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Yeast: Molecular and Cell Biology, 2nd Edition

Horst Feldmann (Editor)
ISBN: 978-3-527-33252-6
464 pages
November 2012, ©2012, Wiley-Blackwell
Yeast: Molecular and Cell Biology, 2nd Edition (3527332529) cover image
Finally, a stand-alone, all-inclusive textbook on yeast biology. 

Based on the feedback resulting from his highly successful monograph, Horst Feldmann has totally rewritten the contents to produce a comprehensive, student-friendly textbook on the topic. The scope has been widened, with almost double the content so as to include all aspects of yeast biology, from genetics via cell biology right up to biotechnology applications. The cell and molecular biology sections have been vastly expanded, while information on other yeast species has been added, with contributions from additional authors. Naturally, the illustrations are in full color throughout, and the book is backed by a complimentary website.

The resulting textbook caters to the needs of an increasing number of students in biomedical research, cell and molecular biology, microbiology and biotechnology who end up using yeast as an important tool or model organism.
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Preface XVII

Authors XIX

1 Introduction 1

1.1 Historical Aspects 1

1.2 Yeast as a Eukaryotic Model System 1

Further Reading 3

2 Yeast Cell Architecture and Functions 5

2.1 General Morphology 5

2.2 Cell Envelope 6

2.2.1 Cell Wall 7

2.2.2 Plasma Membrane 8

2.3 Cytoplasm and Cytoskeleton 8

2.3.1 Yeast Cytoplasm 8

2.3.2 Yeast Cytoskeleton 9

2.3.2.1 Microtubules 9

2.3.2.2 Actin Structures 9

2.3.2.3 Motor Proteins 11

2.3.2.3.1 Myosins 12

2.3.2.3.2 Kinesins 13

2.3.2.3.3 Dynein 12

2.3.2.4 Other Cytoskeletal Factors 13

2.3.2.4.1 Proteins Interacting with the Cytoskeleton 13

2.3.2.4.2 Transport of Organellar Components 13

2.4 Yeast Nucleus 14

2.4.1 Overview 14

2.4.2 Nuclear Pore 14

2.4.2.1 Historical Developments 14

2.4.2.2 Current View of the Nuclear Pore 15

2.4.2.3 Yeast Nucleolus 17

2.4.3 Yeast Chromosomes 17

2.5 Organellar Compartments 17

2.5.1 ER and the Golgi Apparatus 18

2.5.2 Transport Vesicles 18

2.5.3 Vacuolar System 20

2.5.3.1 Yeast Vacuole 20

2.5.3.2 Vacuolar Degradation 21

2.5.4 Endocytosis and Exocytosis 21

2.5.5 Mitochondria 21

2.5.5.1 Mitochondrial Structure 21

2.5.6 Peroxisomes 22

Further Reading 23

3 Yeast Metabolism 25

3.1 Metabolic Pathways and Energy 25

3.2 Catabolism of Hexose Carbon Sources 25

3.2.1 Principal Pathways 25

3.2.2 Respiration Versus Fermentation 26

3.2.3 Catabolism of Other Sugars – Galactose 27

3.2.4 Metabolism of Non-Hexose Carbon Sources 28

3.3 Gluconeogenesis and Carbohydrate Biosynthesis 30

3.3.1 Gluconeogenesis 30

3.3.2 Storage Carbohydrates 30

3.3.2.1 Glycogen 30

3.3.2.2 Trehalose 31

3.3.3 Unusual Carbohydrates 31

3.3.3.1 Unusual Hexoses and Amino Sugars 31

3.3.3.2 Inositol and its Derivatives 32

3.3.3.3 N- and O-Linked Glycosylation 33

3.3.4 Structural Carbohydrates 34

3.4 Fatty Acid and Lipid Metabolism 35

3.4.1 Fatty Acids 35

3.4.2 Lipids 35

3.4.3 Glycolipids 36

3.4.3.1 Phosphatidylinositol and Derivatives 36

3.4.3.2 Sphingolipids 38

3.4.3.3 Glycosylphosphatidylinositol (GPI) 39

3.4.4 Isoprenoid Biosynthesis 40

3.5 Nitrogen Metabolism 42

3.5.1 Catabolic Pathways 42

