Genomic insights into the formation of human populations in East Asia.

The deep population history of East Asia remains poorly understood owing to a lack of ancient DNA data and sparse sampling of present-day people1,2. Here we report genome-wide data from 166 East Asian individuals dating to between 6000 BC and AD 1000 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 that probably reflects a coastal migration during the Late Pleistocene epoch. We also follow expansions during the subsequent Holocene epoch from four regions. First, hunter-gatherers from Mongolia and the Amur River Basin have ancestry shared by individuals who speak Mongolic and Tungusic languages, but do not carry ancestry characteristic of farmers from the West Liao River region (around 3000 BC), which contradicts theories that the expansion of these farmers spread the Mongolic and Tungusic proto-languages. Second, farmers from the Yellow River Basin (around 3000 BC) probably spread Sino-Tibetan languages, as their ancestry dispersed both to Tibet-where it forms approximately 84% of the gene pool in some groups-and to the Central Plain, where it has contributed around 59-84% to modern Han Chinese groups. Third, people from Taiwan from around 1300 BC to AD 800 derived approximately 75% of their ancestry from a lineage that is widespread in modern individuals who speak Austronesian, Tai-Kadai and Austroasiatic languages, and that we hypothesize derives from farmers of the Yangtze River Valley. Ancient people from Taiwan also derived about 25% of their ancestry from a northern lineage that is related to, but different from, farmers of the Yellow River Basin, which suggests an additional north-to-south expansion. Fourth, ancestry from Yamnaya Steppe pastoralists arrived in western Mongolia after around 3000 BC but was displaced by previously established lineages even while it persisted in western China, as would be expected if this ancestry was associated with the spread of proto-Tocharian Indo-European languages. Two later gene flows affected western Mongolia: migrants after around 2000 BC with Yamnaya and European farmer ancestry, and episodic influences of later groups with ancestry from Turan.

Improved Prediction Model of Protein Lysine Crotonylation Sites Using Bidirectional Recurrent Neural Networks.

Histone lysine crotonylation (Kcr) is a post-translational modification of histone proteins that is involved in the regulation of gene transcription, acute and chronic kidney injury, spermatogenesis, depression, cancer, and so forth. The identification of Kcr sites in proteins is important for characterizing and regulating primary biological mechanisms. The use of computational approaches such as machine learning and deep learning algorithms have emerged in recent years as the traditional wet-lab experiments are time-consuming and costly. We propose as part of this study a deep learning model based on a recurrent neural network (RNN) termed as Sohoko-Kcr for the prediction of Kcr sites. Through the embedded encoding of the peptide sequences, we investigate the efficiency of RNN-based models such as long short-term memory (LSTM), bidirectional LSTM (BiLSTM), and bidirectional gated recurrent unit (BiGRU) networks using cross-validation and independent tests. We also established the comparison between Sohoko-Kcr and other published tools to verify the efficiency of our model based on 3-fold, 5-fold, and 10-fold cross-validations using independent set tests. The results then show that the BiGRU model has consistently displayed outstanding performance and computational efficiency. Based on the proposed model, a webserver called Sohoko-Kcr was deployed for free use and is accessible at https://sohoko-research-9uu23.ondigitalocean.app.

Investigation into the origins of an ancient BRCA1 founder mutation identified among Chinese families in Singapore.

Identification of ancestry-specific pathogenic variants is imperative for diagnostic, treatment, management and prevention strategies, and to understand penetrance/modifiers on risk. Our study aimed to determine the clinical significance of a recurrent BRCA1 c.442-22_442-13del variant of unknown significance identified among 13 carriers from six Chinese families, all with a significant history of breast and/or ovarian cancer. We further aimed to establish whether this was due to a founder effect and explore its origins. Haplotype analysis, using nine microsatellite markers encompassing 2.5 megabase pairs around the BRCA1 locus, identified a common haploblock specific to the variant carriers, confirming a founder effect. Variant age was estimated to date back 77.9 generations to 69 bc using the Gamma approach. On principal component analysis using single nucleotide polymorphisms merged with 1000 Genomes dataset, variant carriers were observed to overlap predominantly with the southern Han Chinese population. To determine pathogenicity of the variant, we assessed the functional effect on RAD51 foci formation as well as replication fork stability upon induction of DNA damage and observed an impaired DNA repair response associated with the variant. In summary, we identified an ancient Chinese founder mutation dating back 77.9 generations, possibly common among individuals of southern Han Chinese descent. Using evidence from phenotypic/family history studies, segregation analysis and functional characterization, the BRCA1 variant was reclassified from uncertain significance to pathogenic.

