Biology subjects

Wang, D.

Publications and source records attributed to Wang, D..

At least 361 records · Page 20Linked to original sources

bioRxiv2024

Early evolution of the ecdysozoan body plan

Extant ecdysozoans (moulting animals) are represented by a great variety of vermiform or articulated organisms. However, controversies remain about the nature of their ancestral body plan although the vermiform hypothesis seems to prevail. We describe here Beretella spinosa gen et sp. nov. a tiny ecdysozoan from the early Cambrian, Yanjiahe Formation, South China, with an unusual sack-like appearance, single opening, and spiny ornament. Beretella has no equivalent among animals, except Saccorhytus from the basal Cambrian. Phylogenetic analyses resolve both forms as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early dead-end off-shot along the stem-line Ecdysozoa that possibly evolved through anatomical simplification (e.g. lack of anus). Although extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature (possibly non-vermiform) of the earliest representatives of the group.

paleontology↗

bioRxiv2024

Non-Necroptotic Roles of MLKL in Diet-Induced Obesity, Liver Pathology, and Insulin Sensitivity: Insights from a High Fat, High Fructose, High Cholesterol Diet Mouse Model

Chronic inflammation is a key player in metabolic dysfunction-associated fatty liver disease (MAFLD) progression. Necroptosis, an inflammatory cell death pathway, is elevated in MAFLD patients and mouse models, yet its role is unclear due to diverse mouse models and inhibition strategies. In our study, we inhibited necroptosis by targeting mixed lineage kinase domain like pseudokinase (MLKL), the terminal effector of necroptosis, in a high-fat, high-fructose, high-cholesterol (HFHFrHC) mouse model of diet-induced MAFLD mouse model. Despite HFHFrHC diet upregulating MLKL (2.5-fold), WT mice livers showed no increase in necroptosis markers or associated proinflammatory cytokines. Surprisingly, Mlkl-/-mice experienced exacerbated liver inflammation without protection from diet-induced liver damage, steatosis, or fibrosis. In contrast, Mlkl+/- mice showed significant reduction in these parameters that was associated with elevated Ppar and Ppar{gamma} levels. Both Mlkl-/-and Mlkl+/- mice on HFHFrHC diet resisted diet-induced obesity, attributed to increased beiging, enhanced oxygen consumption and energy expenditure due to adipose tissue, and exhibited improved insulin sensitivity. These findings highlight the tissue specific effects of MLKL on the liver and adipose tissue, and suggest a dose-dependent effect of MLKL on liver pathology.

biochemistry↗

bioRxiv2024

Unraveling wheat endosperm development: epigenetic regulation and novel regulators for enhanced yield and quality

Starch content and seed storage protein (SSP) composition are critical factors influencing wheat grain yield and quality. To uncover the molecular mechanisms governing their biosynthesis, we conducted transcriptome and epigenome profiling across key endosperm developmental stages, revealing that chromatin accessibility, H3K27ac, and H3K27me3 collectively regulate SSP and starch genes with varying impact. Population transcriptome and phenotype analyses highlighted the crucial role of accessible promoter regions as a genetic variation resource, influencing grain yield and quality in a core collection of wheat accessions. By integrating time-serial RNA-seq and ATAC-seq data, we constructed a hierarchical transcriptional regulatory network (TRN) governing starch and SSP biosynthesis, identifying 42 high-confidence novel candidates. These candidates exhibited overlap with genetic regions associated with grain size and quality traits, and their functional significance was validated through expression-phenotype association analysis among wheat accessions and TILLING mutants. In-depth functional analysis of wheat abscisic acid insensitive 3-A1 (TaABI3-A1) with genome editing knock-out lines demonstrated its role in promoting SSP accumulation while repressing starch biosynthesis through transcriptional regulation. An elite haplotype of TaABI3-A1 with higher grain weight was identified during the breeding process in China, and its superior trait was associated with altered TaABI3-A1 expression levels. Additionally, we identified the potential upstream regulator, wheat GAGA-binding transcription factor 1 (TaGBP1), influencing TaABI3-A1 expression. Our study provides novel and high-confidence regulators, presenting an effective strategy for understanding the regulation of SSP and starch biosynthesis and contributing to breeding enhancement.

