Дисертації з теми "Saccharomyces cerevisiae genome codes"
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Rowley, Neil K. "Studies on the Saccharomyces cerevisiae genome." Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361615.
Повний текст джерелаGreig, Duncan. "Sex, species and Saccharomyces cerevisiae." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301401.
Повний текст джерелаNovarina, D. "MECHANISMS PRESERVING GENOME INTEGRITY IN SACCHAROMYCES CEREVISIAE." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/215589.
Повний текст джерелаSHANMUGAN, MUTHU KUMAR. "EXPLORING GENOME INTEGRITY PATHWAYS IN SACCHAROMYCES CEREVISIAE." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229912.
Повний текст джерелаBleackley, Mark Robert. "Transition metal tolerance and the Saccharomyces cerevisiae genome." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/30821.
Повний текст джерелаMinchell, Nicola E. "DNA topological stress during DNA replication in Saccharomyces cerevisiae." Thesis, University of Sussex, 2019. http://sro.sussex.ac.uk/id/eprint/81222/.
Повний текст джерелаCook, Kristen. "Regulation of Genome-Wide Transcriptional Stress Responses in Saccharomyces cerevisiae." Thesis, Harvard University, 2011. http://dissertations.umi.com/gsas.harvard:10032.
Повний текст джерелаCoissac, Éric. "Analyse structurale et fonctionnelle du genome de la levure saccharomyces cerevisiae." Paris 6, 1996. http://www.theses.fr/1996PA066520.
Повний текст джерелаTeixeira, Maria Teresa. "Organisation du noyau et analyse fonctionnelle du genome de saccharomyces cerevisiae." Paris 11, 2000. http://www.theses.fr/2000PA112033.
Повний текст джерелаAmai, Takamitsu. "Development of genome editing technology of mitochondrial DNA in Saccharomyces cerevisiae." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263707.
Повний текст джерелаPowers, Ralph Wilson. "Genome-wide screens reveal that reduced TOR signaling extends chronological and replicative life span in S. cerevisiae /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/5044.
Повний текст джерелаLeadbitter, Matthew. "Genome-wide study to investigate the organisation of global genome nucleotide excision repair in Saccharomyces cerevisiae." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/54442/.
Повний текст джерелаDriscoll, R. "Saccharomyces cerevisiae proteins Rtt109p and Esc2p : two novel regulators of genome stability." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598656.
Повний текст джерелаHuang, Meng-Er. "Contribution a l'etude du genome de la levure saccharomyces cerevisiae : chromosome 10." Paris 7, 1993. http://www.theses.fr/1993PA077268.
Повний текст джерелаPORCU, GIAMPIERO. "Genome wide analysis of effects of protein farnesylation inhibition on saccharomyces cerevisiae." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2008. http://hdl.handle.net/2108/559.
Повний текст джерелаAnticancer agents based on inhibition of farnesyl-transferase (FTIs) inhibit Ras prenylation and tumour growth in a wide range of malignancy in preclinical studies. However, when tested in clinical trials, FTIs showed their beneficial effects only when used in combinatorial therapies. Despite a decade of studies, how FTIs promote morphological reversion remains unclear as they clearly impact multiple pathways and/or other prenylated proteins than Ras. Here, we combined genomic approaches to assess the primary yeast response to FTase inhibitor I (FTI-I) by using this compound at doses at which yeast viability and Ras farnesylation is poorly affected. Genomic expression profiling of wild-type cells show an FTI-I action in changing transcription of genes involved in microtubule polymerization/depolymerization and chromosome stability and in multi drug resistance (MDR). Chemical profiling of the EUROSCARF yeast deletion collection confirmed these data. In addition, it implicates the p-21 activated kinases (PAKs) in FTI-I resistance. Overall this study highlight the importance of carefully address the multi drug resistance response when using FTIs in clinical therapy and indicates PAKs as second target to use in combinatorial therapies.
Lantermann, Alexandra. "Comparison of Genome-Wide Nucleosome Positioning Mechanisms in Schizosaccharomyces pombe and Saccharomyces cerevisiae." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-118784.
Повний текст джерелаPegram, Kirsty Elizabeth. "The role of FOB 1 sumoylation in maintaining genome stability in saccharomyces cerevisiae." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528293.
