Biology subjects

He, G.

Publications and source records attributed to He, G..

At least 73 records · Page 4Linked to original sources

bioRxiv2021

Screening and selection of 21 novel microhaplotype markers for ancestry inference in ten Chinese Subpopulations

Genetic findings suggested that ethnolinguistically diverse populations in China harbor differentiated genetic structure and complex evolutionary admixture history, which provide the genetic basis and theoretical foundation for forensic biogeographical ancestry inference (BGAI). Forensic assays for BGAI among intracontinental eastern Eurasians were previously conducted mainly based on the SNPs or InDels. Microhaplotypes, as a set of closely linked SNPs within 200 base pairs, possess the advantages of both STR and SNP and have great potential in forensic ancestry inference. However, the developed forensic assay based on the ancestry informative microhaplotypes in the BGAI remained to be comprehensively explored, especially in China with enriching genetic diversity. Here, we described a new BGAI panel based on 21 novel identified ancestry informative microhaplotypes that focused on dissected finer-scale ancestry composition of Chinese populations. We initially screened all possible microhaplotypes with high Fst values among five East Asian populations and finally employed 21 candidate microhaplotypes in two multiplex SNaPshot assays. Forensic amplification efficiency and statistically/physically phased haplotypes of the 21 microhaplotypes were validated using both SNaPshot and massively parallel sequencing (MPS) platforms. Followingly, we validated the efficiency of these microhaplotypes for BGAI in 764 individuals from ten Chinese populations. Fine-scale ancestry source and ancestry proportion estimated by the principal component analysis (PCA), multidimensional scaling (MDS), phylogenetic tree and model-based STRUCTURE among worldwide populations and East Asians showed that our customized panel could provide a higher discrimination resolution in both continental population stratification and East Asian regional substructure. East Asian populations could be further classified into linguistically/geographically different intracontinental subpopulations (Tibeto-Burman, Tai-Kadai and others). Finally, we obtained a higher estimated accuracy using training and tested datasets in the microhaplotype-based panel than traditional SNP-based panels. Generally, the above results demonstrated that this microhaplotype panel was robust and suitable for forensic BGAI in Chinese populations, which not only provided a high discriminatory power for continental populations but also discriminated East Asians into linguistically restricted subpopulations.

genetics↗

bioRxiv2021

Demographic model and biological adaptation inferred from the genome-wide SNP data reveal tripartite origins of southernmost Chinese Huis

The culturally unique Sanya Hui (SYH) people are regarded as the descendants of ancient Cham people in Central Vietnam (CV) and exhibit a scenario of complex migration and admixture history, who were likely to first migrate from Central and South Asia (CSA) to CV and then to South Hainan and finally assimilated with indigenous populations and resided in the tropical island environments since then. A long-standing hypothesis posits that SYH derives from different genetic and cultural origins, which hypothesizes that SYH people are different from the genetically attested admixture history of northern Hui people possessing major Han-related ancestry and minor western Eurasian ancestry. However, the effect of the cultural admixture from CSA and East Asia (EA) on the genetic admixture of SYH people remains unclear. Here, we reported the first batch of genome-wide SNP data from 94 SYH people from Hainan and comprehensively characterized their genetic structure, origin, and admixture history. Our results found that SYH people were genetically different from the northern Chinese Hui people and harbored a close genomic affinity with indigenous Vietnamese but a distinct relationship with Cham, which confirmed the hypothesis of documented recent historical migration from CV and assimilation with Hainan indigenous people. The fitted admixture models and reconstructed demographic frameworks revealed an additional influx of CSA and EA ancestries during the historical period, consisting of the frequent cultural communication along the Southern Maritime Silk Road and extensive interaction with EA. Analyses focused on natural-selected signatures of SYH people revealed a similar pattern with mainland East Asians, which further confirmed the possibility of admixture-induced biological adaptation of island environments. Generally, three genetically attested ancestries from CV, EA, and CSA in modern SYH people supported their tripartite model of genomic origins.

genetics↗

bioRxiv2021

Genomic insights into the population history and biological adaptation of Southwestern Chinese Hmong-Mien people