plant biology↗

bioRxiv2024

Epsins promote atherosclerosis through VSMC phenotypic modulation

Smooth muscle cells in major arteries play a crucial role in regulating coronary artery disease. Conversion of smooth muscle cells into other adverse cell types in the artery propels the pathogenesis of the disease. Curtailing artery plaque buildup by modulating smooth muscle cell reprograming presents us a new opportunity to thwart coronary artery disease. Here, our report how Epsins, a family of endocytic adaptor proteins oversee the smooth muscle cell reprograming by influencing master regulators OCT4 and KLF4. Using single-cell RNA sequencing, we characterized the phenotype of modulated smooth muscle cells in mouse atherosclerotic plaque and found that smooth muscle cells lacking epsins undergo profound reprogramming into not only beneficial myofibroblasts but also endothelial cells for injury repair of diseased endothelium. Our work lays concrete groundwork to explore an uncharted territory as we show that depleting Epsins bolsters smooth muscle cells reprograming to endothelial cells by augmenting OCT4 activity but restrain them from reprograming to harmful foam cells by destabilizing KLF4, a master regulator of adverse reprograming of smooth muscle cells. Moreover, the expression of Epsins in smooth muscle cells positively correlates with the severity of both human and mouse coronary artery disease. Integrating our scRNA- seq data with human Genome-Wide Association Studies (GWAS) identifies pivotal roles Epsins play in smooth muscle cells in the pathological process leading to coronary artery disease. Our findings reveal a previously unexplored direction for smooth muscle cell phenotypic modulation in the development and progression of coronary artery disease and unveil Epsins and their downstream new targets as promising novel therapeutic targets for mitigating metabolic disorders.

cell biology↗

bioRxiv2023

A highly contiguous hexaploid wheat genome assembly facilitates analysis of 1RS translocation and mining of a new adult plant resistance locus to yellow rust disease

High-quality genome information is essential for efficiently deciphering and improving crop traits. Here we report a highly contiguous hexaploid genome assembly for the key wheat breeding parent Zhou8425B, an elite 1BL/1RS translocation line with durable adult plant resistance (APR) against rust diseases. By using HiFi and Hi-C sequencing reads, a 14.75 Gb genome assembly, with contig N50 and scaffold N50 values reaching 70.94 and 735.11 Mb, respectively, was developed. Comparison with 16 previously sequenced common wheat cultivars revealed unique chromosomal structural features in Zhou8425B. Notably, the 1RS translocation in Zhou8425B was apparently longer and carried more genes encoding AP2/ERF-ERF and B3 transcription factors relative to its counterpart in several genome sequenced 1BL/1RS varieties and rye lines. Aided by Zhou8425B genome assembly, a new APR locus (i.e., YrZH3B) against yellow rust (YR) disease was finely mapped to a 1 - 2 Mb interval on chromosome 3BS. Analysis with 212 Zhou8425B derivative varieties showed that pyramiding of YrZH3B with two other APR loci (YrZH22 and YrZH84) significantly decreased YR severity and enhanced grain yield, with triple combination (YrZH3B/YrZH22/YrZH84) having the highest effects. Our data demonstrate the high value of Zhou8425B assembly in studying wheat genome and agronomically important genes.

genomics↗

bioRxiv2023

TaNF-Y-PRC2 orchestrates temporal control of starch and protein synthesis in wheat

