bioRxiv - Genetics最新文献

Mitochondrial superoxide acts in the intestine to extend longevity 线粒体超氧化物在肠道中发挥作用延长寿命

bioRxiv - Genetics Pub Date : 2024-09-19 DOI: 10.1101/2024.09.13.612915

Thomas Liontis, Megan M Senchuk, Shusen Zhu, Suleima Jacob-Tomas, Ulrich Anglas, Annika Traa, Sonja K Soo, Jeremy M. Van Raamsdonk

{"title":"Mitochondrial superoxide acts in the intestine to extend longevity","authors":"Thomas Liontis, Megan M Senchuk, Shusen Zhu, Suleima Jacob-Tomas, Ulrich Anglas, Annika Traa, Sonja K Soo, Jeremy M. Van Raamsdonk","doi":"10.1101/2024.09.13.612915","DOIUrl":"https://doi.org/10.1101/2024.09.13.612915","url":null,"abstract":"Reactive oxygen species (ROS) are highly reactive oxygen containing molecules that are generated by normal metabolism. While ROS can cause damage to the building blocks that make up cells, these molecules can also act as intracellular signals that promote longevity. The levels of ROS within the cell can be regulated by antioxidant enzymes, such as superoxide dismutase (SOD), which converts superoxide to hydrogen peroxide. Interestingly, our previous work has shown that disruption of the mitochondrial SOD gene sod-2 results in increased lifespan, indicating that elevating levels of mitochondrial superoxide can promote longevity. To explore the molecular mechanisms involved, we determined the tissues in which disruption of sod-2 is necessary for lifespan extension and the tissues in which disruption of sod-2 is sufficient to extend lifespan. We found that tissue-specific restoration of SOD-2 expression in worms lacking SOD-2 could partially revert changes in fertility, embryonic lethality and resistance to stress, but did not inhibit the effects of sod-2 deletion on lifespan. Knocking down sod-2 expression using RNA interference specifically in the intestine, but not other tissues, was sufficient to extend longevity. Intestine-specific knockdown of sod-2 also increased resistance to heat stress and while decreasing resistance to oxidative stress. Combined, these results indicate that disruption of sod-2 in neurons, intestine, germline, or muscle is not required for lifespan extension, but that decreasing sod-2 expression in just the intestine extends lifespan. This work defines the conditions required for elevated mitochondrial superoxide to increase longevity.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues 组织中染色质特征、转录组和蛋白质的多重空间绘图

bioRxiv - Genetics Pub Date : 2024-09-19 DOI: 10.1101/2024.09.13.612892

Pengfei Guo, Liran Mao, Yufan Chen, Chin Nien Lee, Angelysia Cardilla, Mingyao Li, Marek Bartosovic, Yanxiang Deng

{"title":"Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues","authors":"Pengfei Guo, Liran Mao, Yufan Chen, Chin Nien Lee, Angelysia Cardilla, Mingyao Li, Marek Bartosovic, Yanxiang Deng","doi":"10.1101/2024.09.13.612892","DOIUrl":"https://doi.org/10.1101/2024.09.13.612892","url":null,"abstract":"The phenotypic and functional states of a cell are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome, and metabolome. Spatial omics approaches have enabled the capture of information from different molecular layers directly in the tissue context. However, current technologies are limited to map one to two modalities at the same time, providing an incomplete representation of cellular identity. Such data is inadequate to fully understand complex biological systems and their underlying regulatory mechanisms. Here we present spatial-Mux-seq, a multi-modal spatial technology that allows simultaneous profiling of five different modalities, including genome-wide profiles of two histone modifications and open chromatin, whole transcriptome, and a panel of proteins at tissue scale and cellular level in a spatially resolved manner. We applied this technology to generate multi-modal tissue maps in mouse embryos and mouse brains, which discriminated more cell types and states than unimodal data. We investigated the spatiotemporal relationship between histone modifications, chromatin accessibility, gene and protein expression in neuron differentiation revealing the relationship between tissue organization, function, and gene regulatory networks. We were able to identify a radial glia spatial niche and revealed spatially changing gradient of epigenetic signals in this region. Moreover, we revealed previously unappreciated involvement of repressive histone marks in the mouse hippocampus. Collectively, the spatial multi-omics approach heralds a new era for characterizing tissue and cellular heterogeneity that single modality studies alone could not reveal.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AyurPhenoClusters define common molecular roots for rare diseases and uncover ciliary dysfunctions in syndromic conditions AyurPhenoClusters 确定罕见疾病的共同分子根源，发现综合症中的睫状肌功能障碍