Hmong-Mien-speaking (HM) populations, widely distributed in South China, North of Thailand, Laos and Vietnam, have experienced different settlement environments, dietary habits and pathogen exposure. However, their specific biological adaptation also remained largely uncharacterized, which is important in the population evolutionary genetics and Trans-Omics for regional Precision Medicine. Besides, the origin and genetic diversity of HM people and their phylogenetic relationship with surrounding modern and ancient populations are unknown. Here, we reported genome-wide SNPs in 52 representative Miao people and combined them with 144 HM people from 13 geographically representative populations to characterize the full genetic admixture and adaptive landscape of HM speakers. We found that obvious genetic substructures existed in geographically different HM populations and also identified one new ancestral lineage specifically exited in HM people, which spatially distributed from Sichuan and Guizhou in the North to Thailand in the South and temporally dated to at least 500 years. The sharing patterns of the newly-identified homogeneous ancestry component combined the estimated admixture times via the decay of Linkage Disequilibrium and haplotype sharing in GLOBETROTTER suggested that the modern HM-speaking populations originated from Southwest China and migrated southward recently, which is consistent with the reconstructed phenomena of linguistic and archeological documents. Additionally, we identified specific adaptive signatures associated with several important human nervous system biological functions. Our pilot work emphasized the importance of anthropologically-informed sampling and deeply genetic structure reconstruction via whole-genome sequencing in the next step in the deep Chinese population genomic diversity project (CPGDP), especially in the ethnolinguistic regions.

genetics↗

bioRxiv2021

WUSCHEL-Related Homeobox Genes Cooperate with Cytokinin Signalling to Promote Bulbil Formation in Lilium lancifolium

The bulbil is an important vegetative reproductive organ in triploid Lilium lancifolium. Based on our previously obtained transcriptome data, we screened two WUSCHCEL-related homeobox (WOX) genes closely related to bulbil formation, LlWOX9 and LlWOX11. However, the biological functions and regulatory mechanisms of LlWOX9 and LlWOX11 are unclear. In this study, we cloned the full-length coding sequences of LlWOX9 and LlWOX11. Transgenic Arabidopsis showed increased branch numbers, and the overexpression of LlWOX9 and LlWOX11 in stem segments promoted bulbil formation, while the silencing of LlWOX9 and LlWOX11 inhibited bulbil formation, indicating that LlWOX9 and LlWOX11 are positive regulators of bulbil formation. Cytokinins acting through type-B response regulators (type-B RRs) could bind to the promoters of LlWOX9 and LlWOX11 and promote their transcription. LlWOX11 could enhance cytokinin pathway signalling by inhibiting the transcription of type-A LlRR9. Our study enriches the understanding of the regulation of plant development by the WOX gene family and lays a foundation for further research on the molecular mechanism of bulbil formation in lily.

developmental biology↗

bioRxiv2021

The northern gene flow into southeastern East Asians inferred from genome-wide array genotyping

The population history of Southeast China remains poorly understood due to the sparse sampling of present-day populations and far less modeling with ancient genomic data. We here newly reported genome-wide genotyping data from 207 present-day Han Chinese and Hmong-Mien-speaking She people from Fujian and Taiwan, southeast China. We co-analyzed with 66 early-Neolithic to Iron-Age ancient Fujian and Taiwan individuals obtained from literature to explore the genetic continuity and admixture based on the genetic variations of high-resolution time transect. We found the genetic differentiation between northern and southern East Asians defined by a north-south East Asian genetic cline and the studied southern East Asians were clustered in the southern end of this cline. We also found that southeastern coastal continental modern East Asians harbored the genetic differentiation with other southern Tai-Kadai, Hmong-Mien, Austronesian and Austroasiatic speakers, as well as geographically close Neolithic-to-Iron Age populations, but relatedly close to post-Neolithic Yellow River ancients, which suggested the influence of southward gene flow on the modern southern coastal gene pool. Besides, we also identified one new Hmong-Mien genetic cline in East Asia with the coastal Fujian She localizing at the intersection position between Hmong-Mien and Han clines in the principal component analysis. She people show stronger genetic affinity with southern East Asian indigenous populations with the main ancestry deriving from Hanben-related populations. The southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to southeastern ancient indigenous rice farmers, which was consistent with the northern China origin of modern southeastern Han Chinese and in line with the historically and archaeologically attested southward migrations of Han people and their ancestors. Interestingly, f4-statistics and three-way admixture model results showed both coastal ancient sources related to Austronesian speakers and inland ancient sources related to Austroasiatic speakers complexed the modern observed fine-scale genetic structure here. Our estimated north-south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze age to historic periods, suggesting the recent large-scale population migrations and subsequent admixture participated in the formation of modern Han in Southeast Asia.