The endosperm in cereal grains is instrumental in determining grain yield and seed quality, as it controls the production of starch and protein. In this study, we identified a specific TaNF-Y trimeric complex, consisting of TaNF-YA3-D, TaNF-YB7-B, and TaNF-YC6-B, exhibiting robust expression within endosperm during grain filling stage in wheat. Knock-down of either TaNF-YA3 or TaNF-YC6 led to less starch but more gluten proteins. Detailed analyses have unveiled that the TaNF-Y indirectly boosts starch biosynthesis genes by reducing TaNAC019, a repressor of TaAGPS1a, TaSuS2, thereby regulating starch biosynthesis. Conversely, the TaNF-Y directly inhibits the expression of gliadin and low molecular weight (LMW)-GS coding genes, including TaGli-{gamma}-700 and TaLMW-400. Furthermore, the TaNF-Y components interact with TaSWN, the histone methyltransferase subunit of Polycomb repressive complex 2 (PRC2), to repress the expression of TaNAC019, TaGli-{gamma}-700, and TaLMW-400 through H3K27me3 modification. Notably, weak mutation of TaFIE, core subunit of PRC2, has reduced starch but elevated gliadin and LMW-GS levels. Intriguingly, DNA variations of TaNF-Y components are widely associated with seed developmental traits. In particular, variation within the coding region of TaNF-YB7-B is linked to differences in starch and protein content. Distinct haplotypes of TaNF-YB7-B affect its interaction with TaSWN, influencing the repression of targets like TaNAC019 and TaGli-{gamma}-700. Our findings illuminate the intricate molecular mechanisms governing epigenetic regulation by the TaNF-Y-PRC2 for wheat endosperm development. Manipulating the TaNF-Y complex holds potential for optimizing grain yield and enhancing quality.

plant biology↗

bioRxiv2023

One million years of solitude: the rapid evolution of de novo protein structure and complex

Recent studies have established that de novo genes, evolving from non-coding sequences, enhance protein diversity through a stepwise process. However, the pattern and rate of their structural evolution over time remain unclear. Here, we addressed these issues within a short evolutionary timeframe ([~]1 million years for 97% of rice de novo genes). We found that de novo genes evolve faster than gene duplicates in the intrinsic disordered regions (IDRs, such as random coils), secondary structural elements (such as -helix and {beta}-strand), hydrophobicity, and molecular recognition features (MoRFs). Specifically, we observed an 8-14% decay in random coils and IDR lengths per million years per protein, and a 2.3-6.5% increase in structured elements, hydrophobicity, and MoRFs. These patterns of structural evolution align with changes in amino acid composition over time. We also revealed significantly higher positive charges but smaller molecular weights for de novo proteins than duplicates. Tertiary structure predictions demonstrated that most de novo proteins, though not typically well-folded on their own, readily form low-energy and compact complexes with extensive residue contacts and conformational flexibility, suggesting "a faster-binding" scenario in de novo proteins to promote interaction. Our findings illuminate the rapid evolution of protein structure in the early life of de novo proteins in rice genome, originating from noncoding sequences, highlighting their quick transformation into active, complex-forming components within a remarkably short evolutionary timeframe.

evolutionary biology↗

bioRxiv2023

CD4+ T cells are homeostatic regulators during Mtb reinfection

Immunological priming - either in the context of prior infection or vaccination - elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Here, using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrate that prior Mtb infection elicits a long-lasting protective response against subsequent Mtb exposure and that the depletion of CD4+ T cells prior to Mtb rechallenge significantly abrogates this protection. Leveraging microbiologic, PET-CT, flow cytometric, and single-cell RNA-seq data from primary infection, reinfection, and reinfection-CD4+ T cell depleted granulomas, we identify differential cellular and microbial features of control. The data collectively demonstrate that the presence of CD4+ T cells in the setting of reinfection results in a reduced inflammatory lung milieu characterized by reprogrammed CD8+ T cell activity, reduced neutrophilia, and blunted type-1 immune signaling among myeloid cells, mitigating Mtb disease severity. These results open avenues for developing vaccines and therapeutics that not only target CD4+ and CD8+ T cells, but also modulate innate immune cells to limit Mtb disease.

immunology↗

bioRxiv2023

The somato-cognitive action network links diverse neuromodulatory targets for Parkinson's disease

