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Fulltext Was Wuhan the early epicenter of the COVID-19 pandemic?-A critique

Cao Y, Chen L, Chen H, Cun Y, Dai X, Du H, et al.

Natl Sci Rev, 2023 Apr;10(4):nwac287.
PMID: 37089192 DOI: 10.1093/nsr/nwac287
Fulltext View of Pakistani Residents toward Coronavirus Disease (COVID-19) during a Rapid Outbreak: A Rapid Online Survey

Hayat K, Rosenthal M, Xu S, Arshed M, Li P, Zhai P, et al.

Int J Environ Res Public Health, 2020 05 12;17(10).
PMID: 32408528 DOI: 10.3390/ijerph17103347

BACKGROUND: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public's perspective about COVID-19, including their knowledge, attitude, and practices.
METHODS: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann-Whitney tests, Kruskal-Wallis tests, and regression analysis were carried out during data analysis.
RESULTS: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants.
CONCLUSION: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education.
Fulltext The temporal trend of disease burden attributable to metabolic risk factors in China, 1990-2019: An analysis of the Global Burden of Disease study

Jin Y, So H, Cerin E, Barnett A, Mubarik S, Hezam K, et al.

Front Nutr, 2022;9:1035439.
PMID: 36687675 DOI: 10.3389/fnut.2022.1035439

BACKGROUND AND AIMS: The disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries.
METHODS: The main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression.
RESULTS: For all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20-49 and at age 70-95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors.
CONCLUSIONS: Population aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively.
The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia

Deng L, Hoh BP, Lu D, Fu R, Phipps ME, Li S, et al.

Hum Genet, 2014 Sep;133(9):1169-85.
PMID: 24916469 DOI: 10.1007/s00439-014-1459-8

Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration history in Southeast Asia.
Fulltext The Peopling and Migration History of the Natives in Peninsular Malaysia and Borneo: A Glimpse on the Studies Over the Past 100 years

Hoh BP, Deng L, Xu S

Front Genet, 2022;13:767018.
PMID: 35154269 DOI: 10.3389/fgene.2022.767018

Southeast Asia (SEA) has one of the longest records of modern human habitation out-of-Africa. Located at the crossroad of the mainland and islands of SEA, Peninsular Malaysia is an important piece of puzzle to the map of peopling and migration history in Asia, a question that is of interest to many anthropologists, archeologists, and population geneticists. This review aims to revisit our understanding to the population genetics of the natives from Peninsular Malaysia and Borneo over the past century based on the chronology of the technology advancement: 1) Anthropological and Physical Characterization; 2) Blood Group Markers; 3) Protein Markers; 4) Mitochondrial and Autosomal DNA Markers; and 5) Whole Genome Analysis. Subsequently some missing gaps of the study are identified. In the later part of this review, challenges of studying the population genetics of natives will be elaborated. Finally, we conclude our review by reiterating the importance of unveiling migration history and genetic diversity of the indigenous populations as a steppingstone towards comprehending disease evolution and etiology.
The Effects of Bacillus subtilis QST713 and β-mannanase on growth performance, intestinal barrier function, and the gut microbiota in weaned piglets

Liu J, Ma X, Zhuo Y, Xu S, Hua L, Li J, et al.

J Anim Sci, 2023 Jan 03;101.
PMID: 37583344 DOI: 10.1093/jas/skad257

We investigated the effects of different Bacillus subtilis QST713 doses and a B. subtilis QST713 and β-mannanase mix on growth performance, intestinal barrier function, and gut microbiota in weaned piglets. In total, 320 healthy piglets were randomly assigned to four groups: 1) control group (basal diet), 2) BS100 group (basal diet plus 100 mg/kg B. subtilis QST713), 3) BS200 group (basal diet plus 200 mg/kg B. subtilis QST713), and 4) a BS100XT group (basal diet plus 100 mg/kg B. subtilis QST713 and 150 mg/kg β-mannanase). The study duration was 42 d. We showed that feed intake in weaned piglets on days 1 to 21 was increased in group BS100 (P < 0.05), and that the feed conversion ratio in group BS100XT animals decreased throughout the study (P < 0.05). In terms of microbial counts, the BS100XT group showed reduced Escherichia coli and Clostridium perfringens numbers on day 21 (P < 0.05). Moreover, no significant α-diversity differences were observed across all groups during the study (P > 0.05). However, principal coordinates analysis indicated clear separations in bacterial community structures across groups (analysis of similarities: P < 0.05) on days 21 and 42. Additionally, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression in piglet feces increased (P < 0.05) by adding B. subtilis QST713 and β-mannanase to diets. Notably, this addition decreased short-chain fatty acid concentrations. In conclusion, B. subtilis QST713 addition or combined B. subtilis QST713 plus β-mannanase effectively improved growth performance, intestinal barrier function, and microbial balance in weaned piglets.
Fulltext The Effect of Precursor Concentration on the Particle Size, Crystal Size, and Optical Energy Gap of CexSn1-xO2 Nanofabrication

