East Asian Lineage Research Articles

Genetic diversity, evolution and drug resistance of Mycobacterium tuberculosis lineage 2.

Mycobacterium tuberculosis causes a chronic infectious disease called tuberculosis. Phylogenetic lineage 2 (L2) of M. tuberculosis, also known as the East Asian lineage, is associated with high virulence, increased transmissibility, and the spread of multidrug-resistant strains. This review article examines the genomic characteristics of the M. tuberculosis genome and M. tuberculosis lineage 2, such as the unique insertion sequence and spoligotype patterns, as well as MIRU-VNTR typing, and SNP-based barcoding. The review describes the geographical distribution of lineage 2 and its history of origin. In addition, the article discusses recent studies on drug resistance and compensatory mechanisms of M. tuberculosis lineage 2 and its impact on the pathogen's transmissibility and virulence. This review article discusses the importance of establishing a unified classification for lineage 2 to ensure consistency in terminology and criteria across different studies and settings.

Genetic diversity of Mycobacterium tuberculosis strains isolated from spiritual holy water site attendees in Northwest Ethiopia. A cross-sectional study

BackgroundThe genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains was characterized among isolates from individuals with pulmonary tuberculosis (PTB) symptoms attended holy water sites (HWSs) in the Amhara region, Ethiopia. MethodsA cross-sectional study was done from June 2019 to March 2020 to describe the genetic diversity and drug-resistance profiles of MTBC isolates. Sputum specimens were collected and cultured in the Löwenstein-Jensen culture medium. Line Probe Assay, MTBDRplus VER 2.0, and MTBDRsl VER 2.0 were used to detect first-and second-line anti-TB drug-resistance patterns. A spoligotyping technique was utilized to characterize the genetic diversity. Statistical analysis was performed using STATA 15. ResultsOf 560 PTB-symptomatic participants, 122 (21.8%) were culture-positive cases. Spoligotyping of 116 isolates revealed diverse MTBC sublineages, with four major lineages: Euro-American (EA) (Lineage 4), East-African-Indian (EAI) (Lineage 3), Ethiopian (ETH) (Lineage 7), East Asian (EA) (Lineage 2). The majority (96.6%) of the isolates were EA (lineage 4) and EAI, with proportions of 54.3% and 42.2%, respectively. A total of 31 spoligotype patterns were identified, 26 of which were documented in the SITVIT2 database. Of these, there were 15 unique spoligotypes, while eleven were grouped with 2-17 isolates. SIT149/T3-ETH (n = 17), SIT26/CAS1-DELHI (n = 16), SIT25/CAS1-DELHI (n = 12), and SIT52/T2 (n = 11) spoligotypes were predominant. A rare spoligotype pattern: SIT41/Turkey and SIT1/Beijing, has also been identified in North Shewa. The overall clustering rate of sub-lineages with known SIT was 76.4%.Of the 122 culture-positive isolates tested, 16.4% were resistant to rifampicin (RIF) and/or isoniazid (INH). Multidrug-resistant TB (MDR-TB) was detected in 12.3% of isolates, five of which were fluoroquinolones (FLQs) resistant. SIT149/T3-ETH and SIT21/CAS1-KILI sublineages showed a higher proportion of drug resistance. ConclusionsDiverse MTBC spoligotypes were identified, with the T and CAS families and EA (lineage 4) predominating. A high prevalence of drug-resistant TB, with SIT149/T3-ETH and CAS1-KILI sublineages comprising a greater share, was observed. A study with large sample size and a sequencing method with stronger discriminatory power is warranted to understand better the genetic diversity of circulating MTBC in this cohort of study, which would help to adopt targeted interventions.

Salvia guidongensis sp. nov.: unraveling a critical evolutionary link in East Asian Salvia from Central China integrating morphology, phylogeny, and plastid genomics.

Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus. Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia. The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics. The newly discovered species, Salvia guidongensis, exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria, S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia, suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis, comparing them with those of closely related species. The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia.

