Journal of Genetics and Genomics最新文献

Hu sheep is an indigenous breed from the Taihu Lake Plain in China, known for its high fertility. Although Hu sheep belong to the Mongolian group, their demographic history and genetic architecture remain inconclusive. Here, we analyze 697 sheep genomes from representatives of Mongolian sheep breeds. Our study suggests that the ancestral Hu sheep first separated from the Mongolian group approximately 3000 years ago. As Hu sheep migrated from the north and flourished in the Taihu Lake Plain around 1000 years ago, they developed a unique genetic foundation and phenotypic characteristics, which are evident in the genomic footprints of selective sweeps and structural variation landscape. Genes associated with reproductive traits (BMPR1B and TDRD10) and horn phenotype (RXFP2) exhibit notable selective sweeps in the genome of Hu sheep. A genome-wide association analysis reveals that structural variations at LOC101110773, MAST2, and ZNF385B may significantly impact polledness, teat number, and early growth in Hu sheep, respectively. Our study offers insights into the evolutionary history of Hu sheep and may serve as a valuable genetic resource to enhance the understanding of complex traits in Hu sheep.

Histone H2B ubiquitination (H2Bub) is positively linked to transcriptional activation, but the genetic programs affected by H2Bub to enhance drought tolerance remain largely unknown. Here, we show that OsbZIP27 interacts directly with OsHUB1/2 to regulate drought tolerance in rice by binding to the promoters of OsHAK1 and OsGLN1 to achieve H2Bub and transcriptional activation. Consistently, mutations in OsbZIP27 reduce transcription of OsHAK1 and OsGLN1, resulting in increased sensitivity to drought stress. Moreover, loss of OsHUB1 and OsHUB2 function causes hypersensitivity to drought stress, whereas OsHUB2 overexpression enhances drought tolerance. Together, our results indicate that OsbZIP27 coordinates with OsHUB1/2 to enhance rice drought tolerance by increasing H2Bub and expression of OsHAK1 and OsGLN1.

On top of genetic information, organisms have evolved complex and sophisticated epigenetic regulation to adjust gene expression in response to developmental and environmental signals. Key epigenetic mechanisms include DNA methylation, histone modifications and variants, chromatin remodeling, and chemical modifications of RNAs. Epigenetic control of environmental responses is particularly important for plants, which are sessile and unable to move away from adverse environments. Besides enabling plants to rapidly respond to environmental stresses, some stress-induced epigenetic changes can be maintained, providing plants with a pre-adapted state to recurring stresses. Understanding these epigenetic mechanisms offers valuable insights for developing crop varieties with enhanced stress tolerance. Here, we focus on abiotic stresses and summarize recent progress in characterizing stress-induced epigenetic changes and their regulatory mechanisms and roles in plant abiotic stress resistance.

Programmed silencing of γ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes, which determine the stage-specific genome architecture in this region. Identification of cis- or trans-acting mutations contributing to the diverse extent of fetal hemoglobin (Hb F) might illustrate the underlying mechanism of γ-β-globin switching. Here, we recruit a cohort of 1142 β-thalassemia patients and dissect the natural variants in the whole β-globin gene cluster through a targeted next-generation sequencing panel. A previously unreported SNP rs7948668, predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes, is identified to be significantly associated with higher levels of Hb F and age at onset. Gene-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34⁺ cells while the extent of elevation is amplified in the context of β-thalassemia mutations, indicating epistasis effects of the SNP in the regulation of Hb F. Finally, we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS, leading to enhanced competitiveness of HBG promoters to locus control regions. This study highlights the significance of common regulatory SNPs and provides potential targets for treating β-hemoglobinopathy.

Pharyngeal cartilage morphogenesis is crucial for the formation of craniofacial structures. Cranial neural crest cells are specified at the neural plate border, migrate to pharyngeal arches, and differentiate into pharyngeal chondrocytes, which subsequently flatten, elongate, and stack like coins during maturation. Although the developmental processes prior to chondrocyte maturation have been extensively studied, their subsequent changes in morphology and organization remain largely elusive. Here, we show that wnt2bb is expressed in the pharyngeal ectoderm adjacent to the chondrogenic precursor cells in zebrafish. Inactivation of Wnt2bb leads to a reduction in nuclear β-catenin, which impairs chondrogenic precursor proliferation and disrupts chondrocyte morphogenesis and organization, eventually causing a severe shrinkage of pharyngeal cartilages. Moreover, the decrease of β-catenin in wnt2bb^-/- mutants is accompanied by the reduction of Yap expression. Reactivation of Yap can restore the proliferation of chondrocyte progenitors as well as the proper size, shape, and stacking of pharyngeal chondrocytes. Our findings suggest that Wnt/β-catenin signaling promotes Yap expression to regulate pharyngeal cartilage formation in zebrafish.

