians, suggesting ancient connections among populations around the Sea of Okhotsk. We also detect a recent genetic contribution of the Ainu to nearby populations, but no evidence for reciprocal recent gene flow is observed. Whole genome sequencing of contemporary and ancient Ainu individuals will be helpful to understand the details of the deep history of East Asians.     

Genetic variability,local selection and demographic history: genomic evidence of evolving towards allopatric speciation in Asian seabass

Genomewide analysis of genetic divergence is critically important in understanding the genetic processes of allopatric speciation. We sequenced RAD tags of 131 Asian seabass individuals of six populations from South‐East Asia and Australia/Papua New Guinea. Using 32 433 SNPs, we examined the genetic diversity and patterns of population differentiation across all the populations. We found significant evidence of genetic heterogeneity between South‐East Asian and Australian/Papua New Guinean populations. The Australian/Papua New Guinean populations showed a rather lower level of genetic diversity. F_ST and principal components analysis revealed striking divergence between South‐East Asian and Australian/Papua New Guinean populations. Interestingly, no evidence of contemporary gene flow was observed. The demographic history was further tested based on the folded joint site frequency spectrum. The scenario of ancient migration with historical population size changes was suggested to be the best fit model to explain the genetic divergence of Asian seabass between South‐East Asia and Australia/Papua New Guinea. This scenario also revealed that Australian/Papua New Guinean populations were founded by ancestors from South‐East Asia during mid‐Pleistocene and were completely isolated from the ancestral population after the last glacial retreat. We also detected footprints of local selection, which might be related to differential ecological adaptation. The ancient gene flow was examined and deemed likely insufficient to counteract the genetic differentiation caused by genetic drift. The observed genomic pattern of divergence conflicted with the ‘genomic islands’ scenario. Altogether, Asian seabass have likely been evolving towards allopatric speciation since the split from the ancestral population during mid‐Pleistocene.     

East Asian contributions to Dutch traditional and western commercial chickens inferred from mtDNA analysis

Understanding the complex origin of domesticated populations is of vital importance for understanding, preserving and exploiting breed genetic diversity. Here, we aim to assess Asian contributions to European traditional breeds and western commercial chickens for mitochondrial genetic diversity. To this end, a 365‐bp fragment of the chicken mtDNA D‐loop region of 16 Dutch fancy breeds (113 individuals) was surveyed, comprising almost the entire breed diversity of The Netherlands. We also sequenced the same fragment for 160 commercial birds representing all important commercial types from multiple commercial companies that together represent more than 50% of the worldwide commercial value. We identified 20 different haplotypes. The haplotypes clustered into five clades. The commonest clade (E‐clade) supposedly originates from the Indian subcontinent. In addition, both in commercial chicken and Dutch fancy breeds, many haplotypes were found with a clear East Asian origin. However, the erratic occurrence of many different East Asian mitochondrial clades indicates that there were many independent instances where breeders used imported exotic chickens for enhancing local breeds. Nucleotide diversity and haplotype diversity analyses showed the influence of the introgression of East Asian chicken on genetic diversity. All populations that had haplotypes of multiple origin displayed high inferred diversity, as opposed to most populations that had only a single mitochondrial haplotype signature. Most fancy breeds were found to have a much lower within‐population diversity compared to broilers and layers, although this is not the case for mitochondrial estimates in fancy breeds that have multiple origin haplotypes.     