ADAPTATION TO MULTISTRESS IN VITRO OF MYCOBACTERIUM TUBERCULOSIS STRAINS OF EAST-ASIAN AND EURO-AMERICAN LINEAGES, DIFFERING IN DRUG RESISTANCE

In order to study the in vitro adaptation of M.tuberculosis strains of various phylogenetic lineages and drug resistance under multistress conditions created by a lack of nutrients, reactive forms of nitrogen and oxygen, 17 strains of M.tuberculosis were studied (10 strains of the East Asian lineage of the Beijing sublineage and 7 strains Euro-American lineage). We studied the culture yield, the state of M.tuberculosis cells in culture and the secretome when cultivating strains under conditions of multistress, nitrosative stress and in optimal conditions. It has been established that M. tuberculosis strains of frequently SITs with a sensitive genotype or with widespread mutations, in contrast to strains with rare mutations and with an expanded spectrum of phenotypic drug resistance, adapt well to stress conditions in vitro. M.tuberculosis strains of the Beijing sublineage adapt to stress at an earlier time than M.tuberculosis of the Euro-American lineage; this was especially evident in the multistress model.

Genetic diversity of Mycobacterium tuberculosis isolates from the central, eastern and southeastern Ethiopia

IntroductionThe population structure of Mycobacterium tuberculosis complex (MTBC) in Ethiopia is diverse but dominated by Euro-American (Lineage 4) and East-African-Indian (Lineage 3) lineages. The objective of this study was to describe the genetic diversity of MTBC isolates in Central, Eastern and Southeastern Ethiopia. MethodsA total of 223 MTBC culture isolates obtained from patients referred to Adama and Harar TB reference laboratories were spoligotyped. Demographic and clinical characteristics were collected. ResultsSix major lineages: Euro-American (Lineage 4), East-African-Indian (Lineage 3), East Asian (Lineage 2), Indo-Oceanic (Lineage 1), Mycobacterium africanum (Lineage 5 and Lineage 6) and Ethiopian (Lineage 7) were identified. The majority (94.6 %) of the isolates were Euro-American and East-African-Indian, with proportions of 75.3 % and 19.3 %, respectively. Overall, 77 different spoligotype patterns were identified of which 42 were registered in the SITVIT2 database. Of these, 27 spoligotypes were unique, while 15 were clustered with 2–49 isolates. SIT149/T3_ETH (n = 49), SIT53/T1 (n = 33), SIT21/CAS1_Kili (n = 24) and SIT41/Turkey (n = 11) were the dominant spoligotypes. A rare Beijing spoligotype pattern, SIT541, has also been identified in Eastern Ethiopia. The overall clustering rate of sub-lineages with known SIT was 71.3 %. Age group (25–34) was significantly associated with clustering. ConclusionWe found a heterogeneous population structure of MTBC dominated by T and CAS families, and the Euro-American lineage. The identification of the Beijing strain, particularly the rare SIT541 spoligotype in Eastern Ethiopia, warrants a heightened surveillance plan, as little is known about this genotype. A large-scale investigation utilizing a tool with superior discriminatory power, such as whole genome sequencing, is necessary to gain a thorough understanding of the genetic diversity of MTBC in the nation, which would help direct the overall control efforts.

Genetic differentiation and species diversification of the Adoxophyes orana complex (Lepidoptera: Tortricidae) in East Asia.