Повний текст джерелаGarduño, Bertha Veronića. "Cbf1 regulates chromatin remodelling of the Saccharomyces cerevisiae genome at multiple binding sites." Thesis, University of Oxford, 1999. http://ora.ox.ac.uk/objects/uuid:be76ba21-1336-4ac8-9da3-918fd58d5908.
Повний текст джерелаJennings, Ezra (Ezra Gray) 1971. "Genome-wide expression and location profiling in Saccharomyces cerevisiae : experimental and graphical analysis." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/29919.
Повний текст джерелаIncludes bibliographical references.
Genome-wide expression analysis was used to identify genes whose expression depends on the functions of key components of the transcription initiation machinery in yeast. Components of the RNA polymerase II holoenzyme, the general transcription factor TFIID, and the SAGA chromatin modification complex were found to have roles in expression of distinct sets of genes. The results reveal an unanticipated level of regulation which is superimposed on that due to gene-specific transcription factors, a novel mechanism for co-ordinate regulation of specific sets of genes when cells encounter limiting nutrients, and evidence that the ultimate targets of signal transduction pathways can be identified within the initiation apparatus. Understanding how DNA-binding proteins control global gene expression and chromosomal maintenance requires knowledge of the chromosomal locations where these proteins function in vivo. We developed a microarray method that reveals the genome wide location of DNA-bound proteins and used this method to monitor binding of gene specific transcription activators in yeast. A combination of location and expression profiles was used to identify genes whose expression is directly controlled by Ga14 as cells respond to changes in carbon source, and by Thi2 in the absence or presence of thiarnin. The results identify pathways that are coordinately regulated by these regulators and reveal novel functions for these regulators. Understanding a transcriptional network such as these will be useful in constructing a cellular regulatory network map. The use of microarray technology has created new challenges in data analysis for biologists. Visual displays can greatly facilitate the analysis and communication of large quantities of data. We have created a Graphical Display Suite (GDS) that consists of a collection of tools to assist in the visualization of data from genome-wide experiments in S. cerevisiae. The ODS is web-accessible, easy to use, and additional components can easily be incorporated into its interface. This suite of tools has proven to be useful in revealing important biological insights.
by Ezra Jennings.
Ph.D.
Hui, Sheng. "The analysis of metabolism in saccharomyces cerevisiae with genome-scale gene expression data." HKBU Institutional Repository, 2005. http://repository.hkbu.edu.hk/etd_ra/640.
Повний текст джерелаOjo, Tolulope A. "Characterization of new mutants in the 16S ribosomal subunit region of the mitochondrial genome of Saccharomyces cerevisiae /." Connect to online version, 2006. http://ada.mtholyoke.edu/setr/websrc/pdfs/www/2006/148.pdf.
Повний текст джерелаLévesque, Nancy. "Deciphering the function of chromatin modifiers in genome regulation and maintenance in Saccharomyces cerevisiae." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43352.
Повний текст джерелаHarris, M. R. "G1/S transcriptional regulation in Saccharomyces cerevisiae integrates cell cycle progression and genome stability." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1419003/.
Повний текст джерелаMAFTAHI, MOHAMED. "Contribution au sequencage et a l'analyse fonctionnelle du genome de la levure saccharomyces cerevisiae." Paris 7, 1997. http://www.theses.fr/1997PA077134.
Повний текст джерелаGillet-Markowska, Alexandre. "Etude quantitative des variations structurelles des chromosomes chez Saccharomyces cerevisiae." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066233/document.
Повний текст джерелаThe accumulation of chromosomal rearrangements also called Structural Variations (SV) is a major contributor to the transformation of tumoral cells and to the constitution of intratumoral heterogeneity. We have developed a bio-informatic tool that can now provide a sharp image of SV that occur in the human genome. We have demonstrated the existence of SV present in low proportions in different supposedly clonal cell populations showing that the rates of SV formation could be greatly underestimated. In parallel, we have shown that the level of instability of the genome depends on predisposition factors. To identify those, we have developed genetic assays to measure the rate of SV in yeast that will allow us to identify new genes controlling the stability of the genome using large scale linkage analysis. These regulators represent new gene-candidates involved in the development of cancer in human as the determinants involved in DNA metabolism are very conserved between yeast and mammals
Tsaponina, Olga. "Regulation of ribonucleotide reductase and the role of dNTP pools in genomic stability in yeast Saccharomyces cerevisiae." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-43978.