STR Polymorphism in Indigenous Daghestan Populations

Genomic diversity of 21 STR loci has been studied in six ethnic populations of Daghestan (the Caucasus), namely, Avars, Dargins, Kubachians, Lezgins, Kumiks, and Nogais, and the results have been compared with these data for European, African, and East Asian ethnic groups. Daghestan is unique in its ethnic diversity, which is the greatest in the Caucasus: 26 out of approximately 50 autochthonous ethnic groups of the Caucasus live there. The genetic origin of this wide ethnic diversity of Daghestan and the Caucasus as a whole is still obscure. The genetic heterogeneity of Daghestan populations has been found to be lower than that of most other populations in the world. This is explained by a prolonged isolation and gene drift in their demographic history. Generalized genetic distances between ethnic groups calculated for the whole set of loci studied allow differentiating Asian populations from African ones, with European populations occupying intermediate positions. All Daghestan ethnic populations form a distinct common group together with some European populations (Finnish, Polish, and French). Nogais are genetically close to Southeast Asian populations. The genetic closeness and the apparently equal genetic diversity of Daghestan and European populations suggest that the ethnic differentiation of the ancestral populations of Daghestan and European ethnic groups occurred in the earliest populations of modern humans.     

STR polymorphism in populations of indigenous Daghestan ethnic groups

Genomic diversity of 21 STR loci has been studied in six ethnic populations of Daghestan (the Caucasus), namely, Avars, Dargins, Kubachians, Lezgins, and Nogais, and the results have been compared with these data for European, African, and East Asian ethnic groups. Daghestan is unique in its ethnic diversity, which is the greatest in the Caucasus: 26 out of approximately 50 autochthonous ethnic groups of the Caucasus live there. The genetic origin of this wide ethnic diversity of Daghestan and the Caucasus as a whole is still obscure. The genetic heterogeneity of Daghestan populations has been found to be lower than that of most other populations in the world. This is explained by a prolonged isolation and gene drift in their demographic history. Generalized genetic distances between ethnic groups calculated for the whole set of loci studied allow differentiating Asian populations from African ones, with European populations occupying intermediate positions. All Daghestan ethnic populations form a distinct common group together with some European populations (Finnish, Polish, and French). Nogais are genetically close to Southeast Asian populations. The genetic closeness and the apparently equal genetic diversity of Daghestan and European populations suggest that the ethnic differentiation of the ancestral populations of Daghestan and European ethnic groups occurred in the earliest populations of modern humans.     

Human migration through bottlenecks from Southeast Asia into East Asia during Last Glacial Maximum revealed by Y chromosomes

Molecular anthropological studies of the populations in and around East Asia have resulted in the discovery that most of the Y-chromosome lineages of East Asians came from Southeast Asia. However, very few Southeast Asian populations had been investigated, and therefore, little was known about the purported migrations from Southeast Asia into East Asia and their roles in shaping the genetic structure of East Asian populations. Here, we present the Y-chromosome data from 1,652 individuals belonging to 47 Mon-Khmer (MK) and Hmong-Mien (HM) speaking populations that are distributed primarily across Southeast Asia and extend into East Asia. Haplogroup O3a3b-M7, which appears mainly in MK and HM, indicates a strong tie between the two groups. The short tandem repeat network of O3a3b-M7 displayed a hierarchical expansion structure (annual ring shape), with MK haplotypes being located at the original point, and the HM and the Tibeto-Burman haplotypes distributed further away from core of the network. Moreover, the East Asian dominant haplogroup O3a3c1-M117 shows a network structure similar to that of O3a3b-M7. These patterns indicate an early unidirectional diffusion from Southeast Asia into East Asia, which might have resulted from the genetic drift of East Asian ancestors carrying these two haplogroups through many small bottle-necks formed by the complicated landscape between Southeast Asia and East Asia. The ages of O3a3b-M7 and O3a3c1-M117 were estimated to be approximately 19 thousand years, followed by the emergence of the ancestors of HM lineages out of MK and the unidirectional northward migrations into East Asia.     