The newly-recognized somato-cognitive action network (SCAN) is posited to be important in movement coordination. Functional disruptions in Parkinsons disease (PD) correspond with complex, non-effector-specific motor symptoms, indicating that SCAN dysfunction may underlie these symptoms. Along the same lines, the SCAN may link multiple neuromodulatory targets used for PD treatment. To investigate the role of the SCAN in PD, we leveraged resting-state precision functional mapping, analyzing data from 673 individuals across 6 independent datasets and 5 types of neuromodulation. Our findings revealed functional abnormalities within the SCAN in PD patients and the selective involvement of the SCAN in diverse neuromodulatory targets. Moreover, our data suggests causal links between SCAN connectivity changes and motor symptom alleviation following both invasive and non-invasive neuromodulation. Collectively, these findings underscore the critical role of the SCAN in the pathophysiology of PD and its brain stimulation treatments, and suggest the SCAN as a promising candidate target for neuromodulation.

neuroscience↗

bioRxiv2023

Molecular Determinants and Signaling Effects of PKA RIα Phase Separation

Spatiotemporal regulation of intracellular signaling molecules, such as the 3,5-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures the specific execution of various cellular functions. Liquid-liquid phase separation (LLPS) of the ubiquitously expressed PKA regulatory subunit RI was recently identified as a major driver of cAMP compartmentation and signaling specificity. However, the molecular determinants of RI LLPS remain unclear. Here, we reveal that two separate dimerization interfaces combined with the cAMP-induced release of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence are required to drive RI condensate formation in cytosol, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RI pseudosubstrate region is critically involved in the formation of a non-canonical R:C complex, which serves to maintain low basal PKA activity in the cytosol by enabling the recruitment of active PKA-C to RI condensates. Our results suggest that RI LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity.

cell biology↗

bioRxiv2023

Toward Best Practice in Identifying Subtle Differential Expression with RNA-seq: A Real-World Multi-Center Benchmarking Study Using Quartet and MAQC Reference Materials

Translating RNA-seq into clinical diagnostics requires ensuring the reliability of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. Moreover, cross-laboratory reproducibility and consistency under diverse experimental and bioinformatics workflows urgently need to be addressed. As part of the Quartet project, we presented a comprehensive RNA-seq benchmarking study utilizing Quartet and MAQC RNA reference samples spiked with ERCC controls in 45 independent laboratories, each employing their in-house RNA-seq workflows. We assessed the data quality, accuracy and reproducibility of gene expression and differential gene expression and compared over 40 experimental processes and 140 combined differential analysis pipelines based on multiple ground truths. Here we show that real-world RNA-seq exhibited greater inter-laboratory variations when detecting subtle differential expressions between Quartet samples. Experimental factors including mRNA enrichment methods and strandedness, and each bioinformatics step, particularly normalization, emerged as primary sources of variations in gene expression and have a more pronounced impact on the subtle differential expression measurement. We underscored the pivotal role of experimental execution over the choice of experimental protocols, the importance of strategies for filtering low-expression genes, and optimal gene annotation and analysis tools. In summary, this study provided best practice recommendations for the development, optimization, and quality control of RNA-seq for clinical diagnostic purposes.

genomics↗

bioRxiv2023

Movement-related increases in subthalamic activity optimize locomotion

The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation typically has opposing effects. Subthalamic and motor activity are also inversely correlated in movement disorders. However, most STN neurons exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and -paced treadmill locomotion. The majority of STN neurons (type 1) exhibited locomotion-dependent increases in activity, with half encoding the locomotor cycle. A minority of neurons exhibited dips in activity or were uncorrelated with movement. Brief optogenetic inhibition of the dorsolateral STN (where type 1 neurons are concentrated) slowed and prematurely terminated locomotion. In Q175 Huntingtons disease mice abnormally brief, low-velocity locomotion was specifically associated with type 1 hypoactivity. Together these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.

neuroscience↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Targeting endothelial FOXO1 protects diabetic β-cells and improves wound healing