bioRxiv - Genetics Pub Date : 2024-09-19 DOI: 10.1101/2024.09.13.612844

Aditi Joshi, Deepika Jangir, Ashish Sharma, Tanay Anand, Hamendra Verma, Manvi Yadav, Nupur Rangani, Pallavi Joshi, Ravi Pratap Singh, Sandeep Kumar, Shipra Girdhar, Rakesh Sharma, Abhimanyu Kumar, Lipika Dey, Mitali Mukerji

{"title":"AyurPhenoClusters define common molecular roots for rare diseases and uncover ciliary dysfunctions in syndromic conditions","authors":"Aditi Joshi, Deepika Jangir, Ashish Sharma, Tanay Anand, Hamendra Verma, Manvi Yadav, Nupur Rangani, Pallavi Joshi, Ravi Pratap Singh, Sandeep Kumar, Shipra Girdhar, Rakesh Sharma, Abhimanyu Kumar, Lipika Dey, Mitali Mukerji","doi":"10.1101/2024.09.13.612844","DOIUrl":"https://doi.org/10.1101/2024.09.13.612844","url":null,"abstract":"Managing rare genetic diseases with organ centric focus presents a challenge in linking genotypes to phenotypic traits. Ayurveda on the other hand, diagnose diseases with multi-system perspective that are assessed by perturbations along three physiological dimensions viz- kinetic (Vata), metabolic (Pitta) and structural (Kapha) each with distinct phenotypic attributes and molecular correlates. This study explores how rare diseases, can be viewed from an Ayurvedic perspective by unifying the medical terminologies from both disciplines through Human Phenotype Ontology (HPO). Domain experts categorized 10,610 HPO terms into phenotypic groups based on Ayurvedic principles of Vata (V), Pitta (P), and Kapha (K) and used the Expectation Maximization (EM) algorithm to cluster and analyze 12,678 diseases. This revealed six distinct clusters collectively called \"AyurPhenoClusters\". 2814 diseases had unique memberships to single clusters showing enrichment for V/P/K phenotypes. Clusterwise functional annotation revealed the top processes as (i) embryogenesis and skeletal system, morphogenesis; (ii) endocrine and ciliary functions (iii) DNA damage response and cell cycle regulation (iv) inflammation and immune response (v) immune, hemopoiesis, telomere aging (vi) Small molecule metabolism and transport. Most noteworthy, K predominant cluster was significantly enriched for ciliary genes (43%) followed by a V predominant cluster (16 %). Our study also suggests that many rare diseases especially in the V cluster could be potential ciliopathies. This first of its kind of study provides an innovative framework that can bridge the gap between Ayurveda and modern medicine for improved mechanistic understanding of the rare diseases and pave the way for improved diagnostic and therapeutic strategies.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Screening and identification of gene expression in large cohorts of clinical lung cancer samples unveils the major involvement of EZH2 and SOX2 筛查和鉴定大型临床肺癌样本中的基因表达，揭示 EZH2 和 SOX2 的主要参与作用

