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Functional E‐cadherin loss, a hallmark of epithelial‐mesenchymal transition (EMT), is important for metastasis. However, the mechanism of Snail2 in hepatocellular carcinoma (HCC) EMT and metastasis remains unclear. Here, we showed that Snail2 was upregulated in primary HCC, and significantly increased during transforming growth factor‐β‐induced liver cell EMT. Snail2‐overexpressing and knockdown cell lines have been established to determine its function in EMT in HCC. H3K9 methylation was upregulated and H3K4 and H3K56 acetylation were downregulated at the E‐cadherin promoter in Snail2‐overexpressing cancer cells. Furthermore, Snail2 interacted with G9a and histone deacetylases (HDACs) to form a complex to suppress E‐cadherin transcription. Snail2 overexpression enhanced migration and invasion in HCC cells, whereas G9a and HDAC inhibition significantly reversed this effect. Moreover, Snail2 overexpression in cancer cells increased tumor metastasis and shortened survival time in mice, whereas G9a and HDAC inhibitors extended survival. Our study not only reveals a critical mechanism underlying the epigenetic regulation of EMT but also suggests novel treatment strategies for HCC. Snail2 was upregulated in hepatocellular carcinoma and lung cancer tissues, and significantly increased during transforming growth factor‐β‐induced liver cell epithelial‐mesenchymal transition. Snail2 interacted with G9a and histone deacetylases to form a complex to suppress E‐cadherin transcription and enhanced migration and invasion in hepatocellular carcinoma cells. Snail2 overexpression in cancer cells increased tumor metastasis and shortened survival time in mice, whereas G9a and histone deacetylase inhibitors extended survival.

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome-wide data from 26 ancient individuals from northern and southern East Asia spanning 9500 to 300 years ago. Genetic differentiation in this region was higher in the past than the present, which reflects a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, thereby transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient individuals with Austronesian-related ancestry, which supports an origin in southern China for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.

Northern China harbored the world’s earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration. Northern China contains some of the world’s earliest farming societies. Here, authors use 55 ancient genomes to trace the genetic history of human migrations across northern China for the last 7500 years, and document genetic changes mirroring shifts in subsistence strategy.

Background Northwestern Xinjiang is situated at the confluence of the central Eurasian Steppe, the Inner Asian Mountain Corridor and the Tianshan mountains, and is home to rich archaeological, cultural and genetic diversity. However, the local population dynamics remain poorly understood due to the lack of time-series ancient DNA data. Results We analyze DNA from ten individuals from the Narensu site in northwestern Xinjiang spanning the Chalcolithic to the Iron Age. Our findings reveal that the earliest inhabitants of northwestern Xinjiang were formed by a genetic admixture of Ancient North Eurasians and Altai hunter-gatherers around 6000 years ago. The simultaneous arrival of ancestry related to the Bactria Margiana Archaeological Complex from Central Asia and Afanasievo-related populations from the Steppe in the early Bronze Age was detected, thereby highlighting the important role of the Inner Asian Mountain Corridor as a migration route between southern Central Asia and Xinjiang. This may also have involved the formation of the Chemurchek population in Altai, northern Xinjiang bordering Russia. Eurasian steppe ancestry identified in Narensu has changed to the late Bronze Age Sintashta populations, and eastern Eurasian ancestry from Baikal turns prominent since the Iron Age. Conclusions Here, by reconstructing the population dynamics from the Chalcolithic to the Iron Age, our study reveals that the Narensu inhabitants have continuously accumulated with multiple waves of gene influx from surrounding regions. Altogether, these findings provide a comprehensive picture into the population fusion history of northwestern Xinjiang as well as across the Eurasian continent.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries. Hepatitis B virus is an ancient human pathogen that dates back more than 10,000 years. Here, the authors investigate the evolutionary history of the virus in Eastern Eurasia by sequencing 34 genomes dating from approximately 400–5,000 years ago and comparing them with other contemporary sequences.

Salmonella enterica ( S . enterica ) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S . enterica . We reconstructed S . enterica genomes from those individuals, which form a previously undetected phylogenetic branch basal to Paratyphi C, Typhisuis and Choleraesuis–the so-called Para C lineage. Based on pseudogene frequency, our analysis suggests that the ancient S . enterica strains were not host adapted. One genome, however, harbors the Salmonella pathogenicity island 7 (SPI-7), which is thought to be involved in (para)typhoid disease in humans. This offers first evidence that SPI-7 was acquired prior to the emergence of human-adapted Paratyphi C around 1,000 years ago. Altogether, our results show that Salmonella enterica infected humans in Eastern Eurasia at least 3,000 years ago, and provide the first ancient DNA evidence for the spread of a pathogen along the Proto-Silk Road.

