Orthologs of Human-Disease-Associated Genes in Plants Are Involved in Regulating Leaf Senescence

As eukaryotes, plants and animals have many commonalities on the genetic level, although they differ greatly in appearance and physiological habits. The primary goal of current plant research is to improve the crop yield and quality. However, plant research has a wider aim, exploiting the evolutionary conservatism similarities between plants and animals, and applying discoveries in the field of botany to promote zoological research that will ultimately serve human health, although very few studies have addressed this aspect. Here, we analyzed 35 human-disease-related gene orthologs in plants and characterized the genes in depth. Thirty-four homologous genes were found to be present in the herbaceous annual plant Arabidopsis thaliana and the woody perennial plant Populus trichocarpa, with most of the genes having more than two exons, including the ATM gene with 78 exons. More surprisingly, 27 (79.4%) of the 34 homologous genes in Arabidopsis were found to be senescence-associated genes (SAGs), further suggesting a close relationship between human diseases and cellular senescence. Protein–protein interaction network analysis revealed that the 34 genes formed two main subnetworks, and genes in the first subnetwork interacted with 15 SAGs. In conclusion, our results show that most of the 34 homologs of human-disease-associated genes in plants are involved in the leaf senescence process, suggesting that leaf senescence may offer a means to study the pathogenesis of human diseases and to screen drugs for the treat of diseases.

[1]  T. Honjo,et al.  Spermidine activates mitochondrial trifunctional protein and improves antitumor immunity in mice , 2022, Science.

[2]  Jingchu Luo,et al.  LSD 4.0: an improved database for comparative studies of leaf senescence , 2022, Molecular Horticulture.

[3]  J. Kirkland,et al.  Cellular senescence and senolytics: the path to the clinic , 2022, Nature Medicine.

[4]  Jianhua Zhu,et al.  Abiotic stress responses in plants , 2021, Nature Reviews Genetics.

[5]  K. Harter,et al.  The EDS1–PAD4–ADR1 node mediates Arabidopsis pattern-triggered immunity , 2021, Nature.

[6]  J. Nemunaitis,et al.  Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer , 2021, Journal of Hematology & Oncology.

[7]  Oriol Vinyals,et al.  Highly accurate protein structure prediction with AlphaFold , 2021, Nature.

[8]  Hongwei Guo,et al.  Leaf senescence: progression, regulation, and application , 2021, Molecular Horticulture.

[9]  Xiaodi Zhao,et al.  The TOR–EIN2 axis mediates nuclear signalling to modulate plant growth , 2021, Nature.

[10]  Hongwei Guo,et al.  An alternative splicing variant of PtRD26 delays leaf senescence by regulating multiple NAC transcription factors in Populus , 2021, The Plant cell.

[11]  Saurabh Yadav,et al.  Thioredoxins as Molecular Players in Plants, Pests, and Pathogens , 2021 .

[12]  Plant-Pest Interactions: From Molecular Mechanisms to Chemical Ecology: Chemical Ecology , 2021 .

[13]  E. Verdin,et al.  NAD+ metabolism and its roles in cellular processes during ageing , 2020, Nature Reviews Molecular Cell Biology.

[14]  Margaret H. Frank,et al.  TBtools - an integrative toolkit developed for interactive analyses of big biological data. , 2020, Molecular plant.

[15]  H. Nam,et al.  ATM Suppresses Leaf Senescence Triggered by DNA Double-strand Break through Epigenetic Control of Senescence-Associated Genes in Arabidopsis. , 2020, The New phytologist.

[16]  S. Khosla,et al.  The role of cellular senescence in ageing and endocrine disease , 2020, Nature Reviews Endocrinology.

[17]  Saurabh Yadav,et al.  Effects of Heat stress and molecular mitigation approaches in orphan legume, Chickpea , 2020, Molecular Biology Reports.

[18]  Pengcheng Wang,et al.  Target of Rapamycin Signaling in Plant Stress Responses1[OPEN] , 2020, Plant Physiology.

[19]  Jingchu Luo,et al.  LSD 3.0: a comprehensive resource for the leaf senescence research community , 2019, Nucleic Acids Res..

[20]  M. Blagosklonny.  Rapamycin for longevity: opinion article , 2019, Aging.

[21]  Ling Zhu,et al.  A phyB-PIF1-SPA1 kinase regulatory complex promotes photomorphogenesis in Arabidopsis , 2019, Nature Communications.

[22]  Steven L Salzberg,et al.  Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype , 2019, Nature Biotechnology.

[23]  E. Fielder,et al.  Mitochondrial dysfunction and cell senescence: deciphering a complex relationship , 2019, FEBS letters.

[24]  S. Stewart,et al.  Unmasking senescence: context-dependent effects of SASP in cancer , 2019, Nature Reviews Cancer.

[25]  Changcheng Xu,et al.  Dual Role for Autophagy in Lipid Metabolism in Arabidopsis[OPEN] , 2019, Plant Cell.

[26]  H. Nam,et al.  Leaf Senescence: Systems and Dynamics Aspects. , 2019, Annual review of plant biology.