genetics↗

bioRxiv2021

Genomic insights into the differentiated population admixture structure and demographic history of North East Asians

North China and South Siberia, mainly populated by Altaic-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroad for the initial peopling of America and western-eastern trans-continental communication. Yet, the complex scenarios of genetic origin, population structure, and admixture history of North-East Asia remain to be fully characterized, especially for Mongolic people in China with a genome-wide perspective. Thus, we genotyped genome-wide SNPs for 510 individuals from 38 Chinese Mongolic, Tungusic, and Sinitic populations to explore the sharing alleles and haplotypes within the studied groups and following merged it with 3508 modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified significant substructures within Altaic-speaking populations with the primary common ancestry linked to the Neolithic northern East Asians: Western Turkic people harbored more western Eurasian ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed dominant Neolithic Mongolian Plateau (MP) or ARB ancestry; Southern Mongolic people in China owned obvious genetic impact from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians and the latter retained the dominant YRB and ARB Neolithic ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountain possessed a strong genetic affinity with Neolithic MP people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historic pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to southern ones. We finally found natural signatures in Mongolians associated with alcohol metabolism. Generally, our results not only illuminated that complex population migration and admixture of Neolithic ancestral sources from the MP or ARB played an important role in the spread of Altaic-speaking populations and Proto-Altaic language, which partly supported the Northeast Asia-origin hypothesis, but also demonstrated that the observed multi-sources of genetic diversity contributed significantly to the modern existing extensive ethnolinguistic diversity in North-East Asia.

genomics↗

bioRxiv2021

Co-cultivation of the anaerobic fungus Caecomyces churrovis with Methanobacterium bryantii enhances transcription of carbohydrate binding modules

Anaerobic fungi and methanogenic archaea are two classes of microorganisms found in the rumen microbiome that metabolically interact during lignocellulose breakdown. Here, stable synthetic co-cultures of the anaerobic fungus Caecomyces churrovis and the methanogen Methanobacterium bryantii (not native to the rumen) were formed, demonstrating that microbes from different environments can be paired based on metabolic ties. Transcriptional and metabolic changes induced by methanogen co-culture were evaluated in C. churrovis across a variety of substrates to identify mechanisms that impact biomass breakdown and sugar uptake. A high-quality genome of C. churrovis was obtained and annotated, which is the first sequenced genome of a non-rhizoid forming anaerobic fungus. C. churrovis possess an abundance of CAZymes and carbohydrate binding modules and, in agreement with previous studies of early-diverging fungal lineages, N6-methyldeoxyadenine (6mA) was associated with transcriptionally active genes. Co-culture with the methanogen increased overall transcription of CAZymes, carbohydrate binding modules, and dockerin domains in co-cultures grown on both lignocellulose and cellulose and caused upregulation of genes coding associated enzymatic machinery including carbohydrate binding modules in family 18 and dockerin domains across multiple growth substrates relative to C. churrovis monoculture. Two other fungal strains grown on a reed canary grass substrate in co-culture with the same methanogen also exhibited high log2fold change values for upregulation of genes encoding carbohydrate binding modules in families 1 and 18. Transcriptional upregulation indicated that co-culture of the C. churrovis strain with a methanogen may enhance pyruvate formate lyase (PFL) function for growth on xylan and fructose and production of bottleneck enzymes in sugar utilization pathways, further supporting the hypothesis that co-culture with a methanogen may enhance certain fungal metabolic functions. Upregulation of CBM18 may play a role in fungal-methanogen physical associations and fungal cell wall development and remodeling.

microbiology↗

bioRxiv2021

A natural marmoset model of genetic generalized epilepsy.