The Adoxophyes tea tortrix (Lepidoptera: Tortricidae) is a group of leaf rollers that cause enormous economic losses on tea and apple crops. In East Asia, taxonomic ambiguity of the Adoxophyes orana complex (AOC), which consists of A. orana, A. dubia, A. honmai, and A. paraorana, has persisted for decades because of vague diagnostic characters. In this study, differences in the AOC were examined to improve species identification, determine genetic variations, and develop control strategies. Analyses revealed that A. orana comprised 2 lineages, a widely distributed Palearctic lineage and an East Asian lineage that was nested with other Asian species. Genetic divergence of >3% is proposed to confirm the AOC species that would benefit subsequent taxonomic revision. The monophyletic Taiwanese A. sp. with 2.8-4% from other AOC species appeared to suggest it as an independent taxon, and low interspecific divergence between A. honmai and A. dubia of 0.3% indicated possibility of recent divergence or intraspecific variations. Our result further suggested that the Z9-14:Ac ratio of semiochemicals could be a reference for the reblending of pheromone attractants in Taiwanese tea plantations. Moreover, the AOC species appeared to have a tendency of specific geographic distributions, with A. dubia and A. honmai in Japan and China, A. paraorana in Korea, and A. sp. in Taiwan. Maintaining the unique genetic composition of Adoxophyes species in each geographic region and preventing the possible invasions into those AOC-free countries through the transportation of host plants are essential in managing the AOC in East Asia.

Whole-Genome Sequencing of Mycobacterium tuberculosis Isolates from Diabetic and Non-Diabetic Patients with Pulmonary Tuberculosis.

The association of tuberculosis and type 2 diabetes mellitus has been a recognized re-emerging challenge in management of the convergence of the two epidemics. Though much of the literature has studied this association, there is less knowledge in the field of genetic diversities that might occur in strains infecting tuberculosis patients with and without diabetes. Our study focused on determining the extent of diversity of genotypes of Mycobacterium tuberculosis in both these categories of patients. We subjected 55 M. tuberculosis isolates from patients diagnosed with pulmonary TB with and without type 2 diabetes mellitus to whole-genome sequencing on Illumina Hi Seq platform. The most common lineage identified was lineage 1, the Indo-Oceanic lineage (n = 22%), followed by lineage 4, the Euro-American lineage (n = 18, 33%); lineage 3, the East-African Indian lineage (n = 13, 24%); and lineage 2, the East-Asian lineage (n = 1, 2%). There were no significant differences in the distribution of lineages in both diabetics and non-diabetics in the South Indian population, and further studies involving computational analysis and comparative transcriptomics are needed to provide deeper insights.

Crocodylian princess in Taiwan: Revising the taxonomic status of Tomistoma taiwanicus from the Pleistocene of Taiwan and its paleobiogeographic implications

AbstractToyotamaphimeia is an extinct crocodylian lineage whose name is derived from a mythological Japanese princess. Here, we re-examine the type specimens of a long-forgotten species: Tomistoma taiwanicus from the Pleistocene of Tainan (Taiwan) and revise its taxonomic status to Toyotamaphimeia taiwanicus n. comb., leading to the first recognized species of Toyotamaphimeia outside Japan. Our phylogenetic analyses also support this taxonomic assignment and, more interestingly, further suggest an East Asian lineage. In addition, Toyotamaphimeia taiwanicus n. comb. represents a tropical species, resolving a long-standing puzzle of why Toyotamaphimeia only inhabited a much higher latitudinal area (Japan). Given the large body size of Toyotamaphimeia taiwanicus n. comb. (~7 m) and the fact that it is geologically older than Toyotamaphimeia machikanensis from Japan, we propose a novel evolutionary scenario: the genus Toyotamaphimeia originated in Taiwan and evolved to a large body size with gigantothermic physiology, which resulted in migration out of Taiwan and dispersal farther north to Japan. Our taxonomic identification shows the presence of an extinct endemic crocodylian species from the Pleistocene of Taiwan with large-scale paleogeographic implications. This study, with our recent progress in vertebrate paleontology in Taiwan, should provoke more in-depth paleontological research on the Pleistocene extinction.

Whole genome characterization and evolutionary analysis of bovine ephemeral fever virus isolated in Iran.