Al-Hada NM, Md Kasmani R, Kasim H, Al-Ghaili AM, Saleh MA, Banoqitah EM, et al.

Nanomaterials (Basel), 2021 Aug 22;11(8).
PMID: 34443973 DOI: 10.3390/nano11082143

In the present work, a thermal treatment technique is applied for the synthesis of CexSn1-xO2 nanoparticles. Using this method has developed understanding of how lower and higher precursor values affect the morphology, structure, and optical properties of CexSn1-xO2 nanoparticles. CexSn1-xO2 nanoparticle synthesis involves a reaction between cerium and tin sources, namely, cerium nitrate hexahydrate and tin (II) chloride dihydrate, respectively, and the capping agent, polyvinylpyrrolidone (PVP). The findings indicate that lower x values yield smaller particle size with a higher energy band gap, while higher x values yield a larger particle size with a smaller energy band gap. Thus, products with lower x values may be suitable for antibacterial activity applications as smaller particles can diffuse through the cell wall faster, while products with higher x values may be suitable for solar cell energy applications as more electrons can be generated at larger particle sizes. The synthesized samples were profiled via a number of methods, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). As revealed by the XRD pattern analysis, the CexSn1-xO2 nanoparticles formed after calcination reflect the cubic fluorite structure and cassiterite-type tetragonal structure of CexSn1-xO2 nanoparticles. Meanwhile, using FT-IR analysis, Ce-O and Sn-O were confirmed as the primary bonds of ready CexSn1-xO2 nanoparticle samples, whilst TEM analysis highlighted that the average particle size was in the range 6-21 nm as the precursor concentration (Ce(NO3)3·6H2O) increased from 0.00 to 1.00. Moreover, the diffuse UV-visible reflectance spectra used to determine the optical band gap based on the Kubelka-Munk equation showed that an increase in x value has caused a decrease in the energy band gap and vice versa.
Fulltext Targeted DNA complementation on a 1,1'-carbonyldiimidazole-functionalized surface for identifying Mycobacterium tuberculosis

Xu S, Xue Y, Guo F, Xu M, Gopinath SCB, Mao X

3 Biotech, 2020 May;10(5):227.
PMID: 32373419 DOI: 10.1007/s13205-020-02216-2

Herein, a rapid and sensitive current-volt measurement was developed for identifying the IS6110 DNA sequence to diagnose Mycobacterium tuberculosis (TB). An aminated capture probe was immobilized on a 1,1'-carbonyldiimidazole-functionalized interdigitated electrode (IDE) silica substrate, and the target sequence was detected by complementation. It was found that all tested concentrations displayed a higher response in current changes than the control, and the limit of detection was 10 fM. The sensitivity ranged from 1 to 10 fM. The control sequences with single-, triple-mismatch and noncomplementary sequences showed great discrimination. This rapid and easy DNA detection method helps to identify M. tuberculosis for early-stage diagnosis of TB.
Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: Implications for lipoprotein binding and atherosclerosis

Afroz R, Cao Y, Rostam MA, Ta H, Xu S, Zheng W, et al.