As a common neurological disease, epilepsy has been extensively studied. Efforts have been made on rodent and other animal models to reveal the pathogenic mechanisms of epilepsy and develop new drugs as treatment. However, the features of current epilepsy models cannot fully mimic different kinds of epilepsy in human, asking for non-human primates models of epilepsy. The common marmoset (Callithrix jacchus) is a New World monkey that is widely used to study brain function. Here, we show a natural marmoset model of generalized epilepsy. In this unique marmoset family, generalized epilepsy was successfully induced by handling operation in some individuals. We mapped the marmoset family with handling-sensitive epilepsy and found that epileptic marmoset had an autosomal dominant genetic predisposition. Those marmosets were more sensitive to epilepsy inducers pentylenetetrazol (PTZ). By electrocorticogram (ECoG) recording, we detected epileptic discharge in marmoset with history of seizures. However, there was no significant change in the overall structure of epileptic marmoset brain. In summary, we report a family of marmosets with generalized seizures induced by handling operation. This epileptic marmoset family provides insights to better understand the mechanism of generalized epilepsy and helps to develop new therapeutic methods. Short summaryDespite the rodent and other animal models on epilepsy, a common neurological disease, the understanding of the pathogenic mechanisms of epilepsy and treatment are yet to be advanced., Non-human primates are good experimental animals for modelling neurological disease. Here we report a common marmoset family with generalized epilepsy induced by handling stimulation. We mapped the epileptic marmoset family and found that epilepsy had a genetic predisposition. The present report deals in detail with the phenotypes and characteristics of epileptic marmosets. This natural marmoset reflect epilepsy model will help to better understand the mechanism of epilepsy and develop new therapeutic methods.

neuroscience↗

bioRxiv2021

Genomic history and forensic characteristics of Sherpa highlanders on the Tibetan Plateau inferred from high-resolution genome-wide InDels and 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 Sherpa people by merging with 4222 worldwide InDel profiles and collected genome-wide SNP data (approximately 600K SNPs) from 3324 individuals in 382 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 updated InDel panel is informative and polymorphic in Sherpas, suggesting that it can be used as the supplementary tool for forensic personal identification and parentage testing in the highland East Asians. Descriptive findings from the PCA, ADMIXTURE and TreeMix-based phylogeny suggested that Sherpas showed excess allele sharing with neighboring Tibeto-Burman Tibetans. Furthermore, patterns of allele sharing in f-statistics demonstrated that Sherpa people 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 Sherpa, 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 microstructures among Sino-Tibetan speakers. Finally, natural-selection signals revealed via iHS, nSL, and iHH12 showed signatures associated with disease susceptibility in Sherpa people. Generally, we provided the comprehensive landscape of admixture and evolutionary history of Sherpa people based on the shared alleles and haplotypes from the low-density forensic markers 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.

genetics↗

bioRxiv2021

New insights from the combined discrimination of modern/ancient genome-wide shared alleles and haplotypes: Differentiated demographic history reconstruction of Tai-Kadai and Sinitic people in South China