The forkhead box O1 (FOXO1) transcription factor plays critical roles in regulating not only metabolic activity but also angiogenesis in the vascular endothelium1-4. Our previous studies show that epsin endocytic adaptors can regulate both angiogenesis and lymphangiogenesis5-7. Endothelial cells (ECs) lining the inside of blood vessels are continuously exposed to circulating insulin and insulin-like growth factors (IGFs). Emerging evidences suggest that ECs can affect {beta}-cell function8-11. Excessive IGF2, especially elevated local IGF2 levels in islets, may represent a risk factor for developing diabetes12-15; however, the underlying molecular mechanisms by which aberrant angiogenesis and endothelium-derived factors regulate pancreatic {beta}-cell function in diabetes remain unclear. Here, we report that the pancreas of diabetic patients as well as the pancreas, skin, and plasma of streptozotocin/high fat diet (STZ/HFD)-induced diabetic mice and db/db mice contains excess IGF2, which can lead to {beta}-cell dysfunction and apoptosis. Single-cell transcriptomics combined with mass spectrometry analysis reveal that endothelial-specific knockout of FOXO1 increases circulating soluble and cell-membrane or intracellular expression levels of IGF type 2 receptor (IGF2R) and CCCTC-binding factor (CTCF), while decreasing IGF2 levels in diabetes. Both IGFR215-17 and CTCF18-21 can reduce IGF2 levels and may ameliorate {beta}-cell decline associated with excess IGF2 in diabetes. Furthermore, depletion of FOXO1, epsins, or knockdown of ULK1 inhibits autophagy formation in ECs, preventing degradation of vascular endothelial growth factor receptor 2 (VEGFR2) to promote angiogenesis and improve wound healing in diabetes. Our findings reveal that endothelial FOXO1 regulates epsin-dependent angiogenesis and affects {beta}-cell function and fate through CTCF and IGF2-IGF2R, providing a potential strategy for ameliorating diabetes and accelerating cutaneous wound healing.

cell biology↗

bioRxiv2023

Enhanced surface accessibility of SARS-CoV-2 Omicron spike protein due to an altered glycosylation profile

SARS-CoV-2 spike (S) proteins undergo extensive glycosylation, aiding proper folding, enhancing stability, and evading host immune surveillance. In this study, we used mass spectrometric analysis to elucidate the N-glycosylation characteristics and disulfide bonding of recombinant spike proteins derived from the SARS-CoV-2 Omicron variant (B.1.1.529) in comparison with the D614G spike variant. Furthermore, we conducted microsecond-long molecular dynamics simulations on spike proteins to resolve how the different N-glycans impact spike conformational sampling in the two variants. Our findings reveal that the Omicron spike protein maintains an overall resemblance to the D614G spike variant in terms of site-specific glycan processing and disulfide bond formation. Nonetheless, alterations in glycans were observed at certain N-glycosylation sites. These changes, in synergy with mutations within the Omicron spike protein, result in increased surface accessibility of the macromolecule, including ectodomain, receptor-binding domain, and N-terminal domain. These insights contribute to our understanding of the interplay between structure and function, thereby advancing effective vaccination and therapeutic strategies. TeaserThrough mass spectrometry and molecular dynamics simulations, SARS-CoV-2 Omicron spike is found to be less covered by glycans when compared to the D614G spike variant.

molecular biology↗

bioRxiv2023

Unveiling unique microbial nitrogen cycling and novel nitrification drivers in coastal Antarctica

Although microbial nitrogen (N) cycling plays a pivotal role in Antarctic ecosystems, its underlying mechanisms are largely uncharted. In this study, we unravel the biological origin of nitrate via triple oxygen isotopic composition analysis and systematically profile functional N-cycling genes within soil and lake sediment samples from the ice-free areas of East Antarctica. We successfully reconstruct 1,968 metagenome-assembled genomes (MAGs) spanning 29 microbial phyla, enabling the analysis of the presence or absence of 52 diverse metabolic marker genes. Consistent with quantitative data, our metagenomic analyses confirm the active processes of microbial nitrogen fixation, nitrification, and denitrification. We find no detectable anaerobic ammonium oxidation (anammox) processes, underscoring a unique microbial N-cycling dynamic in the region. Notably, we identify the predominance of complete ammonia-oxidizing (comammox) Nitrospira, a recently discovered bacterial guild capable of performing the entire nitrification process within a single organism. Further genomic investigations reveal their adaptive strategies in the Antarctic environment. These strategies likely involve the synthesis of trehalose to counteract cold stress, high substrate affinity to efficiently utilize available resources, and alternative metabolic pathways to adapt to nutrient-scarce conditions. Their significant role in the nitrification process is validated through 13C-DNA-based stable isotope probing (DNA-SIP). This research provides a comprehensive illustration of nitrifications crucial contribution to the nitrogen budget in coastal Antarctica, highlighting comammox Nitrospira clade B as a novel nitrifying agent and shedding new light on the complex biogeochemical processes of nitrogen cycling in coastal Antarctica.