New insights into the fine-scale history of western-eastern admixture of the northwestern Chinese population in the Hexi Corridor via genome-wide genetic legacy.

Trans-Eurasian cultural and genetic exchanges have significantly influenced the demographic dynamics of Eurasian populations. The Hexi Corridor, located along the southeastern edge of the Eurasian steppe, served as an important passage of the ancient Silk Road in Northwest China and intensified the transcontinental exchange and interaction between populations on the Central Plain and in Western Eurasia. Historical and archeological records indicate that the Western Eurasian cultural elements were largely brought into North China via this geographical corridor, but there is debate on the extent to which the spread of barley/wheat agriculture into North China and subsequent Bronze Age cultural and technological mixture/shifts were achieved by the movement of people or dissemination of ideas. Here, we presented higher-resolution genome-wide autosomal and uniparental Y/mtDNA SNP or STR data for 599 northwestern Han Chinese individuals and conducted 2 different comprehensive genetic studies among Neolithic-to-present-day Eurasians. Genetic studies based on lower-resolution STR markers via PCA, STRUCTURE, and phylogenetic trees showed that northwestern Han Chinese individuals had increased genetic homogeneity relative to northern Mongolic/Turkic/Tungusic speakers and Tibeto-Burman groups. The genomic signature constructed based on modern/ancient DNA further illustrated that the primary ancestry of the northwestern Han was derived from northern millet farmer ancestors, which was consistent with the hypothesis of Han origin in North China and more recent northwestward population expansion. This was subsequently confirmed via excess shared derived alleles in f3/f4 statistical analyses and by more northern East Asian-related ancestry in the qpAdm/qpGraph models. Interestingly, we identified one western Eurasian admixture signature that was present in northwestern Han but absent from southern Han, with an admixture time dated to approximately 1000 CE (Tang and Song dynasties). Generally, we provided supporting evidence that historic Trans-Eurasian communication was primarily maintained through population movement, not simply cultural diffusion. The observed population dynamics in northwestern Han Chinese not only support the North China origin hypothesis but also reflect the multiple sources of the genetic diversity observed in this population.

ET-GRU: using multi-layer gated recurrent units to identify electron transport proteins.

BACKGROUND: Electron transport chain is a series of protein complexes embedded in the process of cellular respiration, which is an important process to transfer electrons and other macromolecules throughout the cell. It is also the major process to extract energy via redox reactions in the case of oxidation of sugars. Many studies have determined that the electron transport protein has been implicated in a variety of human diseases, i.e. diabetes, Parkinson, Alzheimer's disease and so on. Few bioinformatics studies have been conducted to identify the electron transport proteins with high accuracy, however, their performance results require a lot of improvements. Here, we present a novel deep neural network architecture to address this problem. RESULTS: Most of the previous studies could not use the original position specific scoring matrix (PSSM) profiles to feed into neural networks, leading to a lack of information and the neural networks consequently could not achieve the best results. In this paper, we present a novel approach by using deep gated recurrent units (GRU) on full PSSMs to resolve this problem. Our approach can precisely predict the electron transporters with the cross-validation and independent test accuracy of 93.5 and 92.3%, respectively. Our approach demonstrates superior performance to all of the state-of-the-art predictors on electron transport proteins. CONCLUSIONS: Through the proposed study, we provide ET-GRU, a web server for discriminating electron transport proteins in particular and other protein functions in general. Also, our achievement could promote the use of GRU in computational biology, especially in protein function prediction.

Prioritization of SNPs in y+LAT-1 culpable of Lysinuric protein intolerance and their mutational impacts using protein-protein docking and molecular dynamics simulation studies.