[27]  J. Boeke,et al.  LINE-1 derepression in senescent cells triggers interferon and inflammaging , 2018, Nature.

[28]  R. Gutiérrez,et al.  Nitrate signaling and the control of Arabidopsis growth and development. , 2019, Current opinion in plant biology.

[29]  Gabriela Bitencourt-Ferreira,et al.  Docking with SwissDock. , 2019, Methods in molecular biology.

[30]  Hongwei Guo,et al.  Gene network analysis of senescence-associated genes in annual plants and comparative assessment of aging in perennials and animals , 2019, Translational Medicine of Aging.

[31]  J. Krstić,et al.  p53 Functions in Adipose Tissue Metabolism and Homeostasis , 2018, International journal of molecular sciences.

[32]  C. R. McClung,et al.  Circadian control of ORE1 by PRR9 positively regulates leaf senescence in Arabidopsis , 2018, Proceedings of the National Academy of Sciences.

[33]  S. Singh,et al.  Analysis of thermotolerance behaviour of five chickpea genotypes at early growth stages , 2018, Brazilian Journal of Botany.

[34]  Lei Wang,et al.  Cross Regulatory Network Between Circadian Clock and Leaf Senescence Is Emerging in Higher Plants , 2018, Front. Plant Sci..

[35]  D. Hwang,et al.  Time-evolving genetic networks reveal a NAC troika that negatively regulates leaf senescence in Arabidopsis , 2018, Proceedings of the National Academy of Sciences.

[36]  Hye Ryun Woo,et al.  Plant senescence: how plants know when and how to die , 2018, Journal of experimental botany.

[37]  Guido Kroemer,et al.  Spermidine in health and disease , 2018, Science.

[38]  Jian‐Kang Zhu.  Abiotic Stress Signaling and Responses in Plants , 2016, Cell.

[39]  B. Evans,et al.  Synergism between Inositol Polyphosphates and TOR Kinase Signaling in Nutrient Sensing, Growth Control, and Lipid Metabolism in Chlamydomonas[OPEN] , 2016, Plant Cell.

[40]  M. Vincentz,et al.  TOR Signaling and Nutrient Sensing. , 2016, Annual review of plant biology.

[41]  H. Nam,et al.  Age-associated circadian period changes in Arabidopsis leaves , 2016, Journal of experimental botany.

[42]  Sudhir Kumar,et al.  MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. , 2016, Molecular biology and evolution.

[43]  Jin Ok Yang,et al.  Programming of Plant Leaf Senescence with Temporal and Inter-Organellar Coordination of Transcriptome in Arabidopsis1[OPEN] , 2016, Plant Physiology.

[44]  Gang Fu,et al.  PubChem Substance and Compound databases , 2015, Nucleic Acids Res..

[45]  Y. van de Peer,et al.  The Plant Genome Integrative Explorer Resource: PlantGenIE.org. , 2015, The New phytologist.

[46]  Jer-Tsong Hsieh,et al.  The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with DAB2IP gene defect , 2015, International journal of radiation biology.

[47]  Bo Hu,et al.  GSDS 2.0: an upgraded gene feature visualization server , 2014, Bioinform..

[48]  Chao Xie,et al.  Fast and sensitive protein alignment using DIAMOND , 2014, Nature Methods.

[49]  A. Kukol,et al.  Molecular Modeling of Proteins , 2008, Methods Molecular Biology™.

[50]  J. Campisi,et al.  Senescence and apoptosis: dueling or complementary cell fates? , 2014, EMBO reports.

[51]  F. Neff,et al.  Longevity, aging and rapamycin , 2014, Cellular and Molecular Life Sciences.

[52]  Wen-Dar Lin,et al.  Translational Landscape of Photomorphogenic Arabidopsis[W] , 2013, Plant Cell.

[53]  Sara Hillenmeyer,et al.  Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements , 2013, Aging cell.

[54]  Y. Shiloh,et al.  The ATM protein kinase: regulating the cellular response to genotoxic stress, and more , 2013, Nature Reviews Molecular Cell Biology.

[55]  D. Voytas,et al.  Increasing frequencies of site-specific mutagenesis and gene targeting in Arabidopsis by manipulating DNA repair pathways , 2013, Genome research.

[56]  J. Sarkaria,et al.  ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells , 2012, Journal of Neuro-Oncology.

[57]  Günter P. Wagner,et al.  Measurement of mRNA abundance using RNA-seq data: RPKM measure is inconsistent among samples , 2012, Theory in Biosciences.

[58]  Philip N Benfey,et al.  Control of Arabidopsis root development. , 2012, Annual review of plant biology.

[59]  D. Sabatini,et al.  mTOR Signaling in Growth Control and Disease , 2012, Cell.

[60]  Tanya Z. Berardini,et al.  The Arabidopsis Information Resource (TAIR): improved gene annotation and new tools , 2011, Nucleic Acids Res..

[61]  Rasko Leinonen,et al.  The sequence read archive: explosive growth of sequencing data , 2011, Nucleic Acids Res..

