Genomic mapping of complex traits across species demands integrating genetics and statistics. In particular, because it is easily interpreted, the R 2 statistic is commonly used in quantitative trait locus (QTL) mapping studies to measure the proportion of phenotypic variation explained by molecular markers. Mixed models with random polygenic effects have been used in complex trait dissection in different species. However, unlike fixed linear regression models, linear mixed models have no well-established R 2 statistic for assessing goodness-of-fit and prediction power. Our objectives were to assess the performance of several R 2 -like statistics for a linear mixed model in association mapping and to identify any such statistic that measures model-data agreement and provides an intuitive indication of QTL effect. Our results showed that the likelihood-ratio-based R 2 (R LR 2 ) satisfies several critical requirements proposed for the R 2 -like statistic. As R LR 2 reduces to the regular R 2 for fixed models without random effects other than residual, it provides a general measure for the effect of QTL in mixed-model association mapping. Moreover, we found that R LR 2 can help explain the overlap between overall population structure modeled as fixed effects and relative kinship modeled though random effects. As both approaches are derived from molecular marker information and are not mutually exclusive, comparing R LR Researchers in many disciplines use linear regression models widely. The R 2 statistic, the coefficient of determination, is one of the most frequently used measures of prediction power and goodness-of-fit for simple linear regression models (Draper and Smith, 1981;Everitt, 2002). In the literature on genetics, researchers often report R 2 values of newly identified genetic loci in addition to effect sizes and P-values (Lettre et al., 2008;Weedon et al., 2008). For nonstandard linear regression models, however, several competing R 2 -like statistics have been proposed to measure prediction power and goodness-of-fit (Buse, 1973;Magee, 1990;Xu, 2003;Kramer, 2005) but have not been used in genetics. Indeed, it is desirable to have a measure for general linear mixed models analogous in some ways to the R 2 of the linear regression model, which has a 'variation explained' interpretation.Association mapping searches the association between genetic markers and complex traits (for example disease susceptibility) based on populations (Hirschhorn and Daly, 2005). It complements linkage analysis in mapping the genetic basis of complex traits. Mixed models have long been used in genetic research (Henderson, 1984;Lynch and Walsh, 1998), and the mixed-model association mapping methods were developed to account for complex population structure (Meuwissen et al., 2002;Yu et al., 2006;Malosetti et al., 2007). Although statistics like deviance and the Bayesian Information Criterion (BIC) (Schwarz, 1978) can be used to select models (Broman and Speed, 2002;Littell et al., 2006), many researchers desire a R 2 -like stat...
Like other intracellular eukaryotic phytopathogens, the devastating rice blast fungus Magnaporthe (Pyricularia) oryzae first infects living host cells by elaborating invasive hyphae (IH) surrounded by a plant-derived membrane. This forms an extended biotrophic interface enclosing an apoplastic compartment into which fungal effectors can be deployed to evade host detection. M. oryzae also forms a focal, plant membrane-rich structure, the biotrophic interfacial complex (BIC), that accumulates cytoplasmic effectors for translocation into host cells. Molecular decision-making processes integrating fungal growth and metabolism in host cells with interface function and dynamics are unknown. Here, we report unanticipated roles for the M. oryzae Target-of-Rapamycin (TOR) nutrient-signaling pathway in mediating plant-fungal biotrophic interface membrane integrity. Through a forward genetics screen for M. oryzae mutant strains resistant to the specific TOR kinase inhibitor rapamycin, we discovered IMP1 encoding a novel vacuolar protein required for membrane trafficking, V-ATPase assembly, organelle acidification and autophagy induction. During infection, Δimp1 deletants developed intracellular IH in the first infected rice cell following cuticle penetration. However, fluorescently labeled effector probes revealed that interface membrane integrity became compromised as biotrophy progressed, abolishing the BIC and releasing apoplastic effectors into host cytoplasm. Growth between rice cells was restricted. TOR-independent autophagy activation in Δimp1 deletants (following infection) remediated interface function and cell-to-cell growth. Autophagy inhibition in wild type (following infection) recapitulated Δimp1. In addition to vacuoles, Imp1GFP localized to IH membranes in an autophagy-dependent manner. Collectively, our results suggest TOR-Imp1-autophagy branch signaling mediates membrane homeostasis to prevent catastrophic erosion of the biotrophic interface, thus facilitating fungal growth in living rice cells. The significance of this work lays in elaborating a novel molecular mechanism of infection stressing the dominance of fungal metabolism and metabolic control in sustaining long-term plant-microbe interactions. This work also has implications for understanding the enigmatic biotrophy to necrotrophy transition.
The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.
Classical genetic studies have identified many cases of pleiotropy where mutations in individual genes alter many different phenotypes. Quantitative genetic studies of natural genetic variants frequently examine one or a few traits, limiting their potential to identify pleiotropic effects of natural genetic variants. Widely adopted community association panels have been employed by plant genetics communities to study the genetic basis of naturally occurring phenotypic variation in a wide range of traits. High-density genetic marker data—18M markers—from 2 partially overlapping maize association panels comprising 1,014 unique genotypes grown in field trials across at least 7 US states and scored for 162 distinct trait data sets enabled the identification of of 2,154 suggestive marker-trait associations and 697 confident associations in the maize genome using a resampling-based genome-wide association strategy. The precision of individual marker-trait associations was estimated to be 3 genes based on a reference set of genes with known phenotypes. Examples were observed of both genetic loci associated with variation in diverse traits (e.g., above-ground and below-ground traits), as well as individual loci associated with the same or similar traits across diverse environments. Many significant signals are located near genes whose functions were previously entirely unknown or estimated purely via functional data on homologs. This study demonstrates the potential of mining community association panel data using new higher-density genetic marker sets combined with resampling-based genome-wide association tests to develop testable hypotheses about gene functions, identify potential pleiotropic effects of natural genetic variants, and study genotype-by-environment interaction.