Lysinuric protein intolerance (LPI) is a rare, yet inimical, genetic disorder characterized by the paucity of essential dibasic amino acids in the cells. Amino acid transporter y+LAT-1 interacts with 4F2 cell-surface antigen heavy chain to transport the required dibasic amino acids. Mutation in y+LAT-1 is rumored to cause LPI. However, the underlying pathological mechanism is unknown, and, in this analysis, we investigate the impact of point mutation in y+LAT-1's interaction with 4F2 cell-surface antigen heavy chain in causing LPI. Using an efficient and extensive computational pipeline, we have isolated M50K and L334R single-nucleotide polymorphisms to be the most deleterious mutations in y+LAT-1s. Docking of mutant y+LAT-1 with 4F2 cell-surface antigen heavy chain showed decreased interaction compared with native y+LAT-1. Further, molecular dynamic simulation analysis reveals that the protein molecules increase in size, become more flexible, and alter their secondary structure upon mutation. We believe that these conformational changes because of mutation could be the reason for decreased interaction with 4F2 cell-surface antigen heavy chain causing LPI. Our analysis gives pathological insights about LPI and helps researchers to better understand the disease mechanism and develop an effective treatment strategy.

iMotor-CNN: Identifying molecular functions of cytoskeleton motor proteins using 2D convolutional neural network via Chou's 5-step rule.

Motor proteins are the driving force behind muscle contraction and are responsible for the active transportation of most proteins and vesicles in the cytoplasm. There are three superfamilies of cytoskeletal motor proteins with various molecular functions and structures: dynein, kinesin, and myosin. The functional loss of a specific motor protein molecular function has linked to a variety of human diseases, e.g., Charcot-Marie-Tooth disease, kidney disease. Therefore, creating a precise model to classify motor proteins is essential for helping biologists understand their molecular functions and design drug targets according to their impact on human diseases. Here we attempt to classify cytoskeleton motor proteins using deep learning, which has been increasingly and widely used to address numerous problems in a variety of fields resulting in state-of-the-art results. Our effective deep convolutional neural network is able to achieve an independent test accuracy of 97.5%, 96.4%, and 96.1% for each superfamily, respectively. Compared to other state-of-the-art methods, our approach showed a significant improvement in performance across a range of evaluation metrics. Through the proposed study, we provide an effective model for classifying motor proteins and a basis for further research that can enhance the performance of protein function classification using deep learning.

iEnhancer-5Step: Identifying enhancers using hidden information of DNA sequences via Chou's 5-step rule and word embedding.

An enhancer is a short (50-1500bp) region of DNA that plays an important role in gene expression and the production of RNA and proteins. Genetic variation in enhancers has been linked to many human diseases, such as cancer, disorder or inflammatory bowel disease. Due to the importance of enhancers in genomics, the classification of enhancers has become a popular area of research in computational biology. Despite the few computational tools employed to address this problem, their resulting performance still requires improvements. In this study, we treat enhancers by the word embeddings, including sub-word information of its biological words, which then serve as features to be fed into a support vector machine algorithm to classify them. We present iEnhancer-5Step, a web server containing two-layer classifiers to identify enhancers and their strength. We are able to attain an independent test accuracy of 79% and 63.5% in the two layers, respectively. Compared to current predictors on the same dataset, our proposed method is able to yield superior performance as compared to the other methods. Moreover, this study provides a basis for further research that can enrich the field of applying natural language processing techniques in biological sequences. iEnhancer-5Step is freely accessible via http://biologydeep.com/fastenc/.

In silico screening of sugar alcohol compounds to inhibit viral matrix protein VP40 of Ebola virus.