Bovine ephemeral fever virus (BEFV) is an economically important arthropod-borne virus of cattle and water buffaloes which is enzootic in Africa, Australia, and Asia. We characterized the entire length of BEFV BA/RZ/IR strain genome isolated in Iran and compared to the all BEFV full genomes available in the GenBank. The BEFV genomes were phylogenetically classified as 4 lineages including the Middle Eastern, East Asian, Australian, and South African lineages. The Iranian BA/RZ/IR strain, which displayed maximum sequence identity (96.72%) to the Chinese JT02L strain was clustered as a separate branch in the East Asian lineage of the virus. Using Shannon entropy analysis, amino acid variations were detected in the all proteins encoded by BEFV genomes. Particularly, the polymerase L and the accessory proteins Gns, α2 and β exhibited the highest amino acid variations suggesting their significance in the viral replication efficiency. Our bioinformatics analyses also predict the occurrence of recombination event within the East Asian lineage of BEFV genomes. Our data show that the Chinese Henan 1 may be a hybrid strain constructed of the Chinese JT02L and Iranian BA/RZ/IR BEFV strains as the major and minor parents, respectively. These computational analyses suggest that the homologous recombination may be an evolutionary mechanism for BEFV as a member of the Rhabdoviridae family.

PncA Large Deletion is the Characteristic of Pyrazinamide-Resistant Mycobacterium tuberculosis belonging to the East Asian Lineage.

Pyrazinamide (PZA) is often used as an add-on agent in the treatment of multidrug-resistant tuberculosis, regardless of phenotypic drug susceptibility testing (pDST) results. However, evaluating the effectiveness of PZA is challenging because of its low pH activity, which can result in unreliable pDST results. This study aimed to investigate the genomic characteristics associated with PZA resistance that can be used to develop genotypic DST. A publicly available whole genome sequencing (WGS) dataset of 10,725 Mycobacterium tuberculosis complex genomes (3,326 phenotypically PZA-resistant and 7,399 phenotypically PZA-susceptible isolates) were analyzed. In total, 2,934 pncA non-silent mutations were identified in 2,880 isolates (26.9%). Detected mutations were found throughout the entire coding region of pncA in a scattered pattern, of which the most frequent mutation was p.Q10P (n = 278), followed by p.H57D (n = 167) and c.-11A>G (n = 122). The sensitivity and specificity of the group 1 or 2 mutations reported by the World Health Organization (WHO) mutational catalogue were 73.0% and 98.9%, respectively. We further identified 18 novel pncA mutations that were significantly associated with phenotypically PZA-resistant. In addition to these mutations, we identified 102 large deletions in the pncA gene, and all but two isolates were phenotypically resistant to PZA isolates. Notably, pncA deletions were mutually exclusive to pncA mutations, and more than half of the isolates with pncA large deletions belonged to the East Asian lineage (67.6%). The sensitivity, specificity, positive predictive value, and negative predictive value of the pooled variants (group 1 or 2 mutations, novel resistance-associated mutations, and large deletions of the pncA gene) were 79.0%, 98.9%, 97.0%, and 91.3%, respectively. The area under the curve (AUC) value for the pooled variants was significantly higher than the AUC value for the group 1 or 2 mutations (P <0.001), indicating that the pooled variants have a better discriminative ability for predicting PZA resistance. Using WGS, we found that the pncA mutations are scattered without specific mutational hotspots, and large deletions associated with PZA resistance are more common in the East Asian lineage of M. tuberculosis isolates. Our data also demonstrated the reliability of group 1 or 2 mutations presented in the WHO mutation catalogue and the need for further investigation on group 3 mutations, contributing to the evaluation of the current knowledge base on mutations associated with the PZA-resistant M. tuberculosis complex.

Niche evolution versus niche conservatism and habitat loss determine persistence and extirpation in late Neogene European Fagaceae