Southern China was a region with mixed rice-millet farming during the Middle Neolithic period and also suggested to be the homeland of Tai-Kadai-speaking (TK) people. The archaeological evidence of animal and plant domestication has demonstrated that southern Chinese rice agriculturalists dispersed from the Yangtze River basin with the dissemination of TK, Austroasiatic (AA), Austronesian (AN) and Hmong-Mien (HM) languages. However, the formations of the inland TK-speaking people, central/southern Han Chinese and their relationships with Neolithic farmers from the Yangtze and Yellow Rivers (YR) basins are far from clear due to the limited sampling of South China. Here, we revealed the spatiotemporal demographic history of southern China by analyzing newly generated genome-wide data of 70 southeastern mainland TK speakers including Dong, Gelao and Bouyei and 45 southwestern Han Chinese together with comprehensive modern/ancient reference datasets. Southwest Han Chinese and Gelao demonstrated a closer genomic affinity to Neolithic YR farmers, while inland TKs (Dong and Bouyei) demonstrated a closer genomic affinity to coastal TK/AN-speaking islanders and Neolithic Yangtze farmers and their descendants. The shared genetic drift between inland TK/AN speaker highlighted a common origin of AN/TK groups, which may be descended from Tanshishan people or their predecessors (Xitoucun). Additionally, we found that inland TK/Sinitic could be modelled as an admixture of ancestral northern East Asian (ANEA) and ancestral southern East Asian (ASEA) sources with different proportions, in which the ANEA was phylogenetically closer to Neolithic millet farmers deriving from the YR Basin and the ASEA was phylogenetically closer to Coastal Neolithic-to-modern southern East Asians. Finally, we discovered genetic differentiation among TK people from southern China and Southeast Asia and obvious substructures between northern and southern inland Chinese TK people. The observed patterns of the spatiotemporal distribution of the northern and southern East Asian lineages in Central/southern China were also compatible with the scenario of bi-directional gene flow events from ANEA and ASEA. Conclusively, multiple lines of genomic evidence indicated millet farmers deriving from the YR basin and rice farmers deriving from the Yangtze River basin substantially contributed to the present-day mainland TK speakers and Central/southern Han Chinese, and formed the modern dual genetic admixture profile.

genetics↗

bioRxiv2021

A de novo protein structure prediction by iterative partition sampling, topology adjustment, and residue-level distance deviation optimization

MotivationWith the great progress of deep learning-based inter-residue contact/distance prediction, the discrete space formed by fragment assembly cannot satisfy the distance constraint well. Thus, the optimal solution of the continuous space may not be achieved. Designing an effective closed-loop continuous dihedral angle optimization strategy that complements the discrete fragment assembly is crucial to improve the performance of the distance-assisted fragment assembly method. ResultsIn this article, we proposed a de novo protein structure prediction method called IPTDFold based on closed-loop iterative partition sampling, topology adjustment and residue-level distance deviation optimization. First, local dihedral angle crossover and mutation operators are designed to explore the conformational space extensively and achieve information exchange between the conformations in the population. Then, the dihedral angle rotation model of loop region with partial inter-residue distance constraints is constructed, and the rotation angle satisfying the constraints is obtained by differential evolution algorithm, so as to adjust the spatial position relationship between the secondary structures. Lastly, the residue distance deviation is evaluated according to the difference between the conformation and the predicted distance, and the dihedral angle of the residue is optimized with biased probability. The final model is generated by iterating the above three steps. IPTDFold is tested on 462 benchmark proteins, 24 FM targets of CASP13, and 20 FM targets of CASP14. Results show that IPTDFold is significantly superior to the distance-assisted fragment assembly method Rosetta_D (Rosetta with distance). In particular, the prediction accuracy of IPTDFold does not decrease as the length of the protein increases. When using the same FastRelax protocol, the prediction accuracy of IPTDFold is significantly superior to that of trRosetta without orientation constraints, and is equivalent to that of the full version of trRosetta. AvailabilityThe source code and executable are freely available at https://github.com/iobio-zjut/IPTDFold. Contactzgj@zjut.edu.cn

bioinformatics↗

bioRxiv2021

Evolutionary priming and transition to the ectomycorrhizal habit in an iconic lineage of mushroom-forming fungi: is preadaptation a requirement?