Ebola virus is a virulent pathogen that causes highly lethal hemorrhagic fever in human and non-human species. The rapid growth of this virus infection has made the scenario increasingly complicated to control the disease. Receptor viral matrix protein (VP40) is highly responsible for the replication and budding of progeny virus. The binding of RNA to VP40 could be the crucial factor for the successful lifecycle of the Ebola virus. In this study, we aimed to identify the potential drug that could inhibit VP40. Sugar alcohols were enrich with antiviral properties used to inhibit VP40. Virtual screening analysis was perform for the 48 sugar alcohol compounds, of which the following three compounds show the best binding affinity: Sorbitol, Mannitol and Galactitol. To understand the perfect binding orientation and the strength of non-bonded interactions, individual molecular docking studies were perform for the best hits. Further molecular dynamics studies were conduct to analyze the efficacy between the protein-ligand complexes and it was identify that Sorbitol obtains the highest efficacy. The best-screened compounds obtained drug-like property and were less toxic, which could be use as a potential lead compound to develop anti-Ebola drugs.

Intentional cranial modification from the Houtaomuga Site in Jilin, China: Earliest evidence and longest in situ practice during the Neolithic Age.

OBJECTIVES: Intentional cranial modification (ICM) was a long-established tradition used to reshape the head. Unfortunately, motivation of the act is unclear. It has been found in recent and contemporary human populations throughout the Old and New Worlds, yet the drawback of the quest into the origin, diffusion, and meanings of ICM is the lack of early materials for scientific examination. This study reports the discovery of ICM from the Neolithic Houtaomuga Site in Northeast China and the importance in deepening our knowledge of this intriguing tradition. MATERIALS AND METHODS: Twenty-five skeletons unearthed from the Neolithic cultural Phases 1-4 in the Houtaomuga Site were visually screened for ICM features. Cranial measurements were conducted to quantify the degree of variation in the modified skulls and typical ones were computer tomography (CT) scanned to obtain a diploë structure and 3D model. RESULTS: Eleven skulls carrying signs of ICM from both sexes varying in age from juveniles to full adults were identified ranging from 12,000 BP to 5,000 BP. Three types of modification patterns were observed and most of them were of typical fronto-occipital modification pattern. In particular, there were remarkable variations in the curvature of the crania along the sagittal direction. DISCUSSION: Overall, the antiquity as well as the cultural and genetic continuity of the population in Houtaomuga Site demonstrated the earliest confirmed ICM cases from the easternmost Old World, and the longest in situ duration of ICM practice at one single Neolithic site. This circumstance largely contributes to our understanding of the origins and distribution of ICM in Eurasia and the American continent.

Divided zygoma in Holocene human populations from Northern China.

OBJECTIVES: Divided zygoma (DZ) occurs in contemporaneous human populations, with the highest incidences in people from East Asia and Southern Africa. The present study examines the prevalence and variation of this condition in the Holocene populations of Northern China for the first time. METHODS: In this study, 1145 skulls from various human populations living in Northern China from the Neolithic Age to recent dynasties (5000-300 years BP) were examined. Specifically, cranial measurements and a CT scan were conducted to quantify craniofacial morphology. RESULTS: Fifteen skulls were identified with DZ, revealing an overall prevalence of 1.3% in the collection, while it was determined to be higher in North Asian and Northeast Asian regional groups. In skulls with unilateral DZ, the superior division of the zygoma was generally slender, while the inferior division of the zygoma was more robust. In skulls with bilateral DZ, the maxillae were generally more laterally extended. Moreover, unilateral DZ skulls displayed differences in cortical bone thickness between two sides of the facial skeleton. DISCUSSION: In context, the distribution pattern within these data points toward a greater prevalence of the DZ phenotype in North and Northeast Asian regional groups, suggesting a hypothesis that the DZ trait is more frequent in populations characterized by flat and broad faces. Accordingly, further studies into the DZ condition will deepen our understanding of developments in plasticity, variation, and recent evolution of the human cranium.

Discovery of Eurytrema Eggs in Sediment from a Colonial Period Latrine in Taiwan.

In this study we take a closer look at the diseases that afflicted Japanese police officers who were stationed in a remote mountainous region of Taiwan from 1921 to 1944. Samples were taken from the latrine at the Huabanuo police outpost, and analyzed for the eggs of intestinal parasites, using microscopy and ELISA. The eggs of Eurytrema sp., (possibly E. pancreaticum), whipworm and roundworm were shown to be present. True infection with Eurytrema would indicate that the policemen ate uncooked grasshoppers and crickets infected with the parasite. However, false parasitism might also occur if the policemen ate the uncooked intestines of infected cattle, and the Eurytrema eggs passed through the human intestines. These findings provide an insight into the diet and health of the Japanese colonists in Taiwan nearly a century ago.