3.5.2 Amino Acid Biosynthesis Pathways 44

3.5.2.1 Glutamate Family 44

3.5.2.2 Aspartate Family 44

3.5.2.3 Branched Amino Acids 45

3.5.2.4 Lysine 46

3.5.2.5 Serine, Cysteine, and Glycine 46

3.5.2.6 Alanine 46

3.5.2.7 Aromatic Amino Acids 46

3.5.2.8 Histidine 47

3.5.2.9 Amino Acid Methylation 47

3.6 Nucleotide Metabolism 48

3.6.1 Pyrimidine Derivatives 48

3.6.2 Purine Derivatives 48

3.6.3 Deoxyribonucleotides 50

3.6.4 Nucleotide Modification 50

3.7 Phosphorus and Sulfur Metabolism 51

3.7.1 Phosphate 51

3.7.2 Sulfur 52

3.7.2.1 Fixation and Reduction of Sulfate 52

3.7.2.2 Cycle of Activated Methyl Groups 53

3.8 Vitamins and Cofactors 53

3.8.1 Biotin 53

3.8.2 Thiamine 53

3.8.3 Pyridoxine 54

3.8.4 NAD 54

3.8.5 Riboflavin Derivatives 54

3.8.6 Pantothenic Acid and Coenzyme A 55

3.8.7 Folate 55

3.8.8 Tetrapyrroles 55

3.8.9 Ubiquinone (Coenzyme Q) 56

3.9 Transition Metals 57

Further Reading 58

4 Yeast Molecular Techniques 59

4.1 Handling of Yeast Cells 59

4.1.1 Growth of Yeast Cells 59

4.1.2 Isolation of Particular Cell Types and Components 59

4.2 Genetic Engineering and Reverse Genetics 59

4.2.1 Molecular Revolution 59

4.2.2 Transformation of Yeast Cells 61

4.2.2.1 Yeast Shuttle Vectors 61

4.2.2.2 Yeast Expression Vectors 62

4.2.2.3 Secretion of Heterologous Proteins from Yeast 63

4.2.2.4 Fluorescent Proteins Fused to Yeast Proteins 63

4.2.3 Yeast Cosmid Vectors 64

4.2.4 Yeast Artificial Chromosomes 65

4.3 More Genetic Tools from Yeast Cells 65

4.3.1 Yeast Two-Hybrid System 65

4.3.2 Yeast Three-Hybrid System 66

4.3.3 Yeast One-Hybrid (Matchmaker) System 67

4.4 Techniques in Yeast Genome Analyses 67

4.4.1 Microarrays 67

4.4.1.1 DNA-Based Approaches 67

4.4.1.2 Proteome Analyses 68

4.4.2 Affinity Purification 70

4.4.3 Mass Spectrometry 70

Further Reading 72

5 Yeast Genetic Structures and Functions 73

5.1 Yeast Chromosome Structure and Function 73

5.1.1 Yeast Chromatin 73

5.1.1.1 Organization of Chromatin Structure 73

5.1.1.2 Modification of Chromatin Structure 73

5.1.1.2.1 Modification of Histones 73

5.1.1.2.2 Remodeling Chromatin Structure Overview 81

5.1.2 Centromeres 85

5.1.3 Replication Origins and Replication 85

5.1.3.1 Initiation of Replication 85

5.1.3.2 Replication Machinery 88

5.1.3.2.1 DNA Polymerases 88

5.1.3.2.2 Replication and Replication Factors 89

5.1.3.2.3 Postreplication Repair and DNA Damage Tolerance 89

5.1.3.3 Replication and Chromatin 90

5.1.3.3.1 Chromatin Reorganization 90

5.1.3.3.2 Silencing and Boundaries 91

5.1.3.4 DNA Damage Checkpoints 93

5.1.3.4.1 Checkpoints During Replication 93

5.1.3.4.2 DSB Repair 94

5.1.4 Telomeres 96

5.1.5 Transposons in Yeast 98

5.1.5.1 Classes of Transposable Elements 98

5.1.5.2 Retrotransposons in S. cerevisiae 98

5.1.5.2.1 Ty Elements and their Genomes 98

5.1.5.2.2 Behavior of Ty Elements 99

5.1.5.2.3 Expression of Ty Elements 100

5.1.5.3 Ty Replication 101

5.1.5.4 Interactions between Ty Elements and their Host 102

5.2 Yeast tRNAs, Genes, and Processing 103

5.2.1 Yeast tRNAs 103

5.2.1.1 Yeast Led the Way to tRNA Structure 103

5.2.1.2 Yeast tRNA Precursors and Processing 105

5.2.2 Current Status of Yeast tRNA Research 106

5.2.2.1 Yeast tRNAs and their Genes 106

5.2.2.2 tRNA Processing and Maturation 106

5.2.2.3 Participation of tRNAs in an Interaction Network 109