The growth of Caenorhabditis elegans involves multiple molting processes, during which old cuticles are shed and new cuticles are rapidly formed. This process requires the regulated bulk secretion of cuticle components. The transmembrane protein-39 (TMEM-39) mutant exhibits distinct dumpy and ruptured phenotypes characterized by notably thin cuticles. TMEM-39 primarily co-localizes with the coat protein II complex (COPII) in large vesicles rather than small COPII vesicles. These TMEM-39-associated large vesicles (TMEM-39-LVs) form robustly during the molting period and co-localize with various extracellular matrix components, including BLI-1 collagen, BLI-3 dual oxidase, and carboxypeptidases. Through immunoprecipitation using TMEM39A-FLAG and proteomics analysis in human sarcoma cells, we identify TMEM39A-associated proteins, including TMEM131. Knockdown of TMEM131 results in reduced TMEM39A-LV formation and collagen secretion in both C. elegans and human sarcoma cells, indicating a cooperative role between TMEM39A and TMEM131 in the secretion of extracellular components through the formation of large COPII vesicles. Given the conservation of TMEM39A and its associated proteins between C. elegans and humans, TMEM39A-LVs may represent a fundamental machinery for rapid and extensive secretion across metazoans.

Primordial germ cells (PGCs) are the precursors of germline that are specified at the embryonic stage. Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice. Moreover, the specific regulatory machinery remains largely unexplored, mainly due to the inaccessible nature of this complex biological process in humans. Here, we curate and integrate multi-omics data, including 581 RNA-seq, 54 ATAC-seq, 45 ChIP-seq, and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process, presenting an atlas in the human PGC database (hPGCdb). With these uniformly processed data and integrated analyses, we characterize the potential key transcription factors and regulatory networks governing human germ cell fate. We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown. We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development, as well as soma-derived NOTCH2 signaling for germ cell differentiation. Taken together, we have built a database for human PGCs (http://43.131.248.15:6882) and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development, including both intrinsic and extrinsic regulatory programs.

Agricultural pests cause enormous losses in annual agricultural production. Understanding the evolutionary responses and adaptive capacity of agricultural pests under climate change is crucial for establishing sustainable and environmentally friendly agricultural pest management. In this study, we integrate climate modeling and landscape genomics to investigate the distributional dynamics of the cotton bollworm (Helicoverpa armigera) in the adaptation to local environments and resilience to future climate change. Notably, the predicted inhabitable areas with higher suitability for the cotton bollworm could be eight times larger in the coming decades. Climate change is one of the factors driving the dynamics of distribution and population differentiation of the cotton bollworm. Approximately 19,000 years ago, the cotton bollworm expanded from its ancestral African population, followed by gradual occupations of the European, Asian, Oceanian, and American continents. Furthermore, we identify seven subpopulations with high dispersal and adaptability which may have an increased risk of invasion potential. Additionally, a large number of candidate genes and SNPs linked to climatic adaptation were mapped. These findings could inform sustainable pest management strategies in the face of climate change, aiding future pest forecasting and management planning.

The liver performs several vital functions such as metabolism, toxin removal, and glucose storage through the coordination of various cell types. With the recent breakthrough of the single-cell/single-nucleus RNA-seq (sc/snRNA-seq) techniques, there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features. In this study, we build a unified liver cell atlas uniLIVER (http://lifeome.net/database/uniliver) by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets. Moreover, we introduce LiverCT, a novel machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of "variant" cellular states analogy to the sequence variants in genomic analysis. Applying LiverCT on liver cancer datasets, we find that the "deviated" states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma, and the enrichments of tumor cells with the hepatocyte-cholangiocyte "intermediate" states significantly indicate poor prognosis. Besides, we find the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis. This reference atlas mapping framework can also be extended to any other tissues.

Increasing plant density is an effective strategy for enhancing crop yield per unit land area. A key architectural trait for crops adapting to high planting density is smaller leaf angle (LA). Previous studies have demonstrated that LG1, a SQUAMOSA BINDING PROTEIN (SBP) transcription factor, plays a critical role in LA establishment. However, the molecular mechanisms underlying the regulation of LG1 on LA formation remain largely unclear. In this study, we conduct comparative RNA-seq analysis of the preligule band (PLB) region of wild type and lg1 mutant leaves. Gene Ontology (GO) term enrichment analysis reveals enrichment of phytohormone pathways and transcription factors, including three auxin transport genes ZmPIN1a, ZmPIN1b, and ZmPIN1c. Further molecular experiments demonstrate that LG1 could directly bind to the promoter region of these auxin transport genes and activate their transcription. We also show that double and triple mutants of these ZmPINs genes exhibit varying degrees of auricle size reduction and thus decreased LA. In the contrary, overexpression of ZmPIN1a causes larger auricle and LA. Taken together, our findings establish a functional link between LG1 and auxin transport in regulating PLB formation and provide valuable targets for genetic improvement of LA for breeding high-density tolerant maize cultivars.