The ectomycorrhizal symbiosis is an essential guild of many forested ecosystems and has a dynamic evolutionary history across kingdom Fungi, having independently evolved from diverse types of saprotrophic ancestors. In this study, we seek to identify genomic features of the transition to the ectomycorrhizal habit within the Russulaceae, one of the most diverse lineages of ectomycorrhizal fungi. We present comparative analyses of the pangenome and gene repertoires of 21 species across the order Russulales, including a closely related saprotrophic member of Russulaceae. The ectomycorrhizal Russulaceae is inferred to have originated around the Cretaceous-Paleogene extinction event (73.6-60.1 million years ago (MY)). The genomes of the ectomycorrhizal Russulaceae are characterized by a loss of genes for plant cell-wall degrading enzymes (PCWDEs), an expansion of genome size through increased transposable element (TE) content, a reduction in secondary metabolism clusters, and an association of genes coding for certain secreted proteins with TE "nests". The saprotrophic sister group of the ectomycorrhizal Russulaceae, Gloeopeniophorella convolvens, possesses some of these aspects (e.g., loss of some PCWDE and protease orthologs, TE expansion, reduction in secondary metabolism clusters), resulting from an accelerated rate of gene evolution in the shared ancestor of Russulaceae that predates the evolution of the ectomycorrhizal habit. Genomes of Russulaceae possess a high degree of synteny, including a conserved set of terpene secondary metabolite gene clusters. We hypothesize that the evolution of the ectomycorrhizal habit requires premodification of the genome for plant root association followed by an accelerated rate of gene evolution within the secretome for host-defense circumvention and symbiosis establishment.

evolutionary biology↗

bioRxiv2021

A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation

SummaryWhile SARS-CoV-2 likely has animal origins1, the viral genetic changes necessary to adapt this animal-derived ancestral virus to humans are largely unknown, mostly due to low levels of sequence polymorphism and the notorious difficulties in experimental manipulations of coronavirus genomes. We scanned more than 182,000 SARS-CoV-2 genomes for selective sweep signatures and found that a distinct footprint of positive selection is located around a non-synonymous change (A1114G; T372A) within the Receptor-Binding Domain of the Spike protein, which likely played a critical role in overcoming species barriers and accomplishing interspecies transmission from animals to humans. Structural analysis indicated that the substitution of threonine with an alanine in SARS-CoV-2 concomitantly removes a predicted glycosylation site at N370, resulting in more favorable binding predictions to human ACE2, the cellular receptor. Using a novel bacteria-free cloning system for manipulating RNA virus genomes, we experimentally validated that this SARS-CoV-2-unique substitution significantly increases replication in human cells relative to its putative ancestral variant. Notably, this mutations impact on virus replication in human cells was much greater than that of the Spike D614G mutant, which has been widely reported to have been selected for during human-to-human transmission2,3.

microbiology↗

bioRxiv2021

Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics

Microbial biosynthetic gene clusters (BGCs) encoding secondary metabolites are thought to impact a plethora of biologically mediated environmental processes, yet their discovery and functional characterization in natural microbiomes remains challenging. Here we describe deep long-read sequencing and assembly of metagenomes from biological soil crusts, a group of soil communities that are rich in BGCs. Taking advantage of the unusually long assemblies produced by this approach, we recovered nearly 3,000 BGCs for analysis, including 695 novel, full-length BGCs. Functional exploration through metatranscriptome analysis of a 3-day wetting experiment uncovered phylum-specific BGC expression upon activation from dormancy, elucidating distinct roles and complex phylogenetic and temporal dynamics in wetting processes. For example, a pronounced increase in BGC transcription occurs at night in cyanobacteria but not in other phyla, implicating BGCs in nutrient scavenging roles and niche competition. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional dynamics of BGCs in environmental processes and suggests a central role of secondary metabolites in maintaining phylogenetically conserved niches within biocrusts.

genomics↗

bioRxiv2021

Significant East Asian affinity of Chinese Hui genomic structure suggesting their predominant cultural diffusion model in the genetic formation process