bioRxiv - Genetics Pub Date : 2024-09-18 DOI: 10.1101/2024.09.17.613500

Niharika, Ankan Roy, Ratan Sadhukhan, Samir Kumar Patra

{"title":"Screening and identification of gene expression in large cohorts of clinical lung cancer samples unveils the major involvement of EZH2 and SOX2","authors":"Niharika, Ankan Roy, Ratan Sadhukhan, Samir Kumar Patra","doi":"10.1101/2024.09.17.613500","DOIUrl":"https://doi.org/10.1101/2024.09.17.613500","url":null,"abstract":"Lung adenocarcinoma (LUAD), the primary subtype of Non-Small Cell Lung Cancer (NSCLC), accounts for 80% to 85% of cases. Due to suboptimal screening method, LUAD is often detected in late stage, leading to aggressive progression and poor outcomes. Therefore, early disease prognosis for the LUAD is high priority. In order to identify early detection biomarkers, we conducted a meta-analysis of mRNA expression TCGA and GTEx datasets from LUAD patients. A total of 795 differentially expressed genes (DEGs) were identified by exploring the Network-Analyst tool and utilizing combined effect size methods. DEGs refer to genes whose expression levels are significantly different (either higher or lower) compared to their normal baseline expression levels. KEGG pathway enrichment analysis highlighted the TNF signaling pathway as being prominently associated with these DEGs. Subsequently, using the MCODE and CytoHubba plugins in Cytoscape software, we filtered out the top 10 genes. Among these, SOX2 was the only gene exhibiting higher expression, while the others were downregulated. Consequently, our subsequent research focused on SOX2. Further transcription factor-gene network analysis revealed that enhancer of zeste homolog 2 (EZH2) is a significant partner of SOX2, potentially playing a crucial role in euchromatin-heterochromatin dynamics. Structure of SOX2 protein suggest that it is a non-druggable transcription factor, literature survey suggests the same; hence, we drove our focus to investigate on potential drug(s) targeting EZH2. Molecular docking analyses predicted most probable inhibitors of EZH2. We employed several predictive analysis tools and identified GSK343, as a promising inhibitor of EZH2.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy LncRNA TAAL是糖尿病视网膜病变中Tie1介导的血管功能的调节因子

bioRxiv - Genetics Pub Date : 2024-09-18 DOI: 10.1101/2024.09.13.612383

Gyan Ranjan, Samriddhi Arora, Sarmeela Sharma, Lakshita Sharma, Rahul C Bhoyar, Vigneshwar Senthivel, Vinod Scaria, Subhabrata Chakrabarti, Inderjeet Kaur, Sridhar Sivasubbu, Rajender K Motiani

{"title":"LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy","authors":"Gyan Ranjan, Samriddhi Arora, Sarmeela Sharma, Lakshita Sharma, Rahul C Bhoyar, Vigneshwar Senthivel, Vinod Scaria, Subhabrata Chakrabarti, Inderjeet Kaur, Sridhar Sivasubbu, Rajender K Motiani","doi":"10.1101/2024.09.13.612383","DOIUrl":"https://doi.org/10.1101/2024.09.13.612383","url":null,"abstract":"Diabetic retinopathy (DR), a leading cause of vision impairment and blindness, is characterized by abnormal retinal vascular changes due to chronic hyperglycemia. The Tie-1 signaling pathway, essential for vascular growth and remodeling, has emerged as a key therapeutic target, though its molecular mechanisms and interactome remain largely unclear. Through a protein-centric approach, we identified a novel lncRNA and named it Tie1-associated angiogenic lncRNA (TAAL). TAAL lncRNA regulates endothelial cell migration, proliferation, tube formation, and permeability by modulating ER-calcium homeostasis and cytoskeleton dynamics. In zebrafish, taal modulation led to angiogenic defects, which were rescued by human TAAL orthologue. Our molecular studies further revealed that TAAL negatively regulates Tie1 protein via ubiquitin-mediated degradation. Notably, TAAL expression is upregulated in the blood of DR patients and downregulated in endothelial DR cell models. Overexpression of TAAL restored endothelial permeability and VE-cadherin surface expression. These findings establish TAAL as a novel regulator of Tie1 protein turnover, with potential therapeutic implications for diabetic retinopathy.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic diversity during selective sweeps in non-recombining populations 非重组种群选择性掠夺期间的遗传多样性