Повний текст джерелаMartos, Alexandre. "Relocalisation expérimentale de gènes mitochondriaux au noyau : un éclairage nouveau sur l'évolution du génome mitochondrial." Thesis, Bordeaux 2, 2012. http://www.theses.fr/2012BOR22003/document.
Повний текст джерелаDespite the nuclear relocation of most genes of the ancestral procaryotic genome which gave birth to mitochondria, a small set of genes still remains into the organite after 2 billions years of evolution. The reasons for this maintenance of mitochondrial genome are currently not clear. I studied these questions by experimenting artificial relocations of mitochondrial genes in the yeast Saccharomyces cerevisiae. We managed, for the first, to functionally express the ATP9 gene from the nucleus, which encodes a small hydrophobic essential subunit of the proton chanel of the ATP synthase. Mostly mitochondrial within eukaryotes like S.cerevisiae, this gene can be found in the nuclear genome in most metazoans, chlorophyceans green algae and ascomycota filamentous fungi like Podospora anserina. Our results show that the hydrophobicity of the Atp9p subunit has to be decreased to be imported into the mitochondria from the cytosol. We also identified some adaptations optimizing the expression of the relocated ATP9 gene. It seems that if the ATP9 gene relocation is possible within the yeast, yet it is a complex and difficult process. Such an evolution has only few chances to occur and to be maintained by natural selection, unless it could confer some advantage to the organism. We have confirmed this hypothesis in a study made on P.anserina, in which we showed that the natural ATP9 relocation to the nucleus that appeared during its evolution allowed the setting up of specific regulations modulating the ATP synthase needs during the life-cycle of this fungus. The results presented here lead us to introduce a new hypothesis postulating that the variations of the set of genes contained in the mitochondrial genome are influenced not only by the constraints generated by their products structure, but also by the lifestyle of the organism
Tran, Grant. "Modeling drug efficacy in the tumour microenvironment with Saccharomyces cerevisiae genome-wide screens in hypoxic conditions." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/60210.
Повний текст джерелаPharmaceutical Sciences, Faculty of
Graduate
Schlecht, HeÌleÌ€ne. "Investigating the correlation between genome location, ectopic recombination and chromosome organisation during meiosis in Saccharomyces cerevisiae." Thesis, University of Sheffield, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398663.
Повний текст джерелаHarbison, Christopher T. 1973. "Genome-wide analysis of transcriptional expression programs, regulatory networks and Cis-regulatory sequences in Saccharomyces cerevisiae." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/28933.
Повний текст джерелаIncludes bibliographical references.
Historically, knowledge of gene-specific transcription has been accumulated by the study of the individual genetic and physical interactions between transcriptional regulators and the genes they regulate, often requiring considerable time and effort. Microarray technology now enables investigation of gene expression at the level of the entire genome, allowing researchers access to rich datasets and promising new levels of depth in the understanding of transcriptional regulation. Our lab has made use of these technologies both to measure the levels of all mRNA transcripts within a population of cells, as well as to locate the regions within the genome that are bound by transcriptional regulators. Such studies not only allow for the functional annotation of both genes and regulators, but can also provide clues about the identity of the regulatory regions within DNA, the structure of global regulatory networks and the regulation of DNA-binding proteins. These and other insights are presented here based on our genome-wide studies of transcriptional regulation in the yeast Saccharomyces cerevisiae.
by Christopher T. Harbison.
Ph.D.
Jones, Hope. "Genetic Characterization and Analysis of Cis and Trans-elements That Facilitate Genome Stability in Saccharomyces cerevisiae." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/193584.
Повний текст джерелаBiteau, Nicolas. "Faisabilité du séquençage systématique d'un chromosome : stratégies et exploration du génome de Saccharomyces cerevisiae." Bordeaux 2, 1993. http://www.theses.fr/1993BOR28241.
Повний текст джерелаCoi, Anna Lisa. "A genome based approach to characterize genes involved in yeast adaptation to Sherry-like wines’ biological ageing." Thesis, Montpellier, SupAgro, 2014. http://www.theses.fr/2014NSAM0005/document.