Differential Change in the Prevalence of the Ascaris, Trichuris and Clonorchis infection Among Past East Asian Populations.

As we learn more about parasites in ancient civilizations, data becomes available that can be used to see how infection may change over time. The aim of this study is to assess how common certain intestinal parasites were in China and Korea in the past 2000 years, and make comparisons with prevalence data from the 20th century. This allows us to go on to investigate how and why changes in parasite prevalence may have occurred at different times. Here we show that Chinese liver fluke (Clonorchis sinensis) dropped markedly in prevalence in both Korea and China earlier than did roundworm (Ascaris lumbricoides) and whipworm (Trichuris trichiura). We use historical evidence to determine why this was the case, exploring the role of developing sanitation infrastructure, changing use of human feces as crop fertilizer, development of chemical fertilizers, snail control programs, changing dietary preferences, and governmental public health campaigns during the 20th century.

The genetic assimilation in language borrowing inferred from Jing People.

OBJECTIVES: The Jing people are a recognized ethnic group in Guangxi, southwest China, who are the immigrants from Vietnam during the 16th century. They speak Vietnamese but with lots of language borrowings from Cantonese, Zhuang, and Mandarin. However, it's unclear if there is large-scale gene flow from surrounding populations into Jing people during their language change due to the very limited genetic information of this population. MATERIALS AND METHODS: We collected blood samples from 37 Jing and 3 Han Chinese individuals from Wanwei, Shanxin, and Wutou islands in Guangxi and genotyped about 600,000 genome-wide single nucleotide polymorphisms (SNPs). We used Principal Component Analysis (PCA), ADMIXTURE analysis, f statistics, qpWave and qpAdm to infer the population genetic structure and admixture. RESULTS: Our data revealed that the Jing people are genetically similar to the populations in southwest China and mainland Southeast Asia. But compared with Vietnamese, they show significant evidence of gene flow from surrounding East Asians. The admixture proportion is estimated to be around 35-42% in different Jing groups using southern Han Chinese as a proxy. The majority of the paternal lineages of Jing people are most likely from surrounding East Asians. DISCUSSION: We conclude that the formation and language change of present-day Jing people have involved genetic assimilation of surrounding East Asian populations. The language borrowing, in this case, is not only a cultural phenomenon but has involved demic diffusion.

The genetic admixture in Tibetan-Yi Corridor.

OBJECTIVES: The Tibetan-Yi Corridor located on the eastern edge of Tibetan Plateau is suggested to be the key region for the origin and diversification of Tibeto-Burman speaking populations and the main route of the peopling of the Plateau. However, the genetic history of the populations in the Corridor is far from clear due to limited sampling in the northern part of the Corridor. MATERIALS AND METHODS: We collected blood samples from 10 Tibetan and 10 Han Chinese individuals from Gansu province and genotyped about 600,000 genome-wide single nucleotide polymorphisms (SNPs). RESULTS: Our data revealed that the populations in the Corridor are all admixed on a genetic cline of deriving ancestry from Tibetans on the Plateau and surrounding lowland East Asians. The Tibetan and Han Chinese groups in the north of the Plateau show significant evidence of low-level West Eurasian admixture that could be probably traced back to 600∼900 years ago. DISCUSSION: We conclude that there have been huge population migrations from surrounding lowland onto the Tibetan Plateau via the Tibetan-Yi Corridor since the initial formation of Tibetans probably in Neolithic Time, which leads to the current genetic structure of Tibeto-Burman speaking populations.

Ancient Human Parasites in Ethnic Chinese Populations.