Phylogenetic relationship analysis of Iranians and other world populations using allele frequencies at 12 polymorphic markers

The estimation of genetic distance between populations could improve our viewpoint about human migration and its genetic origin. In this study, we used allele frequency data of 12 polymorphic markers on 250 individuals (500 alleles) from the Iranian population to estimate genetic distance between the Iranians and other world populations. The phylogenetic trees for three different sets of allele frequency data were constructed. Our results revealed the genetic similarity between the Iranians and European populations. The lowest genetic distance was observed between the Iranians and some populations reside in Russia. Furthermore, the high genetic distance was observed between the Iranians and East Asian populations. The data suggested that the Iranians might have relatively close evolutionary history with Europeans, but historically independent from East Asian populations. The evaluation of genetic distance between Indians populations and Iranians was also performed. The Indian groups showed low genetic distance with others, but high genetic distance with the Iranians. This study could provide a new insight into the evolutionary history of the Iranian population.     

Out of southern East Asia: the natural history of domestic dogs across the world

The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.     

Genetic structure of Hmong-Mien speaking populations in East Asia as revealed by mtDNA lineages

Hmong-Mien (H-M) is a major language family in East Asia, and its speakers distribute primarily in southern China and Southeast Asia. To date, genetic studies on H-M speaking populations are virtually absent in the literature. In this report, we present the results of an analysis of genetic variations in the mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS1) region and diagnostic variants in the coding regions in 537 individuals sampled from 17 H-M populations across East Asia. The analysis showed that the haplogroups that are predominant in southern East Asia, including B, R9, N9a, and M7, account for 63% (ranging from 45% to 90%) of mtDNAs in H-M populations. Furthermore, analysis of molecular variance (AMOVA), phylogenetic tree analysis, and principal component (PC) analysis demonstrate closer relatedness between H-M and other southern East Asians, suggesting a general southern origin of maternal lineages in the H-M populations. The estimated ages of the mtDNA lineages that are specific to H-M coincide with those based on archeological cultures that have been associated with H-M. Analysis of genetic distance and phylogenetic tree indicated some extent of difference between the Hmong and the Mien populations. Together with the higher frequency of north-dominating lineages observed in the Hmong people, our results indicate that the Hmong populations had experienced more contact with the northern East Asians, a finding consistent with historical evidence. Moreover, our data defined some new (sub-)haplogroups (A6, B4e, B4f, C5, F1a1, F1a1a, and R9c), which will direct further efforts to improve the phylogeny of East Asian mtDNAs.     

HLA variation reveals genetic continuity rather than population group structure in East Asia

Genetic differences between Northeast Asian (NEA) and Southeast Asian (SEA) populations have been observed in numerous studies. At the among-population level, despite a clear north–south differentiation observed for many genetic markers, debates were led between abrupt differences and a continuous pattern. At the within-population level, whether NEA or SEA populations have higher genetic diversity is also highly controversial. In this study, we analyzed a large set of HLA data from East Asia in order to map the genetic variation among and within populations in this continent and to clarify the distribution pattern of HLA lineages and alleles. We observed a genetic differentiation between NEA and SEA populations following a continuous pattern from north to south, and we show a significant and continuous decrease of HLA diversity by the same direction. This continuity is shaped by clinal distributions of many HLA lineages and alleles with increasing or decreasing frequencies along the latitude. These results bring new evidence in favor of the “overlapping model” proposed previously for East Asian peopling history, whereby modern humans migrated eastward from western Eurasia via two independent routes along each side of the Himalayas and, later, overlapped in East Asia across open land areas. Our study strongly suggests that intensive gene flow between NEA and SEA populations occurred and shaped the latitude-related continuous pattern of genetic variation and the peculiar HLA lineage and allele distributions observed in this continent. Probably for a very long period, the exact duration of these events remains to be estimated.     

Genetic Structure of Qiangic Populations Residing in the Western Sichuan Corridor

The Qiangic languages in western Sichuan (WSC) are believed to be the oldest branch of the Sino-Tibetan linguistic family, and therefore, all Sino-Tibetan populations might have originated in WSC. However, very few genetic investigations have been done on Qiangic populations and no genetic evidences for the origin of Sino-Tibetan populations have been provided. By using the informative Y chromosome and mitochondrial DNA (mtDNA) markers, we analyzed the genetic structure of Qiangic populations. Our results revealed a predominantly Northern Asian-specific component in Qiangic populations, especially in maternal lineages. The Qiangic populations are an admixture of the northward migrations of East Asian initial settlers with Y chromosome haplogroup D (D1-M15 and the later originated D3a-P47) in the late Paleolithic age, and the southward Di-Qiang people with dominant haplogroup O3a2c1*-M134 and O3a2c1a-M117 in the Neolithic Age.     