Summary Fungal phytopathogens can suppress plant immune mechanisms in order to colonize living host cells. Identifying all the molecular components involved is critical for elaborating a detailed systems‐level model of plant infection probing pathogen weaknesses; yet, the hierarchy of molecular events controlling fungal responses to the plant cell is not clear. Here we show how, in the blast fungus Magnaporthe oryzae, terminating rice innate immunity requires a dynamic network of redox‐responsive E3 ubiquitin ligases targeting fungal sirtuin 2 (Sir2), an antioxidation regulator required for suppressing the host oxidative burst. Immunoblotting, immunopurification, mass spectrometry and gene functional analyses showed that Sir2 levels responded to oxidative stress via a mechanism involving ubiquitination and three antagonistic E3 ubiquitin ligases: Grr1 and Ptr1 maintained basal Sir2 levels in the absence of oxidative stress; Upl3 facilitated Sir2 accumulation in response to oxidative stress. Grr1 and Upl3 interacted directly with Sir2 in a manner that decreased and scaled with oxidative stress, respectively. Deleting UPL3 depleted Sir2 during growth in rice cells, triggering host immunity and preventing infection. Overexpressing SIR2 in the Δupl3 mutant remediated pathogenicity. Our work reveals how redox‐responsive E3 ubiquitin ligases in M. oryzae mediate Sir2 accumulation‐dependent antioxidation to modulate plant innate immunity and host susceptibility.
Background: Glioma is the most commonly diagnosed primary brain tumor. Dysregulation of long non-coding RNA (lncRNA) is associated with initiation and development of various cancer types including glioma. Methods: The relative expression of lncRNA was analyzed by real time-quantitative polymerase chain reaction (RT-qPCR). Cell counting kit (CCK-8) and flow cytometry analysis were applied to explore the role of prostate androgen-regulated transcript 1 (PART1) in glioma cell lines. Luciferase reporter assay, Western blotting and RT-qPCR were used to investigate the association between PART1, miR-190a-3p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in glioma cell lines. Results: In the present study, we elucidated a pivotal role and molecular mechanism of lncRNA PART1 in glioma cell lines. It was found that PART1 was significantly downregulated in glioma tissues compared to normal tissues according to TCGA data and our RT-qPCR results. The cell-based assays showed that PART1 suppressed cell proliferation and triggered cell apoptosis in glioma cell lines. PART1 inactivated PI3K/AKT cascade in glioma cell lines. Transfection of constitutively activated AKT (Myr-AKT) reversed PART1 induced cell apoptosis and cell growth arrest. The bioinformatic analysis suggested that miR-190a-3p might bind to PART1. In the dual luciferase reporter assay, we validated that PART1 directly bound to miR-190a-3p in glioma cell lines. Furthermore, there was a reciprocal repression between PART1 and miR-190-3p. In addition, PART1 upregulated PTEN and inactivated PI3K/AKT pathway in glioma cell lines. Moreover, silencing of PTEN reversed PART1 overexpression induced cell growth arrest and apoptosis. In glioma tissues, the Pearson Correlation analysis showed that there was a strong-positive correlation between PART1 level and PTEN mRNA level. Conclusion: Taken together, the current study revealed a PART1/miR-190a-3p/PTEN/PI3K/ AKT axis in glioma and provided novel insights for understanding the complex lncRNA-miRNA network in glioma.
Appressoria are important mediators of plant–microbe interactions. In the devastating rice blast pathogen Magnaporthe oryzae, appressorial morphogenesis from germ tube tips requires activated cAMP/PKA signaling and inactivated TOR signaling (TORoff). TORoff temporarily arrests G2 at a metabolic checkpoint during the single round of mitosis that occurs following germination. G2 arrest induces autophagy and appressorium formation concomitantly, allowing reprogression of the cell cycle to G1/G0 quiescence and a single appressorial nucleus. Inappropriate TOR activation abrogates G2 arrest and inhibits cAMP/PKA signaling downstream of cPKA. This results in multiple rounds of germ tube mitosis and the loss of autophagy and appressoria formation. How cAMP/PKA signaling connects to cell cycle progression and autophagy is not known. To address this, we interrogated TOR and cAMP/PKA pathways using signaling mutants, different surface properties, and specific cell cycle inhibitors and discovered a feed-forward subnetwork arising from TOR- and cAMP/PKA-signaling integration. This adenylate cyclase-cAMP-TOR-adenylate cyclase subnetwork reinforces cAMP/PKA-dependent appressorium formation under favorable environmental conditions. Under unfavorable conditions, the subnetwork collapses, resulting in reversible cell cycle-mediated germ tube growth regardless of external nutrient status. Collectively, this work provides new molecular insights on germ tube morphogenetic decision-making in response to static and dynamic environmental conditions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.