Whilst archaeological evidence for many aspects of life in ancient China is well studied, there has been much less interest in ancient infectious diseases, such as intestinal parasites in past Chinese populations. Here, we bring together evidence from mummies, ancient latrines, and pelvic soil from burials, dating from the Neolithic Period to the Qing Dynasty, in order to better understand the health of the past inhabitants of China and the diseases endemic in the region. Seven species of intestinal parasite have been identified, namely roundworm, whipworm, Chinese liver fluke, oriental schistosome, pinworm, Taenia sp. tapeworm, and the intestinal fluke Fasciolopsis buski. It was found that in the past, roundworm, whipworm, and Chinese liver fluke appear to have been much more common than the other species. While roundworm and whipworm remained common into the late 20th century, Chinese liver fluke seems to have undergone a marked decline in its prevalence over time. The iconic transport route known as the Silk Road has been shown to have acted as a vector for the transmission of ancient diseases, highlighted by the discovery of Chinese liver fluke in a 2,000 year-old relay station in northwest China, 1,500 km outside its endemic range.

A case of septic arthritis of the hip in Central Plains, China, during the Western Han Dynasty (3rd century BCE-1st century CE).

OBJECTIVE: Septic arthritis is not commonly reported in paleopathology. This study aims to provide a differential diagnosis of septic arthritis by looking at a case from ancient China. We also aim to add to the current literature on septic arthritis in paleopathology. MATERIALS: One adult male skeleton recovered from the Dapuzi Cemetery, Shaanxi, dating to the Western Han Dynasty (3rd century BCE-1st century CE). METHODS: Macroscopic observations were conducted. RESULTS: The lytic appearance and massive new bone formation on the left acetabulum of M142 are compatible with septic arthritis. The hip pathology greatly influenced his stature. The two femur shafts present different degrees of robusticity. He also showed severe osteoarthritis. CONCLUSIONS: The individual suffered from septic arthritis of the hip, of unknown cause, for a long period, which greatly influenced his daily life. Complications included osteoarthritis, shortened stature, and difficulties in walking. SIGNIFICANCE: This study offers a new case of septic arthritis and provides insight into the people who guarded the royal tombs in the West Han Dynasty. LIMITATIONS: The skeleton is not well-preserved, limiting observations of bony changes to other areas of the body.

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution InDel panel and genome-wide SNPs.

Sherpa people, one of the high-altitude hypoxic adaptive populations, mainly reside in Nepal and the southern Tibet Autonomous Region. The genetic origin and detailed evolutionary profiles of Sherpas remain to be further explored and comprehensively characterized. Here we analyzed the newly-generated InDel genotype data from 628 Dingjie Sherpas by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 1612 individuals in 191 modern and ancient populations to explore and reconstruct the fine-scale genetic structure of Sherpas and their relationships with nearby modern and ancient East Asians based on the shared alleles and haplotypes. The forensic parameters of 57 autosomal InDels (A-InDels) included in our used new-generation InDel amplification system showed that this focused InDel panel is informative and polymorphic in Dingjie Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in Dingjie Sherpas. Descriptive findings from the PCA, ADMIXTURE, and TreeMix-based phylogenies suggested that studied Nepal Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Nepal Sherpas had a different evolutionary history compared with their neighbors from Nepal (Newar and Gurung) but showed genetic similarity with 2700-year-old Chokhopani and modern Tibet Tibetans. QpAdm/qpGraph-based admixture sources and models further showed that Sherpas, core Tibetans, and Chokhopani formed one clade, which could be fitted as having the main ancestry from late Neolithic Qijia millet farmers and other deep ancestries from early Asians. Chromosome painting profiles and shared IBD fragments inferred from fineSTRUCTURE and ChromoPainter not only confirmed the abovementioned genomic affinity patterns but also revealed the fine-scale genetic microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL and iHH12 showed natural selection signatures associated with disease susceptibility in Sherpas. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the InDel-based genotype data and high-density genome-wide SNP data. The more detailed genetic landscape of Sherpa people should be further confirmed and characterized via ancient genomes or single-molecule real-time sequencing technology.

Massively parallel sequencing of 165 ancestry-informative SNPs and forensic biogeographical ancestry inference in three southern Chinese Sinitic/Tai-Kadai populations.