An increasing body of palaeobotanical data demonstrates a series of Pliocene and Pleistocene extirpations and extinctions of plant lineages in western Eurasia, which are believed to have been determined by the climatic properties of their related East Asian and North American sister lineages. We investigated the diversity of a widespread northern hemispheric plant family, Fagaceae, during the Late Pliocene of Portugal. We found a high diversity of Fagaceae comprising extant and extinct lineages. Dispersed pollen of Castanopsis and Quercus sect. Cyclobalanopsis represent the youngest records of these Himalayan-Southeast Asian groups in western Eurasia. Likewise, fossil-species of Quercus sect. Lobatae and the North American clade of sect. Quercus are the youngest records of these modern New World groups in western Eurasia. For the extinct Trigonobalanopsis, the pollen record of Portugal is the youngest known of this genus. Climate data of modern representatives demonstrate that a deterministic model can explain only a part of the Pliocene and Pleistocene extirpations. Modern cold month mean temperatures of Castanopsis and Quercus sect. Cyclobalanopsis and their last occurrences in western Eurasia in the Pliocene fit with a deterministic model (niche conservatism). In contrast, survival or extirpation of groups with high cold tolerance appear to have been more complex. Here, niche evolution, abundance and diversity of a lineage during pre-Pleistocene times, and habitat availability/loss determined the fate of Fagaceae lineages in western Eurasia.

Evolutionary history of theAsplenium scolopendriumcomplex (Aspleniaceae), a relictual fern with a northern pan-temperate disjunct distribution

AbstractAsplenium scolopendrium is distributed in northern temperate forests with many global biogeographic disjunctions. The species complex of A. scolopendrium has been generated by spatial segregation coupled with divergent evolution. We elucidated the biogeographic history of the A. scolopendrium complex by exploring its origin, dispersal and evolution, thus providing insights into the evolutionary history of the Tertiary floras with northern pan-temperate disjunct distributions. The results revealed that all infraspecific taxa descended from a widely distributed common ancestor in the Northern Hemisphere. This pan-temperate ancestral population formed by unidirectional westward dispersal from European origins primarily during the Early Eocene when the Earth’s climate was much warmer than today. The splitting of European, American and East Asian lineages occurred during the Early Miocene due to geo-climatic vicariances. Polyploidy events in the American ancestral populations created additional reproductive barriers. The star-shaped haplotypes in each continent indicated that local disjunctions also led to derived genotypes with potential to diverge into different taxa. This intracontinental lineage splitting is likely related to latitudinal range shift and habitat fragmentation caused by glacial cycles and climate change during the Pleistocene. The evolutionary history of the A. scolopendrium complex supported the Boreotropical hypothesis exhibiting range expansion during the Early Eocene Climatic Optimum.

Uniparental Genetic Analyses Reveal Multi-Ethnic Background of Dunhuang Foyemiaowan Population (220–907 CE) With Typical Han Chinese Archaological Culture

The relationship between archeological culture and ethnicity is invariably complex. This is especially the case for periods of national division and rapid inter-ethnic exchange, such as China’s Sixteen Kingdoms (304–439 CE) and Northern and Southern Dynasties (420–589 CE). Going by tomb shape and grave goods, the Foyemiaowan cemetery at Dunhuang exhibits a typical third–tenth century Han style. Despite this, the ethnic makeup of the Foyemiaowan population has remained unclear. We therefore analyzed 485 Y-chromosomal SNPs and entire mitochondrial genomes of 34 Foyemiaowan samples. Our study yielded the following discoveries: (1) principal component analysis revealed that the Foyemiaowan population was closely clustered with Tibeto-Burman populations on the paternal side and close to Mongolic-speaking populations on the maternal side; (2) lineage comparisons at the individual level showed that the Foyemiaowan population consisted of primarily Tibeto-Burman and Han Chinese related lineages (Oα-M117, 25%;Oβ-F46, 18.75%), partially Altaic speaking North Eurasian lineages (N-F1206, 18.75%) and a slight admixture of southern East Asian lineages (O1b1a2-Page59, 6.25%; O1b1a1-PK4, 3.13%). Similarly, the maternal gene pool of Foyemiaowan contained northern East Asian (A, 4.17%; CZ, 16.67%; D, 20.83%; G, 4.17%; M9, 4.17%), southern East Asian (B, 12.51%; F, 20.83%) and western Eurasian (H, 4.17%; J, 4.17%) related lineages; (3) we discovered a relatively high genetic diversity among the Foyemiaowan population (0.891) in our ancient reference populations, indicating a complex history of population admixture. Archeological findings, stable isotope analysis and historical documents further corroborated our results. Although in this period China’s central government had relinquished control of the Hexi Corridor and regional non-Han regimes became the dominant regional power, Foyemiaowan’s inhabitants remained strongly influenced by Han culture.

