Time filter

Source Type

Jansen A.,VIB Laboratory for Systems Biology | Verstrepen K.J.,VIB Laboratory for Systems Biology
Microbiology and Molecular Biology Reviews | Year: 2011

The DNA of eukaryotic cells is spooled around large histone protein complexes, forming nucleosomes that make up the basis for a high-order packaging structure called chromatin. Compared to naked DNA, nucleosomal DNA is less accessible to regulatory proteins and regulatory processes. The exact positions of nucleosomes therefore influence several cellular processes, including gene expression, chromosome segregation, recombination, replication, and DNA repair. Here, we review recent technological advances enabling the genome-wide mapping of nucleosome positions in the model eukaryote Saccharomyces cerevisiae. We discuss the various parameters that determine nucleosome positioning in vivo, including cis factors like AT content, variable tandem repeats, and poly(dA:dT) tracts that function as chromatin barriers and trans factors such as chromatin remodeling complexes, transcription factors, histone-modifying enzymes, and RNA polymerases. In the last section, we review the biological role of chromatin in gene transcription, the evolution of gene regulation, and epigenetic phenomena. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Brown C.A.,Harvard University | Murray A.W.,Harvard University | Verstrepen K.J.,Harvard University | Verstrepen K.J.,VIB Laboratory for Systems Biology
Current Biology | Year: 2010

Background: Subtelomeres, regions proximal to telomeres, exhibit characteristics unique to eukaryotic genomes. Genes residing in these loci are subject to epigenetic regulation and elevated rates of both meiotic and mitotic recombination. However, most genome sequences do not contain assembled subtelomeric sequences, and, as a result, subtelomeres are often overlooked in comparative genomics. Results: We studied the evolution and functional divergence of subtelomeric gene families in the yeast lineage. Our computational results show that subtelomeric families are evolving and expanding much faster than families that do not contain subtelomeric genes. Focusing on three related subtelomeric MAL gene families involved in disaccharide metabolism that show typical patterns of rapid expansion and evolution, we show experimentally how frequent duplication events followed by functional divergence yield novel alleles that allow the metabolism of different carbohydrates. Conclusions: Taken together, our computational and experimental analyses show that the extraordinary instability of eukaryotic subtelomeres supports rapid adaptation to novel niches by promoting gene recombination and duplication followed by functional divergence of the alleles. © 2010 Elsevier Ltd. All rights reserved.


Haesendonckx S.,University of Geneva | Haesendonckx S.,Catholic University of Leuven | Tudisca V.,University of Buenos Aires | Voordeckers K.,Catholic University of Leuven | And 4 more authors.
Biochemical Journal | Year: 2012

PDK1 (phosphoinositide-dependent protein kinase 1) phosphorylates and activates PKA (cAMP-dependent protein kinase) in vitro. Docking of the HM (hydrophobic motif) in the C-terminal tail of the PKA catalytic subunits on to the PIF (PDK1-interacting fragment) pocket of PDK1 is a critical step in this activation process. However, PDK1 regulation of PKA in vivo remains controversial. Saccharomyces cerevisiae contains three PKA catalytic subunits, TPK1, TPK2 and TPK3. We demonstrate that Pkh [PKB (protein kinase B)-activating kinase homologue] protein kinases phosphorylate the activation loop of each Tpk in vivo with various efficiencies. Pkh inactivation reduces the interaction of each catalytic subunit with the regulatory subunit Bcy1 without affecting the specific kinase activity of PKA. Comparative analysis of the in vitro interaction and phosphorylation of Tpks by Pkh1 shows that Tpk1 and Tpk2 interact with Pkh1 through an HM-PIF pocket interaction. Unlike Tpk1, mutagenesis of the activation loop site in Tpk2 does not abolish in vitro phosphorylation, suggesting that Tpk2 contains other, as yet uncharacterized, Pkh1 target sites. Tpk3 is poorly phosphorylated on its activation loop site, and this is due to the weak interaction of Tpk3 with Pkh1 because of the atypical HM found in Tpk3. In conclusion, the results of the present study show that Pkh protein kinases contribute to the divergent regulation of the Tpk catalytic subunits. © The Authors Journal compilation © 2012 Biochemical Society.


Voordeckers K.,VIB Laboratory for Systems Biology | Voordeckers K.,Catholic University of Leuven | Brown C.A.,VIB Laboratory for Systems Biology | Brown C.A.,Catholic University of Leuven | And 10 more authors.
PLoS Biology | Year: 2012

Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine. © 2012 Voordeckers et al.