A self-developed AIM-InDel panel designed for degraded DNA analysis: Forensic application characterization and genetic landscape investigation in the Han Chinese population

To assist in forensic DNA investigation, we developed a new panel capable of simultaneously amplifying 56 ancestry-informative InDels, three Y-InDels and the Amelogenin locus in one PCR reaction. The fragment lengths of the InDel amplicons in this panel were restricted to <200 bp to benefit degraded DNA analysis. In this study, we explored the efficiency of this new panel for forensic applications in the Han Chinese population, and further shed light on the genetic structures of Han populations. We showed that the new panel could be served as an efficient tool for ancestry inference of intercontinental populations. Especially, the Han individuals in different regions could be 100% correctly predicted to be of East Asian origin with this new panel. The Han populations in different regions shared similar ancestry components in their genetic structures. Besides, we also revealed that the new panle could be useful for individual identification in different Han Chinese populations. In conclusion, we have provided the necessary evidence that the self-constructed new panel could play an important role in forensic DNA investigation.     

Diversity at eight polymorphic Alu insertion loci in Chinese populations shows evidence for European admixture in an ethnic minority population from northwest China

We have analyzed eight human-specific Alu insertion polymorphisms in four Chinese populations belonging to three ethnic groups (98 Hans from Shanghai, 80 Hans from Guangzhou, 85 Uyghurs, and 60 Sibos). All populations exhibited high levels of average heterozygosity, and those in Uyghur and Sibo were higher than predicted by the island model of population structure. The degree of genetic differentiation among these populations is statistically significant, and lower than those observed in most parts of the world except for Europe and Sahul (Australia and New Guinea). Phylogenetic analysis of these data with published data from 29 worldwide populations shows that there is a close genetic affinity among all the East Asian populations except for the Uyghur, and that the Uyghur population was found to lie between the East Asian and the West Asian populations on the population tree. The greater heterozygosity and the significant genotype associations between unlinked loci observed for the Uyghurs support the scenario that the Uyghurs might have originated from an admixture between Europeans and East Asians. This study also provides further support for the "out-of-Africa" hypothesis of modern human evolution in East Asia.     

Where west meets east: the complex mtDNA landscape of the southwest and Central Asian corridor

The southwestern and Central Asian corridor has played a pivotal role in the history of humankind, witnessing numerous waves of migration of different peoples at different times. To evaluate the effects of these population movements on the current genetic landscape of the Iranian plateau, the Indus Valley, and Central Asia, we have analyzed 910 mitochondrial DNAs (mtDNAs) from 23 populations of the region. This study has allowed a refinement of the phylogenetic relationships of some lineages and the identification of new haplogroups in the southwestern and Central Asian mtDNA tree. Both lineage geographical distribution and spatial analysis of molecular variance showed that populations located west of the Indus Valley mainly harbor mtDNAs of western Eurasian origin, whereas those inhabiting the Indo-Gangetic region and Central Asia present substantial proportions of lineages that can be allocated to three different genetic components of western Eurasian, eastern Eurasian, and south Asian origin. In addition to the overall composite picture of lineage clusters of different origin, we observed a number of deep-rooting lineages, whose relative clustering and coalescent ages suggest an autochthonous origin in the southwestern Asian corridor during the Pleistocene. The comparison with Y-chromosome data revealed a highly complex genetic and demographic history of the region, which includes sexually asymmetrical mating patterns, founder effects, and female-specific traces of the East African slave trade.