bioRxiv - Genetics Pub Date : 2024-09-18 DOI: 10.1101/2024.09.12.612756

Sachin Kaushik, Kavita Jain, Parul Johri

{"title":"Genetic diversity during selective sweeps in non-recombining populations","authors":"Sachin Kaushik, Kavita Jain, Parul Johri","doi":"10.1101/2024.09.12.612756","DOIUrl":"https://doi.org/10.1101/2024.09.12.612756","url":null,"abstract":"Selective sweeps, resulting from the spread of beneficial, neutral, or deleterious mutations through a population, shape patterns of genetic variation at linked neutral sites. While many theoretical, computational, and statistical advances have been made in understanding the genomic signatures of selective sweeps in recombining populations, substantially less is understood in populations with little/no recombination. We present a mathematical framework based on diffusion theory for obtaining the site frequency spectrum (SFS) at linked neutral sites immediately post and during the fixation of moderately or strongly beneficial mutations. We find that when a single hard sweep occurs, the SFS decays as 1/x for low derived allele frequencies (x), similar to the neutral SFS at equilibrium, whereas at higher derived allele frequencies, it follows a 1/x2 power law. These power laws are universal in the sense that they are independent of the dominance and inbreeding coefficient, and also characterize the SFS during the sweep. Additionally, we find that the derived allele frequency where the SFS shifts from the 1/x to 1/x2 law, is inversely proportional to the selection strength: thus under strong selection, the SFS follows the 1/x2 dependence for most allele frequencies, resembling a rapidly expanding neutral population. When clonal interference is pervasive, the SFS immediately post-fixation becomes U-shaped and is better explained by the equilibrium SFS of selected sites. Our results will be important in developing statistical methods to infer the timing and strength of recent selective sweeps in asexual populations, genomic regions that lack recombination, and clonally propagating tumor populations.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Drosophila maternal-effect gene abnormal oocyte (ao) does not repress histone gene expression 果蝇的母性效应基因异常卵母细胞（ao）不会抑制组蛋白基因的表达

bioRxiv - Genetics Pub Date : 2024-09-18 DOI: 10.1101/2024.09.17.613536

Risa Takenaka, Sierra M Simmerman, Casey A Schmidt, Eric H Albanese, Leila E Rieder, Harmit Singh Malik

{"title":"The Drosophila maternal-effect gene abnormal oocyte (ao) does not repress histone gene expression","authors":"Risa Takenaka, Sierra M Simmerman, Casey A Schmidt, Eric H Albanese, Leila E Rieder, Harmit Singh Malik","doi":"10.1101/2024.09.17.613536","DOIUrl":"https://doi.org/10.1101/2024.09.17.613536","url":null,"abstract":"The abnormal oocyte (ao) gene of Drosophila melanogaster is a maternal-effect lethal gene previously identified as encoding a transcriptional regulator of core histones. However, background genetic mutations in existing ao mutant strains could compromise their utility in manipulating histone levels. To distinguish the true ao pheno-type from background effects, we created two new ao reagents: a CRISPR/Cas9-mediated knockout of the ao allele for genetic and molecular analyses and an epitope-tagged ao allele for cytological experiments. Using these rea-gents, we confirm previous findings that ao exhibits maternal-effect lethality, which can be rescued by either a decrease in the histone gene copy number or by Y chromosome heterochromatin. We also confirm that the Ao protein localizes to the histone locus bodies in ovaries. Our data also suggest that ao genetically interacts with the histone genes and heterochromatin, as previously suggested. However, contrary to prior findings, we find that ao does not repress core histone transcript levels. Thus, the molecular basis for ao-associated maternal-effect lethality remains unknown.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"190 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Variant classification guidelines for animals to objectively evaluate genetic variant pathogenicity 客观评估遗传变异致病性的动物变异分类指南

bioRxiv - Genetics Pub Date : 2024-09-18 DOI: 10.1101/2024.09.17.613537

Fréderique Boeykens, Marie Abitbol, Heidi Anderson, Iris Casselman, Caroline Dufaure de Citres, Jessica J. Hayward, Jens Häggström, Mark D Kittleson, Elvio Lepri, Ingrid Ljungvall, Maria Longeri, Leslie A Lyons, Åsa Ohlsson, Luc Peelman, Pascale Smets, Tommaso Vezzosi, Frank van Steenbeek, Bart J.G. Broeckx

{"title":"Variant classification guidelines for animals to objectively evaluate genetic variant pathogenicity","authors":"Fréderique Boeykens, Marie Abitbol, Heidi Anderson, Iris Casselman, Caroline Dufaure de Citres, Jessica J. Hayward, Jens Häggström, Mark D Kittleson, Elvio Lepri, Ingrid Ljungvall, Maria Longeri, Leslie A Lyons, Åsa Ohlsson, Luc Peelman, Pascale Smets, Tommaso Vezzosi, Frank van Steenbeek, Bart J.G. Broeckx","doi":"10.1101/2024.09.17.613537","DOIUrl":"https://doi.org/10.1101/2024.09.17.613537","url":null,"abstract":"Assessing the pathogenicity of a disease-associated variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, lead to incorrect treatment and even life-ending decisions. Criteria to determine pathogenicity are not standardized, hence no guidelines for animal variants are available. Here, we developed and optimized the animal variant classification guidelines, based on those developed for humans by The American College of Medical Genetics and Genomics, and demonstrated a superior classification in animals. We described methods to develop datasets for benchmarking the criteria and identified the most optimal in silico variant effect predictor tools. As the reproducibility was high, we classified 72 known disease-associated variants in cats and 40 other disease-associated variants in eight additional species.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developmental transcriptomics in Pristionchus reveals the logic of a plasticity gene regulatory network Pristionchus 的发育转录组学揭示了可塑性基因调控网络的逻辑关系