Повний текст джерелаWine fermentation and flor ageing are performed by two groups of the yeast Saccharomyces cerevisiae, with very different lifestyles. In this thesis we have studied the genome of flor yeast in comparison to wine yeast in order to unravel their specificities. We have first selected 16 strains (8 wine and 8 flor) from France, Hungary, Italy and Spain in order to sequence their genome sequence on an Illumina HiSeq2000 platform. Three flor strains and two wine strains were haploidized in order to obtain a set of haploid flor strains for the molecular evaluation of different targets. We developed as well a synthetic media mimicking wine for that purpose. From the genome sequence we have drawn a phylogeny that showed that flor yeasts represent a specific lineage of yeast, different from the wine strains lineage, and identified divergent regions. These regions contain genes involved in key functions and several associated with velum growth. Remarkably, many genes involved in FLO11 regulation such as MAP kinase, or Ras/PKA pathways were mutated among flor strains and many variations were encountered in genes involved in metal homeostasis such as zinc and divalent metal transporters. A transcriptome analysis comparing one flor and one wine yeast on our wine synthetic media revealed expression differences associated to floculins and hexose transport, but also suggested that flor yeast P3-D5 face a zinc and inositol deficiency, whereas wine yeast K1 presented mitochondrial defects. The impact of allelic variation of several genes coding for the high affinity zinc transporter (ZRT1), and the major pyruvate decarboxylase (PDC1) has been evaluated in order to assess their role in the flor phenotype
Mischo, Hannah. "Disengaging Polymerases : Transcriptional termination by RNA polymerase II in Saccharomyces cerevisiae and the maintenance of genome integrity." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514968.
Повний текст джерелаColby, E. R. "Creating site-specific abasic sites in the genome of Saccharomyces cerevisiae to analyse replication-associated lesion bypass." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1419675/.
Повний текст джерелаWu, Jingyan. "A Genome-wide Analysis to Identify and Characterize Novel Genes Involved in tRNA Biology in Saccharomyces cerevisiae." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429197786.
Повний текст джерелаTuck, Alex Charles. "Genome-wide identification of non-canonical targets of messenger RNA synthesis and turnover factors in Saccharomyces cerevisiae." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/11719.
Повний текст джерелаTreu, Laura. "A genomic and transcriptomic approach to characterize oenological Saccharomyces cerevisiae strains." Doctoral thesis, Università degli studi di Padova, 2012. http://hdl.handle.net/11577/3422965.
Повний текст джерелаIl genere Saccharomyces comprende un gran numero di microrganismi di interesse tecnologico, utilizzati ad esempio per la produzione di bevande fermentate, biocarburanti e per la panificazione. La selezione naturale unita alla domesticazione ha determinato una pressione selettiva che ha modificato il genoma di questi lieviti producendo un ampio numero di ceppi diversi con fenotipi specializzati. Negli ultimi anni centinaia di ceppi sono stati caratterizzati dal punto di vista fenotipico ma una correlazione tra il fenotipo e il genotipo non è stata ancora completamente chiarita. L’analisi del sequenziamento genomico è un passo cruciale per ottenere una descrizione globale del contenuto genico e per evidenziare le differenze tra i ceppi. In questo studio sono stati sequenziati i genomi degli omozigoti derivati da quattro ceppi ecotipici di S. cerevisiae isolati da grappoli fermentati di Prosecco e Raboso Piave utilizzando sequenziatori di Nuova Generazione. Numerosi strumenti informatici sono stati utilizzati e sviluppati per adempire al complesso compito del finishing. Inoltre una dettagliata panoramica dell’espressione genica in 5 ceppi di vinificazione e 1 di laboratorio è stata effettuata utilizzando la tecnica RNA-seq con la metodologia SOLiD. I lieviti sono stati cresciuti in mosto sintetico in bioreattori controllati e dei campioni sono stati prelevati durante il processo fermentativo. I risultati hanno rivelato un profilo trascrizionale caratteristico dell’adattamento dei ceppi enologici allo stress dell’ambiente di vinificazione. Un confronto tra le differenze nelle sequenze promotoriali tra i ceppi e il successivo effetto a catena sull’espressione genica è stato considerato e i risultati evidenziano una maggior influenza della variabilità delle tandem repeat rispetto alle mutazioni sui siti di binding dei fattori di trascrizione. Infine utilizzando dei modelli statistici siamo riusciti a correlare le caratteristiche genetiche dei ceppi con le loro proprietà metaboliche e ad avere una visione globale dell’abilità di fermentazione dei diversi ceppi.