Voordeckers K.,Catholic University of Leuven | Voordeckers K.,VIB Laboratory for Systems Biology | Verstrepen K.J.,Catholic University of Leuven | Verstrepen K.J.,VIB Laboratory for Systems Biology
Current Opinion in Microbiology | Year: 2015

Understanding how changes in DNA drive the emergence of new phenotypes and fuel evolution remains a major challenge. One major hurdle is the lack of a fossil record of DNA that allows linking mutations to phenotypic changes. However, the emergence of high-throughput sequencing technologies now allows sequencing genomes of natural and experimentally evolved microbial populations to study how mutations arise and spread through a population, how new phenotypes arise and how this ultimately leads to adaptation. Here, we highlight key studies that have increased our mechanistic understanding of evolution. We specifically focus on the model eukaryote Saccharomyces cerevisiae because its relatively short replication time, much-studied biology and available molecular toolbox have made it a prime model for molecular evolution studies. © 2015 The Authors.


Voordeckers K.,Catholic University of Leuven | Voordeckers K.,VIB Laboratory for Systems Biology | Pougach K.,Catholic University of Leuven | Pougach K.,VIB Laboratory for Systems Biology | And 2 more authors.
Current Opinion in Biotechnology | Year: 2015

Throughout evolution, regulatory networks need to expand and adapt to accommodate novel genes and gene functions. However, the molecular details explaining how gene networks evolve remain largely unknown. Recent studies demonstrate that changes in transcription factors contribute to the evolution of regulatory networks. In particular, duplication of transcription factors followed by specific mutations in their DNA-binding or interaction domains propels the divergence and emergence of new networks. The innate promiscuity and modularity of regulatory networks contributes to their evolvability: duplicated promiscuous regulators and their target promoters can acquire mutations that lead to gradual increases in specificity, allowing neofunctionalization or subfunctionalization. © 2015 The Authors.


Rezaei M.N.,Leuven Food Science and Nutrition Research Center oe | Verstrepen K.J.,VIB Laboratory for Systems Biology | Courtin C.M.,Leuven Food Science and Nutrition Research Center oe
Cereal Chemistry | Year: 2015

During dough fermentation, yeast (Saccharomyces cerevisiae) changes the physical properties of the dough matrix. In this study, we investigate if different yeast strains have an impact on dough rheology and on the gas holding capacity of fermenting dough. Furthermore, we analyze whether observed differences are linked to the metabolite profiles of the yeast strains. More specifically, the impact of 25 yeast strains on dough spread, dough fermentation properties, and dough metabolite profile was analyzed. Our results demonstrate large differences in the fermentation ability and metabolite profile of the 25 strains. Analysis of metabolites in fermented dough confirmed that acetic acid and succinic acid are likely responsible for the lowering of dough pH during fermentation and that the onset of CO2 release from dough is related to dough pH rather than to the volume of CO2 within the dough. Our results further suggest that the spread test is an inadequate tool to quantify rheological differences observed for strains with different fermentation profiles. © 2015 AACC International, Inc.


PubMed | CINVESTAV, Catholic University of Leuven and VIB Laboratory for Systems Biology
Type: Journal Article | Journal: PLoS genetics | Year: 2015

Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.


PubMed | VIB Laboratory for Systems Biology
Type: Journal Article | Journal: PLoS biology | Year: 2012

Gene duplications are believed to facilitate evolutionary innovation. However, the mechanisms shaping the fate of duplicated genes remain heavily debated because the molecular processes and evolutionary forces involved are difficult to reconstruct. Here, we study a large family of fungal glucosidase genes that underwent several duplication events. We reconstruct all key ancestral enzymes and show that the very first preduplication enzyme was primarily active on maltose-like substrates, with trace activity for isomaltose-like sugars. Structural analysis and activity measurements on resurrected and present-day enzymes suggest that both activities cannot be fully optimized in a single enzyme. However, gene duplications repeatedly spawned daughter genes in which mutations optimized either isomaltase or maltase activity. Interestingly, similar shifts in enzyme activity were reached multiple times via different evolutionary routes. Together, our results provide a detailed picture of the molecular mechanisms that drove divergence of these duplicated enzymes and show that whereas the classic models of dosage, sub-, and neofunctionalization are helpful to conceptualize the implications of gene duplication, the three mechanisms co-occur and intertwine.


PubMed | VIB Laboratory for Systems Biology
Type: Journal Article | Journal: Current genetics | Year: 2016

The brewers yeast Saccharomyces cerevisiae displays a much higher ethanol tolerance compared to most other organisms, and it is therefore commonly used for the industrial production of bioethanol and alcoholic beverages. However, the genetic determinants underlying this yeasts exceptional ethanol tolerance have proven difficult to elucidate. In this perspective, we discuss how different types of experiments have contributed to our understanding of the toxic effects of ethanol and the mechanisms and complex genetics underlying ethanol tolerance. In a second part, we summarize the different routes and challenges involved in obtaining superior industrial yeasts with improved ethanol tolerance.

Loading VIB Laboratory for Systems Biology collaborators
Loading VIB Laboratory for Systems Biology collaborators