Pharmacol Ther, 2018 07;187:88-97.
PMID: 29454855 DOI: 10.1016/j.pharmthera.2018.02.005

Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans are a class of GAGs, commonly observed on PGs. Multiple enzymes are involved in galactosaminoglycan biosynthesis. Galactosaminoglycan synthesis is regulated by various signalling pathways which are amenable to pharmacological manipulation to treat atherosclerosis. Receptor mediated signalling pathways including protein tyrosine kinase receptors (PTKRs), serine/threonine kinase receptors (S/TKRs) and G-protein coupled receptors (GPCRs) pathways regulate galactosaminoglycan synthesizing enzyme expression. Increased expression of these enzymes modify galactosaminoglycan chain structure by making them hyperelongated. This review focuses on the signalling pathways regulating the expression of genes involved in galactosaminoglycan synthesis and modification. Furthermore, there are multiple other processes for inhibiting the interactions between LDL and galactosaminoglycans such as peptide mimetics of ApoB100 and anti-galactosaminoglycan antibodies and the therapeutic potential of these strategies is also addressed.
Fulltext Shared Signature of Recent Positive Selection on the TSBP1-BTNL2-HLA-DRA Genes in Five Native Populations from North Borneo

Hoh BP, Zhang X, Deng L, Yuan K, Yew CW, Saw WY, et al.

Genome Biol Evol, 2020 12 06;12(12):2245-2257.
PMID: 33022050 DOI: 10.1093/gbe/evaa207

North Borneo (NB) is home to more than 40 native populations. These natives are believed to have undergone local adaptation in response to environmental challenges such as the mosquito-abundant tropical rainforest. We attempted to trace the footprints of natural selection from the genomic data of NB native populations using a panel of ∼2.2 million genome-wide single nucleotide polymorphisms. As a result, an ∼13-kb haplotype in the Major Histocompatibility Complex Class II region encompassing candidate genes TSBP1-BTNL2-HLA-DRA was identified to be undergoing natural selection. This putative signature of positive selection is shared among the five NB populations and is estimated to have arisen ∼5.5 thousand years (∼220 generations) ago, which coincides with the period of Austronesian expansion. Owing to the long history of endemic malaria in NB, the putative signature of positive selection is postulated to be driven by Plasmodium parasite infection. The findings of this study imply that despite high levels of genetic differentiation, the NB populations might have experienced similar local genetic adaptation resulting from stresses of the shared environment.
Preparation and characterization of bioplastics from silylated cassava starch and epoxidized soybean oils

Yang J, Xu S, Wang W, Ran X, Ching YC, Sui X, et al.

Carbohydr Polym, 2023 Jan 15;300:120253.
PMID: 36372510 DOI: 10.1016/j.carbpol.2022.120253

In this work, a systematic coupling study of silane coupling agent between starch and epoxidized soybean oils (ESO) was carried out. Starch was modified by 3-aminopropyl trimethoxy silane (APMS) with various contents of NaOH. The APMS-modified starch was incorporated with ESO to synthesize the bioplastics by solution casting. As demonstrated by the FTIR spectra, the hydrogen bond interactions among starch molecules were inhibited by the modification. This outcome provided higher interaction and compatibility of starch with ESO, as confirmed by FESEM. TGA showed that the thermal stability of starch decreased considerably after the silylation. In contrast, the produced bioplastics with silylated starch exhibited higher thermal stability than the control sample. Regarding the bioplastics, an obvious increase of tensile strength from 5.78 MPa to 9.29 MPa was obtained. This work suggested a simple and effective modification technique by APMS to improve compatibility of starch/ESO-based bioplastics with superior mechanical and thermal properties.
Fulltext Population genetic structure of peninsular Malaysia Malay sub-ethnic groups

Hatin WI, Nur-Shafawati AR, Zahri MK, Xu S, Jin L, Tan SG, et al.

PLoS One, 2011;6(4):e18312.
PMID: 21483678 DOI: 10.1371/journal.pone.0018312

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia.
Fulltext PanSNPdb: the Pan-Asian SNP genotyping database

Ngamphiw C, Assawamakin A, Xu S, Shaw PJ, Yang JO, Ghang H, et al.

