Journal of Genetics and Genomics最新文献

Yunnan Province has long served as a key nexus facilitating economic and cultural exchanges between East Asia, Southeast Asia, and Qinghai-Tibet Plateau. However, previous genetic studies were largely limited by sparse marker density, low sequencing depth, or single-population designs, leaving the population genetic structure and demographic history insufficiently resolved. Here, we conduct a high-resolution population genetic study based on 366 high-depth whole-genome sequencing samples from six ethnic groups, including Bai, Dai, Hani, Miao, Tibetan, and Han. We identify approximately 3.51 million novel variants and reveal fine-scale population structure and complex demographic histories among Yunnan ethnic groups. Beyond the three ancestries proposed by the tri-genealogy hypothesis, we detect a Han Chinese-related lineage, Yan-Huang, within multiple Yunnan populations. We further demonstrate that Yunnan represents a major gene-flow hotspot across East and Southeast Asia despite geographic barriers. Finally, we identify genomic loci under positive selection with candidate genes enriched in immune regulation, energy metabolism, cardiac development, and dietary adaptation, highlighting the role of local environmental pressures in shaping the genetic diversity of Yunnan populations.

The 13th-century Changzhou Mummy, from the Lower Yangtze region in China, is the earliest known East Asian case of an artificially mummified body employing mercury and cinnabar enema without evisceration. This study conducts multidisciplinary research, integrating paleo-radiological, paleo-pathological, paleo-genetic, and paleo-nutritional analysis to investigate the phenotype, genotype, individual life history, and the process of deliberate mummification performed on this individual. We generate a whole genome with 12.7× coverage, revealing potential genetic predisposition for several atherosclerotic cardiovascular diseases (ASCVD). Stable C and N isotope analysis of bones, teeth and hairs indicates high animal protein consumption as well as terminal illness. Hereditary and dietary risk factors are consistent with the diagnosis of atherosclerosis determined via postmortem examination. Our study, leveraging high-quality ancient DNA, provides a unique opportunity to challenge and rethink the widely accepted consensus on the relationship between atherosclerosis and post-industrial age lifestyles, uncovering unrecognized genetic polymorphisms of ASCVD among ancient individuals, and improving our understanding of the role of genetic factors in the development and evolution of ASCVD.

Mammalian oocyte maturation relies on the precise assembly of the acentrosomal spindle, and its disruption causes aneuploidy and developmental failure. Symplekin (SYMPK), a 3'-end processing scaffold with emerging functions in regulating chromosome dynamics, remains unexplored in oocytes. Here, we investigate whether SYMPK governs spindle dynamics and chromosome fidelity during meiotic maturation. We find SYMPK dynamically tracks spindle microtubules during oocyte maturation following germinal vesicle breakdown (GVBD). By generating oocyte-specific Sympk knockout mice, loss of SYMPK in oocytes yields complete female infertility and impaired oocyte quality. Sympk-deficient oocytes show a predominant metaphase I (MI) arrest, accompanied by disorganized spindle architecture and destabilized kinetochore-microtubule attachments. Furthermore, chromosome spreads indicate persistent spindle assembly checkpoint (SAC) activation, and pharmacologic SAC inhibition can partially restore meiotic progression but not spindle integrity in SYMPK-deficient oocytes. Mechanistically, immunoprecipitation-mass spectrometry in MI oocytes reveals that SYMPK interacts with the spindle regulators KIF20A and NUMA1, and is required for their proper localization to the spindle. Collectively, these findings establish that SYMPK supports KIF20A and NUMA1 to coordinate acentrosomal spindle organization, thereby safeguarding oocyte meiotic maturation and ensuring faithful female meiotic progression.

Potassium channels regulate diverse biological processes, ranging from cell proliferation to immune responses. However, the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized. Here, we identify Sandman (Sand), a two-pore-domain potassium channel in Drosophilamelanogaster, as an essential regulator for the proliferation of intestinal stem cells and malignant tumors, while dispensable for the normal development processes. Mechanistically, loss of sand elevates intracellular K⁺ concentration, leading to growth inhibition. This phenotype is rescued by pharmacological reduction of intracellular K⁺ levels using the K⁺ ionophore. Conversely, overexpression of sand triggers stem cell death in most regions of the midgut, inhibits tumor growth, and induces a Notch loss-of-function phenotype in the posterior midgut. These effects are mediated predominantly via the induction of endoplasmic reticulum (ER) stress, as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s. Additionally, human homologues of Sand demonstrated similar ER stress-inducing capabilities, suggesting an evolutionarily conserved relationship between this channel and ER stress. Together, our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis, and reveal a link between the two-pore potassium channel and ER stress signaling.

Cell competition is an evolutionarily ancient mechanism that functions to remove unfit or dangerous clonal cells in a multicellular community. A classical model is the removal of polarity-deficient clones, such as the precancerous scribble (scrib) mutant clones, in Drosophila imaginal discs. The activation of Ras, Yki, or Notch signaling robustly reverses the scrib mutant clonal fate from elimination to tumorous growth. Whether these signals converge to adopt a common mechanism to overcome the elimination pressure posed by cell competition remains unclear. Using single-cell transcriptomics, we find that a critical converging point downstream of Ras, Yki, and Notch signals is the upregulation of Upd2, an IL-6 family cytokine. Overexpression of Upd2 is sufficient to rescue the scrib mutant clones from elimination. Depletion of Upd2 blocks the growth of the scrib mutant clones with active Ras, Yki, and Notch signals. Moreover, Upd2 overexpression promotes robust intestinal stem cell (ISC) proliferation, while Upd2 is intrinsically required in ISCs for the growth of the adult intestine. Together, these results identify Upd2 as a crucial cell fitness factor that sustains tissue growth but can potentiate tumorigenesis when deregulated.

