Li Yu

The gliding patagium represents a key adaptation for mammalian flight, but its cellular development remains unexplored. Using single-nucleus RNA sequencing of embryonic flying squirrel patagium and dorsal skin, we construct a single-cell atlas of patagium development and identify two distinct fibroblast subpopulations (Fp2 and Fr) highly enriched in the patagium. These fibroblasts are characterized by the patagium upregulation of Wnt5a, Fgf7, and Fgf10, and are associated with patagium morphogenesis through dermal-epidermal putative communication interactions between dermal fibroblasts (Fp2 and Fr) and epithelial basal keratinocytes. Specifically, Fp2 fibroblasts are potentially involved in distal dermal condensation and epithelial thickening together with elevated Wnt5a expression, while both Fp2 and Fr fibroblasts could play a role in epithelial polarization and thickening through Fgf7 and Fgf10, as suggested by ex vivo assays. Our data suggest that gliding patagium development results from the co-option of conserved WNT and FGF signaling pathways within a specialized fibroblast-epithelial context, illustrating how modifications of conserved developmental programs give rise to derived morphological traits.

The endangered black-and-white snub-nosed monkey (Rhinopithecus bieti), endemic to high-altitude forests in southwest China, has increased from fewer than 1,500 individuals pre-1990 to over 3,500 post-2010. However, it faces severe habitat fragmentation, with at least 20 isolated groups. A comprehensive investigation of large-scale population genomic analysis is lacking. We present the first comprehensive genomic reassessment of this species using fecal-DNA and targeted capture sequencing to generate genome-wide single-nucleotide polymorphism data for 309 individuals. We identified five distinct genetic populations (Southwest, Southeast, Central, North-Central, and North) with strong geographic associations. Furthermore, we found previously unrecognized subpopulations, primarily associated with isolation within human-altered landscapes. Roads and human settlements were the primary barriers to contemporary genetic connectivity. Genetic diversity is highest centrally and declines peripherally, reflecting historical/recent barriers. Demographic inference suggests: (i) a possible southwestern origin and northward dispersal at ∼128.5 to 8.2 ka, probably driven by late Pleistocene climatic oscillations and local refugia; (ii) major subpopulation divergences within the last ∼610 to 120 years ago, likely due to human exploitation; and (iii) a sharp decline ∼300 years ago, leaving extremely low effective population size (40 to 314). Admixture origins of both Southeast and North-Central populations highlight their role in facilitating gene flow. Historically, habitats with high connectivity contrast with current severe fragmentation, particularly in the southern regions; this persistent suitability disparity suggests limited historical connectivity promoting genetic divergence between southern and central/northern populations. Our results provide critical insights into the population structure and evolutionary history of R. bieti, offering critical insights for conservation and demonstrating the power of fecal genomics in endangered species.

Human-driven biodiversity loss, intensified by illegal hunting and trafficking, has caused severe wildlife population declines and extinctions, necessitating studies on long-term genomic erosion to inform conservation strategies. While temporal genomic analyses using ancient and historical/museum DNA reveal generational impacts, sparse sampling often limits insights into prolonged declines, highlighting the need for time-resolved studies to understand sequential population decline and species persistence under sustained pressures. The Chinese pangolin (Manis pentadactyla), critically endangered as a result of historical overexploitation, has experienced severe continuous population decline pre-1979, 1980–1999, and post-2000. However, the temporal genetic consequences and associated extinction risks remain poorly understood. We analyzed 228 pangolin genomes (133 newly sequenced), spanning continuous population decline, to assess the dynamics of genomic erosion. Our results demonstrate that persistent population decline drives long-term genetic decline within populations, with the severity of population decline correlating directly with the degree of negative genetic impact (e.g. reduced diversity, increased inbreeding and genetic load) and extinction risk. Counterintuitively, however, between populations, those experiencing the most severe population decline (e.g. southwest China) exhibited less extreme relative genetic consequences compared to less severe population decline (e.g. south China), suggesting a stronger dependence on the history of effective population size before population decline. Critically, the contemporary South China population shows significantly lower genetic diversity, higher inbreeding, elevated genetic load, and consequently higher extinction risk, demanding urgent prioritization for conservation. This study provides novel insights into the complex genomic legacy of continuous population decline, elucidating anthropogenic impacts on genetic erosion and offering a scientific framework for targeted conservation strategies.

Climate change and human activities since the late Pleistocene have profoundly impacted endemic species on the Qinghai-Tibetan Plateau. The Tibetan antelope (Pantholops hodgsonii), a keystone ungulate once heavily poached, experienced unclear demographic fluctuations in response to these pressures. Using whole-genome resequencing, we analyzed 85 Tibetan antelope individuals across three geographic populations to reconstruct their demographic history. Our findings reveal a climate-driven decline during the Last Glacial Period, with a bottleneck during the Last Glacial Maximum (LGM) and post-LGM recovery, aligning with ecological niche modeling that shows habitat contraction and expansion. We further detected repeated human-induced demographic collapses and recovery dynamics in Tibetan antelopes: (i) Neolithic collapse (around 6–4 thousand years ago) probably due to prehistoric overhunting; (ii) Bronze Age expansion (around 2.4 thousand years ago) possibly due to reduced hunting pressure as humans shifted to agro-pastoralism; (iii) an early 15th century expansion potentially from the influence of Tibetan Buddhism on reducing exploitation; (iv) a brief yet severe recent bottleneck during the 1950s–1990s caused by illegal poaching; and (v) a post-bottleneck recovery since 2000 due to enhanced protection. This study clarifies the interplay between climatic and anthropogenic impacts on Tibetan antelopes, offering insights for conserving the biodiversity on the Qinghai-Tibetan Plateau.