microbiology↗

bioRxiv2023

USP7 Inhibition Promotes Mesenchymal Stem cell-Macrophage Crosstalk in Age-related Osteoporosis via Efferocytosis and Senolysis

Although elderly osteoporotic patients have similar implant survival rates compared to those of normal individuals, they require longer healing periods to achieve proper osseointegration. This may be related to chronic inflammatory responses and impaired stem cell repair functions in the osteoporotic bone microenvironment. Recently, the deubiquitinating enzyme, ubiquitin-specific peptidase 7 (USP7), was found to regulate macrophage immune response and modulate stem cell osteogenic differentiation. The selective inhibitor of USP7, P5091, has also been found to promote bone repair and homeostasis in osteoporotic conditions. However, the roles of USP7 and P5091 in osteoimmunology and dental implant osseointegration under senile osteoporotic conditions remain unclear. In this study, USP7 depletion and P5091 were showed to inhibit inflammation in senescent bone marrow derived macrophages (BMDMs) and promote osteogenic differentiation in aged BMSCs. Furthermore, mRNA-Seq revealed that USP7 depletion could enhance efferocytosis in senescent BMDMs through the EPSIN1/ low-density lipoprotein receptor-related protein 1 (LRP1) pathway and selectively induce apoptosis (senolysis) in aged BMSCs. In senile osteoporotic mice, we found that the osseointegration period was prolonged compared to young mice, and P5091 promoted the early stage of osseointegration, which may be related to macrophage efferocytosis around the implant. Collectively, this study suggests that USP7 inhibition may accelerate the osseointegration process in senile osteoporotic conditions by promoting macrophage efferocytosis and aged BMSCs apoptosis. This has implications for understanding the cellular interactions and signaling mechanisms in the peri-implant bone microenvironment under osteoporotic conditions. It may also provide clinical significance in developing new therapies to enhance osseointegration quality and shorten the edentulous period in elderly osteoporotic patients.

cell biology↗

bioRxiv2023

Sex chromosome turnover in hybridizing stickleback lineages

Recent discoveries of sex chromosome diversity across the tree of life have challenged the canonical model of conserved sex chromosome evolution and evoked new theories on labile sex chromosomes that maintain less differentiation and undergo frequent turnover. However, theories of labile sex chromosome evolution lack direct empirical support due to the paucity of case studies demonstrating ongoing sex chromosome turnover in nature. Two divergent lineages (viz. WL & EL) of nine-spined sticklebacks (Pungitius pungitius) with different sex chromosomes (linkage group [LG] 12 in the EL, unknown in the WL) hybridize in a natural secondary contact zone in the Baltic Sea, providing an opportunity to study ongoing turnover between coexisting sex chromosomes. We first identified an 80 kbp genomic region on LG3 as the sex-determining region (SDR) using whole-genome resequencing data of family crosses. We then verified this region as the SDR in most other WL populations and demonstrated an ongoing sex chromosome turnover in admixed marine populations where the evolutionarily younger and homomorphic LG3 sex chromosomes replace the older and heteromorphic LG12 sex chromosomes. The results provide a rare glimpse of ongoing sex chromosome turnover and indicate possible existence of additional but yet undiscovered sex chromosome diversity in Pungitius sticklebacks. TeaserEvolutionarily young sex chromosomes replace the older ones in the hybrid zone of European Pungitius stickleback lineages.

evolutionary biology↗