bioRxiv - Genetics Pub Date : 2024-09-17 DOI: 10.1101/2024.09.12.612712

Shelley Reich, Tobias Loschko, Julie Jung, Samantha Nestel, Ralf J. Sommer, Michael S. Werner

{"title":"Developmental transcriptomics in Pristionchus reveals the logic of a plasticity gene regulatory network","authors":"Shelley Reich, Tobias Loschko, Julie Jung, Samantha Nestel, Ralf J. Sommer, Michael S. Werner","doi":"10.1101/2024.09.12.612712","DOIUrl":"https://doi.org/10.1101/2024.09.12.612712","url":null,"abstract":"Developmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. While significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematode Pristionchus pacificus has culminated in 30 genes which affect mouth-form plasticity. We also recently reported the critical window of environmental sensitivity, and therefore have clear expectations for when differential gene expression should matter. Here, we collated previous data into a gene-regulatory network (GRN), and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mouth-form mutants to assess the regulatory logic of plasticity. We found that only two genes in the GRN (eud-1 and seud-1/sult-1) are sensitive to the environment during the critical window. Interestingly, the time points of their sensitivity differ, suggesting that they act as sequential checkpoints. We also observed temporal constraint upon the transcriptional effects of mutating the GRN and revealed unexpected feedback between mouth-form genes. Surprisingly, expression of seud-1/sult-1, but not eud-1, correlated with mouth form biases across different strains and species. Finally, a comprehensive analysis of all samples identified metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene-expression comparisons across development in up to 14 different conditions. Collectively, our results suggest that mouth-form plasticity evolved a constrained, two-tiered logic to integrate environmental information leading up to the final developmental decision.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporal Patterns of Gene Expression During Development of a Complex Colony Morphology 复杂菌落形态发育过程中基因表达的时空模式

bioRxiv - Genetics Pub Date : 2024-09-16 DOI: 10.1101/2024.09.14.613051

Gareth A. Cromie, Zhihao Tan, Michelle Hays, Amy Sirr, Aimée M. Dudley

{"title":"Spatiotemporal Patterns of Gene Expression During Development of a Complex Colony Morphology","authors":"Gareth A. Cromie, Zhihao Tan, Michelle Hays, Amy Sirr, Aimée M. Dudley","doi":"10.1101/2024.09.14.613051","DOIUrl":"https://doi.org/10.1101/2024.09.14.613051","url":null,"abstract":"Clonal communities of single celled organisms, such as bacterial or fungal colonies and biofilms, are spatially structured, with subdomains of cells experiencing differing environmental conditions. In the development of such communities, cell specialization is not only important to respond and adapt to the local environment but has the potential to increase the fitness of the clonal community through division of labor. Here, we examine colony development in a yeast strain (F13) that produces colonies with a highly structured “ruffled” phenotype in the colony periphery and an unstructured “smooth” phenotype in the colony center. We demonstrate that in the F13 genetic background deletions of transcription factors can either increase (dig1Δ, sfl1Δ) or decrease (tec1Δ) the degree of colony structure. To investigate the development of colony structure, we carried out gene expression analysis on F13 and the three deletion strains using RNA-seq. Samples were taken early in colony growth (day2), which precedes ruffled phenotype development in F13, and from the peripheral and central regions of colonies later in development (day5), at which time these regions are structured and unstructured (respectively) in F13. We identify genes responding additively and non-additively to the genotype and spatiotemporal factors and cluster these genes into a number of different expression patterns. We identify clusters whose expression correlates closely with the degree of colony structure in each sample and include genes with known roles in the development of colony structure. Individual deletion of 26 genes sampled from different clusters identified 5 with strong effects on colony morphology (BUD8, CIS3, FLO11, MSB2 and SFG1), all of which eliminated or greatly reduced the structure of the F13 outer region.","PeriodicalId":501246,"journal":{"name":"bioRxiv - Genetics","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0