Ancestry informative markers (AIMs), which are distributed throughout the human genome, harbor significant allele frequency differences among diverse ethnic groups. The use of sets of AIMs to reconstruct population history and genetic relationships is attracting interest in the forensic community, because biogeographic ancestry information for a casework sample can potentially be predicted and used to guide the investigative process. However, subpopulation ancestry inference within East Asia remains in its infancy due to a lack of population reference data collection and incomplete validation work on newly developed or commercial AIM sets. In the present study, 316 Chinese persons, including 85 Sinitic-speaking Haikou Han, 120 Qiongzhong Hlai and 111 Daozhen Gelao individuals belonging to Tai-Kadai-speaking populations, were analyzed using the Precision ID Ancestry Panel (165 AISNPs). Combined with our previous 165-AISNP data (375 individuals from 6 populations), the 1000 Genomes Project and forensic literature, comprehensive population genetic comparisons and ancestry inference were further performed via ADMIXTURE, TreeMix, PCA, f-statistics and N-J tree. Although several nonpolymorphic loci were identified in the three southern Chinese populations, the forensic parameters of this ancestry inference panel were better than those for the 23 STR-based Huaxia Platinum System, which is suitable for use as a robust tool in forensic individual identification and parentage testing. The results based on the ancestry assignment and admixture proportion evaluation revealed that this panel could be used successfully to assign individuals at a continental scale but also possessed obvious limitations in discriminatory power in intercontinental individuals, especially for European-Asian admixed Uyghurs or in populations lacking reference databases. Population genetic analyses further revealed five continental population clusters and three East Asian-focused population subgroups, which is consistent with linguistic affiliations. Ancestry composition and multiple phylogenetic analysis further demonstrated that the geographically isolated Qiongzhong Hlai harbored a close phylogenetic relationship with Austronesian speakers and possessed a homogenous Tai-Kadai-dominant ancestry, which could be used as the ancestral source proxy in population history reconstruction of Tai-Kadai-speaking populations and as one of the representatives for forensic database establishment. In summary, more population-specific AIM sets focused on East Asian subpopulations, comprehensive algorithms and high-coverage population reference data should be developed and validated in the next step.

Peopling History of the Tibetan Plateau and Multiple Waves of Admixture of Tibetans Inferred From Both Ancient and Modern Genome-Wide Data.

Archeologically attested human occupation on the Tibetan Plateau (TP) can be traced back to 160 thousand years ago (kya) via the archaic Xiahe people and 30∼40 kya via the Nwya Devu anatomically modern human. However, the history of the Tibetan populations and their migration inferred from the ancient and modern DNA remains unclear. Here, we performed the first ancient and modern genomic meta-analysis among 3,017 Paleolithic to present-day Eastern Eurasian genomes (2,444 modern individuals from 183 populations and 573 ancient individuals). We identified a close genetic connection between the ancient-modern highland Tibetans and lowland island/coastal Neolithic Northern East Asians (NEA). This observed genetic affinity reflected the primary ancestry of high-altitude Tibeto-Burman speakers originated from the Neolithic farming populations in the Yellow River Basin. The identified pattern was consistent with the proposed common north-China origin hypothesis of the Sino-Tibetan languages and dispersal patterns of the northern millet farmers. We also observed the genetic differentiation between the highlanders and lowland NEAs. The former harbored more deeply diverged Hoabinhian/Onge-related ancestry and the latter possessed more Neolithic southern East Asian (SEA) or Siberian-related ancestry. Our reconstructed qpAdm and qpGraph models suggested the co-existence of Paleolithic and Neolithic ancestries in the Neolithic to modern East Asian highlanders. Additionally, we found that Tibetans from Ü-Tsang/Ando/Kham regions showed a strong population stratification consistent with their cultural background and geographic terrain. Ü-Tsang Tibetans possessed a stronger Chokhopani-affinity, Ando Tibetans had more Western Eurasian related ancestry and Kham Tibetans harbored greater Neolithic southern EA ancestry. Generally, ancient and modern genomes documented multiple waves of human migrations in the TP's past. The first layer of local hunter-gatherers mixed with incoming millet farmers and arose the Chokhopani-associated Proto-Tibetan-Burman highlanders, which further respectively mixed with additional genetic contributors from the western Eurasian Steppe, Yellow River and Yangtze River and finally gave rise to the modern Ando, Ü-Tsang and Kham Tibetans.