PLoS One, 2011;6(6):e21451.
PMID: 21731755 DOI: 10.1371/journal.pone.0021451

The HUGO Pan-Asian SNP consortium conducted the largest survey to date of human genetic diversity among Asians by sampling 1,719 unrelated individuals among 71 populations from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, and Thailand. We have constructed a database (PanSNPdb), which contains these data and various new analyses of them. PanSNPdb is a research resource in the analysis of the population structure of Asian peoples, including linkage disequilibrium patterns, haplotype distributions, and copy number variations. Furthermore, PanSNPdb provides an interactive comparison with other SNP and CNV databases, including HapMap3, JSNP, dbSNP and DGV and thus provides a comprehensive resource of human genetic diversity. The information is accessible via a widely accepted graphical interface used in many genetic variation databases. Unrestricted access to PanSNPdb and any associated files is available at: http://www4a.biotec.or.th/PASNP.
Fulltext PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations

Zhang C, Gao Y, Ning Z, Lu Y, Zhang X, Liu J, et al.

Genome Biol, 2019 10 22;20(1):215.
PMID: 31640808 DOI: 10.1186/s13059-019-1838-5

Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of population genetics and molecular evolution, we developed a database, PGG.SNV ( https://www.pggsnv.org ), which gives much higher weight to previously under-investigated indigenous populations in Asia. PGG.SNV archives 265 million SNVs across 220,147 present-day genomes and 1018 ancient genomes, including 1009 newly sequenced genomes, representing 977 global populations. Moreover, estimation of population genetic diversity and evolutionary parameters is available in PGG.SNV, a unique feature compared with other databases.
Fulltext Multi-view secondary input collaborative deep learning for lung nodule 3D segmentation

Dong X, Xu S, Liu Y, Wang A, Saripan MI, Li L, et al.

Cancer Imaging, 2020 Aug 01;20(1):53.
PMID: 32738913 DOI: 10.1186/s40644-020-00331-0

BACKGROUND: Convolutional neural networks (CNNs) have been extensively applied to two-dimensional (2D) medical image segmentation, yielding excellent performance. However, their application to three-dimensional (3D) nodule segmentation remains a challenge.
METHODS: In this study, we propose a multi-view secondary input residual (MV-SIR) convolutional neural network model for 3D lung nodule segmentation using the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) dataset of chest computed tomography (CT) images. Lung nodule cubes are prepared from the sample CT images. Further, from the axial, coronal, and sagittal perspectives, multi-view patches are generated with randomly selected voxels in the lung nodule cubes as centers. Our model consists of six submodels, which enable learning of 3D lung nodules sliced into three views of features; each submodel extracts voxel heterogeneity and shape heterogeneity features. We convert the segmentation of 3D lung nodules into voxel classification by inputting the multi-view patches into the model and determine whether the voxel points belong to the nodule. The structure of the secondary input residual submodel comprises a residual block followed by a secondary input module. We integrate the six submodels to classify whether voxel points belong to nodules, and then reconstruct the segmentation image.
RESULTS: The results of tests conducted using our model and comparison with other existing CNN models indicate that the MV-SIR model achieves excellent results in the 3D segmentation of pulmonary nodules, with a Dice coefficient of 0.926 and an average surface distance of 0.072.
CONCLUSION: our MV-SIR model can accurately perform 3D segmentation of lung nodules with the same segmentation accuracy as the U-net model.
Fulltext Modification of the contact surfaces for improving the puncture resistance of laminar structures

Wang P, Yang J, Li X, Liu M, Zhang X, Sun D, et al.

Sci Rep, 2017 07 26;7(1):6615.
PMID: 28747656 DOI: 10.1038/s41598-017-06007-3

Uncovering energy absorption and surface effects of various penetrating velocities on laminar structures is essential for designing protective structures. In this study, both quasi-static and dynamic penetration tests were systematical conducted on the front surfaces of metal sheets coated with a graphene oxide (GO) solution and other media. The addition of a GO fluid film to the front impact surface aided in increasing the penetration strength, improving the failure extension and dissipating additional energy under a wide-range of indentation velocity, from 3.33 × 10-5 m/s to 4.42 m/s. The coated -surfaces improved the specific energy dissipation by approximately 15~40% relative to the dry-contact configuration for both single-layer and double-layer configurations, and specific energy dissipations of double-layer configurations were 20~30% higher than those of the single-layer configurations. This treatment provides a facile strategy in changing the contact state for improving the failure load and dissipate additional energy.
Influence of starch silylation on the structures and properties of starch/epoxidized soybean oil-based bioplastics

Yang J, Xu S, Chee CY, Ching KY, Wei Y, Wang R, et al.