The white-bellied pangolin (Phataginus tricuspis) serves as a critical biogeographic indicator for understanding faunal diversification in African rainforests and is a priority for conservation due to its status as the most heavily trafficked and endangered mammal. However, the species’ evolutionary history and the genetic consequences of population decline remain unclear. In this study, we conducted comprehensive phylogeographic and conservation genomic studies of 209 whole-genomes, including 100 newly sequenced genomes, and 215 mitogenomes covering all geographic ranges. Our findings reveal four whole-genome genetic lineages and six mitochondrial genetic lineages, uncovering mito-nuclear discordance driven by deep mitochondrial divergence and the replacement of some mitochondrial lineages by nuclear lineages. We suggest that Pleistocene refugia and river barriers are hypothesized to have contributed to the pattern of genetic differentiation and biogeographic diversification. Demographic history reconstruction indicates that, historically, the population size dynamics were likely correlated with glacial-interglacial cycles. However, the recent sharp decline in population size can be attributed to overexploitation driven by international trade. The genetic consequence analyses and evolutionary potential simulation reveal that the Nigeria and West Africa lineages exhibit lower levels of genetic diversity, higher levels of inbreeding and genetic load, and lower survival status and future evolutionary potential, than the other lineages, indicating the need for urgent attention and priority conservation action. Our results provide novel insights into the evolutionary history and conservation priorities for white-bellied pangolins and offer a valuable phylogeographic and conservation framework for guiding conservation efforts to safeguard African rainforest biodiversity.

Archipelagos and oceanic islands have remarkably high levels of endemism, which is associated with rapid speciation. The Malayan pangolin (Manis javanica), one of critically endangered Asia pangolin species, occurs in southern Yunnan, China, and on oceanic islands via the Malay peninsula. The question of whether the distribution of Malayan pangolins between the mainland and nearby marine islands has led to deep population differentiation is not well addressed. In-depth investigation of population structure and genetic consequences is of vital importance for protection and conservation of Malayan pangolins. Here we carried out a large-scale population genomic analysis for Malayan pangolins, which revealed three highly distinct genetic populations. The largest population was found to be distributed over a wide area extending from mainland China to almost the whole of South East Asia. The other two smaller populations reported in this study were inferred from Borneo. In addition, based on multiple lines of genomic and skull morphological evidences, we confirmed the existence of a fifth Asian pangolin species (M. mysteria). Genetic diversity and genome-wide inbreeding were at moderate levels, indicating that anthropogenic factors did not significantly weaken the basis of genetic sustainability for Malayan pangolins. However, Malayan pangolins from northeastern Borneo exhibited low genetic diversity, high levels of inbreeding and mutational load, thereby necessitating attention to their protection.

The mammalian species on the Tibetan Plateau are diverse and abundant, yet our understanding of their gut microbiome and antibiotic resistome remains limited. Here, we used metagenomics to analyse the gut microbiota of 2,561 mammals from the Tibetan Plateau, covering 14 species across six orders. Using de novo metagenome assembly, we reconstructed a total of 112,313 high- to medium-quality metagenomic assembly genomes (MAGs), representing 21,902 microbial species, 86% of which were unclassified. More than 8,000 nonredundant antibiotic resistance genes (ARGs) encompassing 28 types were identified in the gut microbiome of Tibetan Plateau mammals. We further conducted a risk assessment of these ARGs, identifying 334 nonredundant ARGs with high-risk characteristics related to human health. Importantly, seven cross-species horizontal gene transfer events involving high-risk ARGs were identified, three of which occurred between human and nonhuman mammalian gut microbiota. Additionally, we found that the abundance of ARGs in human gut microbiomes on the Tibetan Plateau was greater than that in those from eastern China, Europe, and the United States, whereas the abundance of ARGs in livestock gut microbiomes from the Tibetan Plateau was lower than that in livestock gut microbiomes from those regions. This study reveals that the gut microbiota of Tibetan Plateau mammals is a largely unexplored resource and a significant reservoir of ARGs, offering crucial insights into microbiome research and demonstrating potential public health implications.

Island species/populations are characterized by evolutionary uniqueness and a high degree of endemism and extinction. The conservation and restoration of island species/populations have become the most challenging and urgent issues in biodiversity conservation. Chinese pangolin in Taiwan island (Manis pentadactyla pentadactyla) is a well-known, critically endangered, and island-endemic Chinese pangolin subspecies, which has been the focus of conservation concern. Here, we first generated large-scale population genomics data for the Chinese pangolin in Taiwan to address its population structure, demographic history, the genomic consequences of population declines, and survival potential. We revealed that the Chinese pangolin in Taiwan originated in southeast China and was differentiated into Northern and non-Northern populations due to the isolation of the Xueshan and Central Mountain Ranges, proposing to treat them as separate conservation units. The southeast of Taiwan island acted as a refuge for this Chinese pangolin subspecies during the Last Glacial Maximum. The Northern population had experienced a more severe bottleneck and isolation than the non-Northern population, which corresponded to the estimated current lower genetic diversity, higher inbreeding, and genetic load of the Northern population. The modeling results revealed that the Northern population is more seriously affected by climate change than the non-Northern population, which highlights that climate change poses a substantial threat to island biodiversity. The simulation results indicate that the Northern population needs a higher population growth rate to achieve evolutionary potential equal to the non-Northern population over the next 100 years, deserving conservation prioritization. This study enhances the understanding of genetic background, conservation status, and future prospects for Chinese pangolin in Taiwan, as well as the genetic consequences of a small and isolated island population.