Country-wide genotyping of Mycobacterium tuberculosis complex in Singapore, 2011–2017

ObjectiveTo describe the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) and factors associated with its transmission in Singapore. MethodsSpoligotyping, 24-loci mycobacterial interspersed repetitive units – variable number of tandem repeats (MIRU-VNTR) typing and demographic data from the national TB notification registry of MTBC culture-positive cases notified from January 2011 to December 2017 were analysed. ResultsOf the 12,046 culture-positive cases notified, complete spoligotyping and MIRU-VNTR typing results were available for 8690 (72.1%) belonging to 4950 (57.0%) local-born and 3740 (43.0%) foreign-born persons. From these, 4810 (55.3%) were identified in 883 clusters. The proportion of recent transmission was 45.2%. The East-Asian Lineage 2 accounted for 4045 (47.1%) of isolates, and disproportionately accounted for large clusters. Clustered cases were more likely to be older than 50 years, male, Malay, local-born, Singapore citizens or Permanent Residents, of lower socioeconomic status, imprisoned; to harbour East-Asian Lineage 2 strain; to have cavitary pulmonary TB, positive sputum smear or be recalcitrant treatment defaulters. They were less likely to have multidrug-resistant, or isoniazid or rifampicin mono-resistant TB. ConclusionWe demonstrated the diversity of MTBC strains and, notwithstanding the likely over-estimation of clustering using these genotyping methods, elucidated factors associated with TB transmission in Singapore.

Contrasting maternal and paternal genetic histories among five ethnic groups from Khyber Pakhtunkhwa, Pakistan

Northwest Pakistan has served as a point of entry to South Asia for different populations since ancient times. However, relatively little is known about the population genetic history of the people residing within this region. To better understand human dispersal in the region within the broader history of the subcontinent, we analyzed mtDNA diversity in 659 and Y-chromosome diversity in 678 individuals, respectively, from five ethnic groups (Gujars, Jadoons, Syeds, Tanolis and Yousafzais), from Swabi and Buner Districts, Khyber Pakhtunkhwa Province, Pakistan. The mtDNAs of all individuals were subject to control region sequencing and SNP genotyping, while Y-chromosomes were analyzed using 54 SNPs and 19 STR loci. The majority of the mtDNAs belonged to West Eurasian haplogroups, with the rest belonging to either South or East Asian lineages. Four of the five Pakistani populations (Gujars, Jadoons, Syeds, Yousafzais) possessed strong maternal genetic affinities with other Pakistani and Central Asian populations, whereas one (Tanolis) did not. Four haplogroups (R1a, R1b, O3, L) among the 11 Y-chromosome lineages observed among these five ethnic groups contributed substantially to their paternal genetic makeup. Gujars, Syeds and Yousafzais showed strong paternal genetic affinities with other Pakistani and Central Asian populations, whereas Jadoons and Tanolis had close affinities with Turkmen populations from Central Asia and ethnic groups from northeast India. We evaluate these genetic data in the context of historical and archeological evidence to test different hypotheses concerning their origins and biological relationships.

Evaluation of Five User-Friendly Whole Genome Sequencing Software for Mycobacterium tuberculosis in Clinical Application.