Int J Biol Macromol, 2024 Feb;258(Pt 2):129037.
PMID: 38158061 DOI: 10.1016/j.ijbiomac.2023.129037

The present work systematically investigated the influence of starch silylation on the structures and properties of starch/epoxidized soybean oil-based bioplastics. Silylated starch was synthesized using starch particles (SP-ST) or gelatinized starch (SG-ST) under different silane hydrolysis pHs. Due to the appearance of -NH2 groups and lower OH wavenumbers, SP-ST obtained at pH 5 showed higher silylation degree and stronger hydrogen bond interaction with epoxidized soybean oils (ESO) than that at pH 11. The morphology analysis revealed better interfacial compatibility of ESO and SP-ST. The tensile strength of the samples containing SP-ST increased by 51.91 % than the control, emphasizing the enhanced interaction within the bioplastics. However, tensile strength of the bioplastics with SG-ST decreased by 59.56 % due to their high moisture contents from unreacted silanes. Additionally, the bioplastics with SG-ST exhibited an obvious reduction of thermal stability and an increase in water solubility because of the presence of unreacted APMS. The bioplastic degradation was not prevented by starch silylation except high pH. The bioplastics showed the most desirable tensile properties, thermal stability, and water solubility when starch was surface-modified with silanes hydrolyzed at pH 5. These outcomes made the fabricated bioplastics strong candidates for petroleum-based plastics for packaging applications.
Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia

Yew CW, Lu D, Deng L, Wong LP, Ong RT, Lu Y, et al.

Hum Genet, 2018 Feb;137(2):161-173.
PMID: 29383489 DOI: 10.1007/s00439-018-1869-0

Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28-37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50-33 thousand years ago (kya), followed by East Asian (~ 40-15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
Genetic relatedness of indigenous ethnic groups in northern Borneo to neighboring populations from Southeast Asia, as inferred from genome-wide SNP data

Yew CW, Hoque MZ, Pugh-Kitingan J, Minsong A, Voo CLY, Ransangan J, et al.

Ann. Hum. Genet., 2018 07;82(4):216-226.
PMID: 29521412 DOI: 10.1111/ahg.12246

The region of northern Borneo is home to the current state of Sabah, Malaysia. It is located closest to the southern Philippine islands and may have served as a viaduct for ancient human migration onto or off of Borneo Island. In this study, five indigenous ethnic groups from Sabah were subjected to genome-wide SNP genotyping. These individuals represent the "North Borneo"-speaking group of the great Austronesian family. They have traditionally resided in the inland region of Sabah. The dataset was merged with public datasets, and the genetic relatedness of these groups to neighboring populations from the islands of Southeast Asia, mainland Southeast Asia and southern China was inferred. Genetic structure analysis revealed that these groups formed a genetic cluster that was independent of the clusters of neighboring populations. Additionally, these groups exhibited near-absolute proportions of a genetic component that is also common among Austronesians from Taiwan and the Philippines. They showed no genetic admixture with Austro-Melanesian populations. Furthermore, phylogenetic analysis showed that they are closely related to non-Austro-Melansian Filipinos as well as to Taiwan natives but are distantly related to populations from mainland Southeast Asia. Relatively lower heterozygosity and higher pairwise genetic differentiation index (FST ) values than those of nearby populations indicate that these groups might have experienced genetic drift in the past, resulting in their differentiation from other Austronesians. Subsequent formal testing suggested that these populations have received no gene flow from neighboring populations. Taken together, these results imply that the indigenous ethnic groups of northern Borneo shared a common ancestor with Taiwan natives and non-Austro-Melanesian Filipinos and then isolated themselves on the inland of Sabah. This isolation presumably led to no admixture with other populations, and these individuals therefore underwent strong genetic differentiation. This report contributes to addressing the paucity of genetic data on representatives from this strategic region of ancient human migration event(s).
Fulltext Genetic Connections and Convergent Evolution of Tropical Indigenous Peoples in Asia

Deng L, Pan Y, Wang Y, Chen H, Yuan K, Chen S, et al.

Mol Biol Evol, 2022 Feb 03;39(2).
PMID: 34940850 DOI: 10.1093/molbev/msab361

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, whereas their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large interarea genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.

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