Anther is a key male reproductive organ that is essential for the plant life cycle, from the sporophyte to the gametophyte generation. To explore the isoform-level transcriptional landscape of developing anthers in maize (Zea mays L.), we analyzed Iso-Seq data from anthers collected at 10 developmental stages, together with strand-specific RNA-seq, CAGE-seq, and PAS-seq data. Of the 152,026 high-confidence full-length isoforms identified, 68.8% have not been described; these include 22,365 isoforms that originate from previously unannotated loci and 82,167 novel isoforms that originate from annotated protein-coding genes. Using our newly developed strategy to detect dynamic expression patterns of isoforms, we identify 13,899 differentially variable regions (DVRs); surprisingly, 1275 genes contain more than two DVRs, revealing highly efficient utilization of limited genic regions. We identify 7876 long non-coding RNAs (lncRNAs) from 4098 loci, most of which were preferentially expressed during cell differentiation and meiosis. We also detected 371 long-range interactions involving intergenic lncRNAs (lincRNAs); interestingly, 243 were lincRNA-gene ones, and the interacting genes were highly expressed in anthers, suggesting that many potential lncRNA regulators of key genes are required for anther development. This study provides valuable resources and fundamental information for studying the essential transcripts of key genes during anther development.

α-Zeins, the major maize endosperm storage proteins, are transcriptionally regulated by Opaque2 (O2) and prolamin-box-binding factor 1 (PBF1), with Opaque11 (O11) functioning upstream of them. However, whether O11 directly binds to α-zein genes and its regulatory interactions with O2 and PBF1 remain unclear. Using the small-kernel mutant sw1, which exhibits decreased 19-kDa and increased 22-kDa α-zein, we positionally clone O11 and find it directly binds to G-box/E-box motifs. O11 activates 19-kDa α-zein transcription, stronger than PBF1 but weaker than O2. Notably, PBF1 competitively binds to an overlapping E-box/P-box motif, and represses O11-mediated transactivation. Although O11 does not physically interact with O2, it participates in the O2-centered hierarchical network to enhance α-zein expression. sw1 o2 and sw1 pbf1 double mutants exhibit smaller, more opaque kernels with further reduced 19-kDa and 22-kDa α-zeins compared to the single mutants, suggesting distinct regulatory effects of these transcription factors on 19-kDa and 22-kDa α-zein genes. Promoter motif analysis suggests that O11, PBF1, and O2 directly regulate 19-kDa α-zein genes, while O11 indirectly controls 22-kDa α-zein genes via O2 and PBF1 modulation. These findings identify the unique and coordinated roles of O11, O2, and PBF1 in regulating α-zein genes and kernel development.

Marchantia polymorpha, a model liverwort, provides a valuable system for investigating the evolution of plant sexual reproduction. To explore the cellular landscape of its reproductive structures, we generate a single-nucleus transcriptomic atlas of the antheridiophore, archegoniophore, and sporophyte. Using single-nucleus RNA sequencing (snRNA-seq), we capture over 30,000 high-quality nuclei and identify distinct cell populations. In the male organ, we characterize stages of spermatogenesis from early antheridium cells to mature sperm, revealing dynamic transcriptional programs including cell cycle regulation, chromatin remodeling, and calcium signaling. In the female organ, we define cell types including archegonial layers and secondary central cells. Sporophyte clusters are annotated as spores, elaters, capsule wall, foot, and seta cells, with transcriptional signatures related to structural support, stress response, and reproductive functions. Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells. Notably, foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways, serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte. This study provides a comprehensive cellular and molecular map of M. polymorpha reproductive organs and sporophyte, establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.

Hearing and balance disorders are significant health issues primarily caused by developmental defects or the irreversible loss of sensory hair cells (HCs). Identifying the underlying genes involved in the morphogenesis and development of HCs is crucial. Our current study highlights rhpn2, a member of rho-binding proteins, as essential for vestibular HC development. The rhpn2 gene is highly expressed in the crista and macula HCs. Loss of rhpn2 function in zebrafish reduces the otic vesicle area and vestibular HC number, accompanied by vestibular dysfunction. Shorter stereocilia and compromised mechanotransduction channel function are found in the crista HCs of rhpn2 mutants. Transcriptome RNA sequencing analysis predicts the potential interaction of rhpn2 with rhoab. Furthermore, co-immunoprecipitation confirms that Rhpn2 directly binds to RhoA, validating the interaction of the two proteins. rhpn2 knockout leads to a decreased expression of rock2b, a canonical RhoA signaling pathway gene. Treatment with the RhoA activator or exogenous rock2b mRNA injection mitigates crista HC stereocilia defects in rhpn2 mutants. This study uncovers the role of rhpn2 in vestibular HC development and stereocilia formation via mediating the RhoA signaling pathway, providing a target for the treatment of balance disorders.