Whole genome sequencing (WGS) is an increasingly useful tool for tuberculosis (TB) diagnosis and disease management. In this study, we evaluated the utility of user-friendly WGS tools in reporting resistance profiles and identifying lineages of clinical TB isolates from South Korea. Forty clinical samples from TB patients showing discrepancies between their rapid molecular and conventional drug susceptibility tests were used in this study. Among these clinical isolates, 37 strains were successfully evaluated via WGS software, using the GenTB, TB Profiler, PhyResSE, CASTB, and Mykrobe. More accurate and faster susceptibility results could be obtained with isoniazid than with rifampin. Using the phenotypic test as the gold standard, the isoniazid concordance rate between phenotypic drug susceptibility test (DST) and WGS (GenTB: 45.9%, TB profiler: 40.5%, PhyResSE: 40.5%, CASTB: 48.6%, and Mykrobe: 43.2%) was much higher than between phenotypic DST and rapid molecular genotypic DST (18.9%) among the 37 strains. In contrast, the rifampin concordance rate between phenotypic DST and WGS and that between phenotypic DST and rapid molecular genotypic DST was similar (81.1-89.2%). We also found novel mutations associated with INH in katG and ahpC gene region, not covered by the line probe assay. In addition, lineage analysis identified 81.1% of these samples as L2 East Asian lineage strains, and 18.9% as L4 Euro-American lineage strains. WGS may play a pivotal role in TB diagnosis and the detection of drug resistance, genetic diversity, and transmission dynamics in the near future because of its accuracy, speed, and extensibility.

The genomic history of southwestern Chinese populations demonstrated massive population migration and admixture among proto-Hmong-Mien speakers and incoming migrants.

Southwest China was the crossroad for the initial settler people of East Asia, which shows the highest diversity in languages and genetics. This region played a significant role in the formation of the genetic makeup of the proto-Hmong-Mien-speaking people and in the north-to-south human expansion during the Neolithic-to-historic transformation. Their genetic history covering migration events and the admixture processes still needs to be further explored. Therefore, in the current study, we have generated genome-wide data from three genomic aspects covering autosomal, mitochondrial and Y-chromosomal regions in 260 Hmong-Mien, Tibeto-Burman, and Sinitic people from 29 different southwestern Chinese groups, and further analyzed them with 2676 published modern and ancient Eurasian genomes. Here, we have noticed a new southwestern East Asian genetic cline composed of the Hmong-Mien-specific ancestry enrichedin modern Hmong and Pathen. This newly identified southern inland East Asian lineage contributed to a great extent of the gene pool in the modern southern East Asians. We also have observed genetic substructure among Hmong-Mien-speaking populations. The southern Hmong-Mien-speaking people showed more genetic affinity with modern Tai-Kadai/Austroasiatic people, while the northern Hmong-Mien speakers expressed a closer genetic connection with the Neolithic-to-modern northern East Asians. Moreover, southwestern Sinitic populations had a strong genomic affinity with the adjacent Hmong-Mien-speaking populations and the lowlander Tibeto-Burman-speaking populations, which suggested the large-scale genetic admixture occurred between them. Allele-sharing-based qpAdm/qpGraph results further confirmed that all included southwestern Chinese populations could be modeled as a mixed result of the major ancestry component from the northern millet farmers in the Yellow River basin and the minor ancestry component from the southern rice farmers in the Yangtze River basin. Usually, this newly identified Hmong-Mien-associated southern East Asian ancestry could improve our understanding of the full-scale genetic landscape of the evolutionary and admixture history of southwestern East Asians. Further ancient genomic studies from southeastern China are required to shed deeper light on our established phylogeny context.

Beringia and the Settlement of the Western Hemisphere

Previously, we addressed the problem of what variable(s) limited widespread human settlement of the Americas before ~15 ka. We concluded that while non-modern human taxa (e. g., Neanderthals) probably did not inhabit high-latitude environments (due to cold climate and/ or low plant and animal productivity) and thus could not disperse in the Western Hemispherevia Beringia, modern humans likely were denied access to mid-latitude North America &gt;15 ka by coastal and interior ice sheets. Here we reexamine the problem with respect to modern humans in light of a revised chronology for glaciers and sea level, new research in paleo-genomics, and some new archaeological discoveries. During 35–30 ka, a lineage with west Eurasian roots occupied the Great Arctic Plain and may have expanded into eastern arctic Beringia and mid-latitude North America via an ice-free corridor. An East Asian lineage associated with microblade technology occupied the Lena Basin during the LGM and expanded onto the Great Arctic Plain &gt;15 ka, possibly as early as the GI 2 interstadial (24–23 ka). Their immediate descendants probably occupied the southern Bering Land Bridge and Northwest Pacific coast &gt;15 ka and dispersed widely in the Western Hemisphere during GI 1 (14.5–12.9 ka), primarily if not exclusively via a coastal route. The coalesced Laurentide and Cordilleran ice sheets blocked interior access to mid-latitude America until 13.8 ± 0.5 ka (and possibly later due to the length and narrow width of the ice-free corridor &gt;13 ka).