Peter, Jackson. "Dissection de la relation génotype-phénotype par des études d'association chez Saccharomyces cerevisiae." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ064/document.
Повний текст джерелаElucidating the genetic origin of phenotypic diversity among individuals within the same species is essential to understand evolution. Using whole genome sequences of 1,011 Saccharomyces cerevisiae isolates, my work sought to describe intraspecific genetic variation and investigate of its phenotypic consequences. Doing so, I obtained a precise view of the evolutionary history of S. cerevisiae. Phenotypic characterization provided the opportunity to perform genotype-phenotype genome-wide association studies with unprecedented power. I then focused on the evaluation of the parameters influencing genome-wide association studies, the appreciation of the limits of such an approach, and ways to circumvent them
TIAN, GUO-LIANG. "Recherches sur la structure et l'organisation du genome mitochondrial de la levure saccharomyces douglasii et d'un genome mitochondrial chimerique s. Douglasii et s. Cerevisiae." Paris 6, 1993. http://www.theses.fr/1993PA066260.
Повний текст джерелаSchulze, Julia Maria. "Genome-wide analysis of chromatin modification patterns and their functional associations with major cellular processes in Saccharomyces cerevisiae." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/29154.
Повний текст джерелаChu, Hui-Yi. "Genome-wide Investigation of Cellular Functions for tRNA Nucleus-Cytoplasm Trafficking in the Yeast Saccharomyces cerevisiae." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1343397048.
Повний текст джерелаJain, Shveta. "Genome-wide analysis of kinases and phosphatases reveal an essential MAP kinase involved in pexophagy in Saccharomyces cerevisiae." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC IP addresses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p1453663.
Повний текст джерелаTitle from first page of PDF file (viewed July 28, 2008). Available via ProQuest Digital Dissertations. Includes bibliographical references.
Dauban, Lise. "Organisation du génome par le complexe cohésine chez la levure Saccharomyces cerevisiae." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30100.
Повний текст джерелаCohesin is an evolutionary-conserved complex composed of a ring capable of DNA entrapment and of auxiliary proteins regulating its association with DNA. On the one hand, cohesin confers sister chromatid cohesion required for their proper segregation and on the other hand it establishes and maintains chromatin looping. Chromatin loops are crucial for assembly of topological domains, gene expression and genome stability. However, mechanisms driving their establishment remain to be elucidated. According to loop extrusion model, cohesin would capture small loops and enlarge them by extruding DNA throughout its ring. This model predicts that loop size would depend on both cohesin residence time on DNA and on its processivity. Deciphering cohesin regulation is thus fundamental to understand chromosome biology. In this study, we showed that mitotic chromosome arms of yeast Saccharomyces cerevisiae are organised in cohesin-dependent chromatin loops. We studied the role of cohesin regulatory subunits Pds5, Wpl1 and Eco1 on loop establishment. Our data show that Pds5 inhibits loop expansion via Wpl1 and Eco1. As previously described in mammals, Wpl1 counteracts loop expansion by dissociating cohesin from DNA. Our results suggest that Eco1 would inhibit cohesin translocation on DNA, required for loop expansion. We then studied how these proteins contribute to the organisation of the ribosomal DNA array (rDNA), a cohesin-rich, highly transcribed sequence segregated away from the rest of the genome. Our data point toward a central role for Pds5 in organising this genomic region, independently of Wpl1 and Eco1. To study in detail rDNA spatial organisation, we developed a dedicated image analysis to assess its organisation in three dimensions. We have unveiled an underlying organisation for rDNA, made by a succession of small domains spatially organised by cohesin. This study opens large perspectives towards a better understanding of cohesin regulation in genome organisation
Lee, Ming-Ta. "Analysis of genome stability in mutants defective for the SUMO isopeptidase Smt4/Ulp2 /." Diss., UC access only, 2009. http://proquest.umi.com/pqdweb?index=6&did=1907279801&SrchMode=2&sid=2&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1270053784&clientId=48051.
Повний текст джерелаIncludes abstract. Includes bibliographical references (leaves 213-243). Issued in print and online. Available via ProQuest Digital Dissertations.