In order to study the genetic characteristics of the Lower Xiajiadian culture (LXC) population, a main bronze culture branch in northern China dated 4500–3500 years ago, two uniparentally inherited markers, mitochondrial DNA and Y-chromosome single-nucleotide polymorphisms (Y-SNPs), were analyzed on 14 human remains excavated from the Dadianzi site. The 14 sequences, which contained 13 haplotypes, were assigned to 9 haplogroups, and Y-SNP typing of 5 male individuals assigned them to haplogroups N (M231) and O3 (M122). The results indicate that the LXC population mainly included people carrying haplogroups from northern Asia who had lived in this region since the Neolithic period, as well as genetic evidence of immigration from the Central Plain. Later in the Bronze Age, part of the population migrated to the south away from a cooler climate, which ultimately influenced the gene pool in the Central Plain. Thus, climate change is an important factor, which drove the population migration during the Bronze Age in northern China. Based on these results, the local genetic continuity did not seem to be affected by outward migration, although more data are needed especially from other ancient populations to determine the influence of return migration on genetic continuity.

Dairy and millets have long sustained agropastoral societies in Inner Asia. While dairy pastoralism emerged across the eastern Eurasian steppe from 3000 BCE, the timing and process of its introduction into the Inner Asian mountains and integration with millet agriculture remains unclear due to the gaps in archaeological record. Here we present a long-term record of dairy–millet integration in the Inner Asian mountains, based on chronological, palaeoproteomic, and stable isotope analyses of the Narensu cemetery (3050 BCE–1430 CE) in Xinjiang. This evidence reveals the earliest known convergence of Eastern–Western agropastoral technologies from 2900 BCE. Horse milk was widely consumed by 840 BCE, followed by an intensification of agrarian product consumption during the Han–Xiongnu period. Combined with cross-regional evidence, we argue that the synergy of dairy pastoralism and millet shaped a sustainable mixed economy, underpinning resilient subsistence strategies and long-term socio-ecological adaptation in Xinjiang’s diverse environments. Dairy pastoralism and millet agriculture formed a mixed agropastoral economy in the Inner Asian mountains from as early as 2900 BCE, enabling subsistence and socio-ecological adaptation in Xinjiang, based on chronological, palaeoproteomic, and stable-isotope analyses of the Narensu cemetery.

To gain a better understanding of North American population history, complete mitochondrial genomes (mitogenomes) were generated from four ancient and three living individuals of the northern Northwest Coast of North America, specifically the north coast of British Columbia, Canada, current home to the indigenous Tsimshian, Haida, and Nisga'a. The mitogenomes of all individuals were previously unknown and assigned to new sub-haplogroup designations D4h3a7, A2ag and A2ah. The analysis of mitogenomes allows for more detailed analyses of presumed ancestor-descendant relationships than sequencing only the HVSI region of the mitochondrial genome, a more traditional approach in local population studies. The results of this study provide contrasting examples of the evolution of Native American mitogenomes. Those belonging to sub-haplogroups A2ag and A2ah exhibit temporal continuity in this region for 5000 years up until the present day. Of possible associative significance is that archaeologically identified house structures in this region maintain similar characteristics for this same period of time, demonstrating cultural continuity in residence patterns. The individual dated to 6000 years before present (BP) exhibited a mitogenome belonging to sub-haplogroup D4h3a. This sub-haplogroup was earlier identified in the same general area at 10300 years BP on Prince of Wales Island, Alaska, and may have gone extinct, as it has not been observed in any living individuals of the Northwest Coast. The presented case studies demonstrate the different evolutionary paths of mitogenomes over time on the Northwest Coast.

Background The Tarim Basin, located on the ancient Silk Road, played a very important role in the history of human migration and cultural communications between the West and the East. However, both the exact period at which the relevant events occurred and the origins of the people in the area remain very obscure. In this paper, we present data from the analyses of both Y chromosomal and mitochondrial DNA (mtDNA) derived from human remains excavated from the Xiaohe cemetery, the oldest archeological site with human remains discovered in the Tarim Basin thus far. Results Mitochondrial DNA analysis showed that the Xiaohe people carried both the East Eurasian haplogroup (C) and the West Eurasian haplogroups (H and K), whereas Y chromosomal DNA analysis revealed only the West Eurasian haplogroup R1a1a in the male individuals. Conclusion Our results demonstrated that the Xiaohe people were an admixture from populations originating from both the West and the East, implying that the Tarim Basin had been occupied by an admixed population since the early Bronze Age. To our knowledge, this is the earliest genetic evidence of an admixed population settled in the Tarim Basin.