Massive cranium from Harbin in northeastern China establishes a new Middle Pleistocene human lineage

It has recently become clear that several human lineages coexisted with Homo sapiens during the late Middle and Late Pleistocene. Here, we report an archaic human fossil that throws new light on debates concerning the diversification of the Homo genus and the origin of H. sapiens. The fossil was recovered in Harbin city in northeastern China, with a minimum uranium-series age of 146 ka. This cranium is one of the best preserved Middle Pleistocene human fossils. Its massive size, with a large cranial capacity (∼1,420 mL) falling in the range of modern humans, is combined with a mosaic of primitive and derived characters. It differs from all the other named Homo species by presenting a combination of features, such as long and low cranial vault, a wide and low face, large and almost square orbits, gently curved but massively developed supraorbital torus, flat and low cheekbones with a shallow canine fossa, and a shallow palate with thick alveolar bone supporting very large molars. The excellent preservation of the Harbin cranium advances our understanding of several less-complete late Middle Pleistocene fossils from China, which have been interpreted as local evolutionary intermediates between the earlier species Homo erectus and later H. sapiens. Phylogenetic analyses based on parsimony criteria and Bayesian tip-dating suggest that the Harbin cranium and some other Middle Pleistocene human fossils from China, such as those from Dali and Xiahe, form a third East Asian lineage, which is a part of the sister group of the H. sapiens lineage. Our analyses of such morphologically distinctive archaic human lineages from Asia, Europe, and Africa suggest that the diversification of the Homo genus may have had a much deeper timescale than previously presumed. Sympatric isolation of small populations combined with stochastic long-distance dispersals is the best fitting biogeographical model for interpreting the evolution of the Homo genus.

Distribution of Mycobacterium tuberculosis lineages in South America

Molecular genotyping of Mycobacterium tuberculosis allows for the identification of circulating lineages and sublineages in the population and their relationship with migratory movements. The purpose of this review is to describe the phylogeography of Mycobacterium tuberculosis reported in South American countries that was analyzed using genotyping tools, analyze the Tuberculosis hotspots for the region and determine the impact of the COVID-19 pandemic on the Tuberculosis control program. The Latin American Mediterranean (LAM) sublineage belonging to the Euro-American lineage (Lineage 4) presents the highest prevalence in South America and is followed by the Beijing sublineage belonging to the East Asian lineage (Lineage 2). The Beijing sublineage is considered of worldwide interest because of its association with multidrug-resistant tuberculosis (MDR-TB), which is almost entirely distributed in South America, with Peru being the country with the highest prevalence for this sublineage. On the other hand, the Indo-Oceanic (Lineage 1), India-East Asia (Lineage 3) and West- African 2 (Lineage 6) sublineages have been reported with lower prevalence in South America. The molecular techniques used in the genotyping studies for Mycobacterium tuberculosis in South America were as follows: typing by complementary oligonucleotide spacer sequences (Spoligotyping), restriction-hybridization patterns (IS6110-RFLP, PGRS-RFLP), mycobacterial interspaced repeat units-variable number tandem repeats (MIRU-VNTR) and whole genome sequencing (WGS). At present, Brazil and Peru are the hotspots for tuberculosis and MDR-TB in South America, where the control of tuberculosis wholly affected by the COVID-19 pandemic. Thus, there have been significant impacts on containment programs and possible post-pandemic scenarios such that scientific contributions will need to be evaluated and implemented with new strategies for prevention, diagnosis, treatment and control of Tuberculosis.