Humphryes, Neil. "Global genome nucleotide excision repair factors and the ubiquitin-proteasome system regulate the DNA damage response in Saccharomyces cerevisiae." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/55468/.
Повний текст джерелаDelahodde, Agnès. "Activites arn-maturasique et adn-endonucleasique de deux proteines introniques homologues du genome mitochondrial de la levure saccharomyces cerevisiae." Paris 6, 1988. http://www.theses.fr/1988PA066185.
Повний текст джерелаLouvet, Olivier. "Analyse fonctionnelle de l'ORF YBR264c identifié lors du séquençage systématique du génome de la levure Saccharomyces Cerevisiae." Bordeaux 2, 1998. http://www.theses.fr/1998BOR28557.
Повний текст джерелаD'Angiolo, Melania Jennifer. "Étude des mécanismes moléculaires de l'évolution du génome chez la levure bourgeonnante Saccharomyces cerevisiae." Electronic Thesis or Diss., Université Côte d'Azur, 2021. http://theses.univ-cotedazur.fr/2021COAZ6001.
Повний текст джерелаGenomes are progressively modified during their evolution leading to gene content variation, recombination, mutation and genetic exchange among species/subpopulations. The advent of next-generation sequencing technologies and their cost reduction increased the number of genomes available for evolutionary studies, opening the way to understand the molecular mechanisms involved in genome evolution. In this work, I used the budding yeast Saccharomyces cerevisiae as model organism to investigate two important aspects of genome evolution: the origin of interspecies introgressions and telomere evolution.An introgression is the flow of genetic material between populations and it results from ancient hybridization events followed by repeated backcrossings with one of the parental populations. In the first part of my PhD, I studied a lineage of S. cerevisiae strains isolated from the wastewater of olive oil production (Alpechin), carrying abundant introgressions from the sister species S. paradoxus, and a natural S. cerevisiae/S. paradoxus hybrid, with 50% genome contribution from each parent, carrying abundant regions of loss-of-heterozygosity (LOH). I derived an accurate genetic map of LOHs in the hybrid and compared their position to the introgressions in the Alpechin strains, to infer their evolutionary relations. I found that LOH and introgressions overlapped and shared the same S. paradoxus ancestry, indicating that LOHs are the direct origins of introgressions in the Alpechin lineage. I proposed a model for the origin of yeast introgressions in which LOH regions allow interspecies hybrids to overcome sterility, which constitutes the main barrier to introgressions' onset in reproductively isolated species, such as yeasts, and validated the reliability of my model using experimental and computational techniques.In the second part of my PhD, I studied the extent of telomere diversity in S. cerevisiae and the outcome of chronic telomeric stress on cellular fitness. In a first project, I estimated telomere length in over 900 strains isolated around the world and observed remarkable variation. Strains isolated in wild habitats had shorter telomeres than domesticated ones. I performed a genome-wide association study that revealed novel genetic variants possibly regulating telomere length. I also pinpointed private loss-of-function mutations in known telomere length maintenance genes that could explain the very long/short telomeres of certain lineages. Moreover, I used multiple phenotypic datasets available for this collection to look for non-genetic factors associated to telomere length variation, and discovered an association between mitochondrial metabolism and telomeres in wild strains.In a second project, I performed experimental evolution of engineered yeasts synthetizing human telomeric DNA repeats at their chromosome-ends. I evolved telomere-humanized strains through mutation accumulation lines (MALs) to minimize selection, and I characterized the detrimental effects caused by telomeres' reshaping. During MALs, humanized yeasts gradually slowed their growth, shortened chronological lifespan and had higher mutation rate and genome instability. Next, I submitted MALs to adaptive evolution by multiple serial transfers (STs) of large population sizes, to map mutations that counteract their fitness decline. After multiple STs, most humanized lines recovered fitness thanks to the independent occurrence of mutations in the DNA-damage response pathway. Overall, my work contributed to elucidate the molecular mechanisms driving genome evolution, by providing a plausible model for introgression evolution in reproductively isolated species and by giving an unprecedented overview of the impact of the variation of telomere DNA length and sequence on global organismal fitness
Mendez, Jamie Elizabeth. "Investigation of Hsf1 Interacting Partners via a Genome-wide Yeast Two-hybrid Screen." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4543.
Повний текст джерела