[62]  M. Hall,et al.  Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control , 2011, Genetics.

[63]  Aurélien Grosdidier,et al.  SwissDock, a protein-small molecule docking web service based on EADock DSS , 2011, Nucleic Acids Res..

[64]  Chiara Tonelli,et al.  How Can Research on Plants Contribute to Promoting Human Health?[OA] , 2011, Plant Cell.

[65]  I. C. Lee,et al.  Age-dependent action of an ABA-inducible receptor kinase, RPK1, as a positive regulator of senescence in Arabidopsis leaves. , 2011, Plant & cell physiology.

[66]  X. Xu,et al.  The value of Arabidopsis research in understanding human disease states. , 2011, Current opinion in biotechnology.

[67]  K. Sleegers,et al.  Current status on Alzheimer disease molecular genetics: from past, to present, to future , 2010, Human molecular genetics.

[68]  Kathryn Moynihan Ramsey,et al.  Circadian Rhythms and Metabolic Syndrome: From Experimental Genetics to Human Disease , 2010, Circulation research.

[69]  Da-Qing Yang,et al.  The ATM Inhibitor KU-55933 Suppresses Cell Proliferation and Induces Apoptosis by Blocking Akt In Cancer Cells with Overactivated Akt , 2010, Molecular Cancer Therapeutics.

[70]  M. Ankarcrona,et al.  Mitochondria and Alzheimer’s disease: amyloid-β peptide uptake and degradation by the presequence protease, hPreP , 2009, Journal of bioenergetics and biomembranes.

[71]  D. Gomez-Casati,et al.  Nitric oxide accumulation is required to protect against iron‐mediated oxidative stress in frataxin‐deficient Arabidopsis plants , 2009, FEBS letters.

[72]  T. Tschaplinski,et al.  The F-Box Gene Family Is Expanded in Herbaceous Annual Plants Relative to Woody Perennial Plants1[W][OA] , 2008, Plant Physiology.

[73]  Rodrigo Lopez,et al.  Clustal W and Clustal X version 2.0 , 2007, Bioinform..

[74]  Nicholas J. Provart,et al.  An “Electronic Fluorescent Pictograph” Browser for Exploring and Analyzing Large-Scale Biological Data Sets , 2007, PloS one.

[75]  H. Nam,et al.  Leaf senescence. , 2007, Annual review of plant biology.

[76]  C. Brenner,et al.  NAD+ metabolism in health and disease. , 2007, Trends in biochemical sciences.

[77]  M. Gribskov,et al.  The Genome of Black Cottonwood, Populus trichocarpa (Torr. & Gray) , 2006, Science.

[78]  Ű. Langel,et al.  Two novel targeting peptide degrading proteases, PrePs, in mitochondria and chloroplasts, so similar and still different. , 2005, Journal of molecular biology.

[79]  J. Gershenzon,et al.  The secondary metabolism of Arabidopsis thaliana: growing like a weed. , 2005, Current opinion in plant biology.

[80]  N. Alexandrov,et al.  Features of Arabidopsis Genes and Genome Discovered using Full-length cDNAs , 2005, Plant Molecular Biology.

[81]  N. Curtin,et al.  Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM , 2004, Cancer Research.

[82]  R. Mittler,et al.  Reactive oxygen gene network of plants. , 2004, Trends in plant science.

[83]  N. Carter,et al.  A DNA damage checkpoint response in telomere-initiated senescence , 2003, Nature.

[84]  H. Brockenhuus von Löwenhielm,et al.  Isolation and Identification of a Novel Mitochondrial Metalloprotease (PreP) That Degrades Targeting Presequences in Plants* , 2002, The Journal of Biological Chemistry.

[85]  M. Koenig,et al.  Friedreich ataxia: a paradigm for mitochondrial diseases. , 2002, Current opinion in genetics & development.

[86]  F. Ausubel,et al.  MAP kinase signalling cascade in Arabidopsis innate immunity , 2002, Nature.

[87]  A. Gingras,et al.  The target of rapamycin (TOR) proteins , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[88]  The Arabidopsis Genome Initiative.  Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[89]  C. Szigyarto,et al.  Rapid degradation of the presequence of the f1beta precursor of the ATP synthase inside mitochondria. , 2000, The Biochemical journal.

[90]  M. R. Adams,et al.  Comparative genomics of the eukaryotes. , 2000, Science.

[91]  D. Mount,et al.  Repair of UV damage in plants by nucleotide excision repair: Arabidopsis UVH1 DNA repair gene is a homolog of Saccharomyces cerevisiae Rad1. , 2000, The Plant journal : for cell and molecular biology.

[92]  J. Vijg.  Somatic mutations and aging: a re-evaluation. , 2000, Mutation research.

[93]  M. Long,et al.  Intron-exon structures of eukaryotic model organisms. , 1999, Nucleic acids research.

[94]  Daniel A. Gschwend,et al.  Molecular docking towards drug discovery , 1996, Journal of molecular recognition : JMR.