Ancestral origin and genomic history of Chinese Hui people remain to be explored due to the paucity of genome-wide data. Some evidence argued that an eastward migration of Central Asian given rise to modern Hui people, which was inferred as the demic diffusion hypothesis, and others favored the cultural diffusion hypothesis that posited indigenous East Asian adopted Muslim-like culture and formed the modern culturally different populations. However, the extent to which the observed Huis genetic structure was mediated by the movement of people or the assimilation of Muslim culture also remains one of the most contentious puzzles. Analyses of over 700K SNPs in 109 western Chinese individuals (49 Sichuan Hui and 60 geographically close Nanchong Han) together with the available ancient and modern Eurasians allowed us to fully explore the genomic makeup and origin of Huis and neighboring Hans. The results of the traditional and formal admixture-statistics (PCA, ADMIXTURE, and allele-sharing-based f-statistics) illuminated a strong genomic affinity between Sichuan Hui and Neolithic-to-modern Northern East Asians, which suggested massive gene influx from East Asian into Sichuan Hui people. Three-way admixture models in the qpWave/qpAdm analyses further revealed a small stream of gene influx from western Eurasian related to French or Andronovo into these Hui people, which was further directly confirmed via the admixture event from the temporally different western sources to Hui people in the qpGraph-based phylogenetic model, suggesting the key role of cultural diffusion model in the genetic formation of the modern East Asian Hui. ALDER-based admixture date estimation showed that this observed western Eurasian admixture signal was introduced into East Asian Hui during the historic periods, concordant with the extensive western-eastern communication in the Silk Road and historically documented Huis migration history. Summarily, although significant cultural differentiation among Hui and their neighbors existed, our genomic analysis showed their strong affinity with modern and ancient Northern East Asians. Our results supported that modern Chinese Hui arose from the mixture of minor western Eurasian ancestry and predominantly East Asian ancestry.

genetics↗

bioRxiv2020

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.

genetics↗

bioRxiv2020

3D Genome Contributes to Protein-Protein Interactome

Numerous computational methods have been proposed to predict protein-protein interactions, none of which however, considers the original DNA loci of the interacting proteins in the perspective of 3D genome. Here we retrospect the DNA origins of the interacting proteins in the context of 3D genome and discovered that 1) if a gene pair is more proximate in 3D genome, their corresponding proteins are more likely to interact. 2) signal peptide involvement of PPI affects the corresponding gene-gene proximity in 3D genome space. 3) by incorporating 3D genome information, existing PPI prediction methods can be further improved in terms of accuracy. Combining our previous discoveries, we conjecture the existence of 3D genome driven cellular compartmentalization, meaning the co-localization of DNA elements lead to increased probability of the co-localization of RNA elements and protein elements.

bioinformatics↗

bioRxiv2020

Genomic Insights into the Demographic History of Southern Chinese

Southern China is the birthplace of rice-cultivating agriculture, different language families, and human migrations that facilitated these cultural diffusions. The fine-scale demographic history in situ, however, remains unclear. To comprehensively cover the genetic diversity in East and Southeast Asia, we generated genome-wide SNP data from 211 present-day Southern Chinese and co-analyzed them with more than 1,200 ancient and modern genomes. We discover that the previously described Southern East Asian or Yangtze River Farmer lineage is monophyletic but not homogeneous, comprising four regionally differentiated sub-ancestries. These ancestries are respectively responsible for the transmission of Austronesian, Kra-Dai, Hmong-Mien, and Austroasiatic languages and their original homelands successively distributed from East to West in Southern China. Multiple phylogenetic analyses support that the earliest living branching among East Asian-related populations is First Americans ([~]27,700 BP), followed by the pre-LGM differentiation between Northern and Southern East Asians ([~]23,400 BP) and the pre-Neolithic split between Coastal and Inland Southern East Asians ([~]16,400 BP). In North China, distinct coastal and inland routes of south-to-north gene flow had established by the Holocene, and further migration and admixture formed the genetic profile of Sinitic speakers by [~]4,000 BP. Four subsequent massive migrations finalized the complete genetic structure of present-day Southern Chinese. First, a southward Sinitic migration and the admixture with Kra-Dai speakers formed the Sinitic Cline. Second, a bi-directional admixture between Hmong-Mien and Kra-Dai speakers gave rise to the Hmong-Mien Cline in the interior of South China between [~]2,000 and [~]1,000 BP. Third, a southwestward migration of Kra-Dai speakers in recent [~]2,000 years impacted the genetic profile for the majority of Mainland Southeast Asians. Finally, an admixture between Tibeto-Burman incomers and indigenous Austroasiatic speakers formed the Tibeto-Burman speakers in Southeast Asia by [~]2,000 BP.

genomics↗