5.2.2.3.1 Aminoacylation of tRNAs 109

5.2.2.3.2 Rules, Codon Recognition, and Specific tRNA Modification 111

5.2.2.3.3 Recognition of tRNAs in the Protein Biosynthetic Network 111

5.3 Yeast Ribosomes: Components, Genes, and Maturation 113

5.3.1 Historical Overview 113

5.3.2 Ribosomal Components 113

5.3.2.1 Ribosomal RNAs 113

5.3.2.2 Ribosomal Proteins 114

5.3.3 Components and Pathways of Yeast Ribosome Maturation 114

5.4 Messenger RNAs 116

5.4.1 First Approaches to the Structure of Yeast mRNAs 116

5.4.2 Introns and Processing of pre-mRNA 117

5.4.3 Provenance of Introns 121

5.5 Extrachromosomal Elements 121

5.5.1 Two Micron DNA 121

5.5.2 Killer Plasmids 121

5.5.3 Yeast Prions 121

5.6 Yeast Mitochondrial Genome 123

Further Reading 125

6 Gene Families Involved in Cellular Dynamics 127

6.1 ATP- and GTP-Binding Proteins 127

6.1.1 ATPases 127

6.1.1.1 P-Type ATPases 127

6.1.1.2 V-Type ATPases 127

6.1.1.3 Chaperones, Cochaperones, and Heat-Shock Proteins 128

6.1.1.3.1 HSP70 Family 128

6.1.1.3.2 HSP40 Family 129

6.1.1.3.3 HSP90 Family 129

6.1.1.3.4 HSP60 Family 132

6.1.1.3.5 HSP104 132

6.1.1.3.6 HSP26 and HSP42 132

6.1.1.3.7 HSP150 133

6.1.1.3.8 HSP31/32/33 133

6.1.1.3.9 HSP30 133

6.1.1.3.10 HSP10 133

6.1.1.3.11 Others 133

6.1.1.4 Other ATP-Binding Factors 133

6.1.2 Small GTPases and Their Associates 133

6.1.2.1 RAS Family 134

6.1.2.2 RAB Family 134

6.1.2.3 RHO/RAC Family 134

6.1.2.4 ARF Family 134

6.1.2.5 Ran GTPAse 136

6.1.3 G-Proteins 136

6.1.3.1 Mating Pheromone G-Protein 136

6.1.3.2 Gpr1-Associated G-Protein 137

6.1.3.3 RGS Family 137

6.1.3.4 G-Like Proteins 137

6.2 Regulatory ATPases: AAA and AAAþ Proteins 138

6.2.1 ATP-Dependent Proteases 138

6.2.2 Membrane Fusion Proteins 139

6.2.3 Cdc48 139

6.2.4 Peroxisomal AAA Proteins 139

6.2.5 Katanin and Vps4p 139

6.2.6 Dynein 139

6.2.7 DNA Replication Proteins 140

6.2.8 RuvB-Like Proteins 140

6.2.9 Other AAAþ Yeast Proteins 140

6.3 Protein Modification by Proteins and Programmed Protein Degradation 141

6.3.1 Ubiquitin–Proteasome System (UPS) 141

6.3.1.1 Initial Discoveries 141

6.3.1.2 Ubiquitin and Factors in the Ubiquitin-Mediated Pathway 141

6.3.1.3 E3 Ubiquitin Ligases 142

6.3.1.3.1 HECT-Type Ligases 142

6.3.1.3.2 RING Finger-Type Ligases 143

6.3.1.3.3 Functions of Selected E3 Ligases 144

6.3.1.4 Ubiquitin-Specific Proteases 147

6.3.2 Yeast Proteasomes 147

6.3.2.1 Initial Discoveries 147

6.3.2.2 Structure of the Proteasome 148

6.3.2.3 Regulation of Yeast Proteasome Activity 148

6.3.3 More Functions for Ubiquitin 150

6.3.4 Ubiquitin-Like Proteins (ULPs) and Cognate Factors 151

6.3.4.1 SUMO 151

6.3.4.2 Rub1 152

6.3.4.3 Ubiquitin Domain Proteins 152

6.3.4.4 Substrate Delivery to the Proteasome 153

6.4 Yeast Protein Kinases and Phosphatases 153

6.4.1 Protein Kinases in Yeast 153

6.4.1.1 PKA as a Prototype Kinase 153

6.4.1.2 Yeast Possesses a Multitude of Kinases 153

6.4.2 Protein Phosphatases in Yeast 158

6.5 Yeast Helicase Families 159

6.5.1 RNA Helicases in Yeast 166

6.5.1.1 Structures and Motifs 166

6.5.1.2 Functions of RNA Helicases in Yeast 167

6.5.2 DNA Helicases in Yeast 168

6.5.2.1 Structures and Motifs 168

6.5.2.2 Functions of DNA Helicases 168

6.5.2.2.1 ASTRA Complex 170

6.5.2.2.2 RAD Epistasis Group 170

6.5.2.2.3 Monomeric DNA Helicases 170

Further Reading 173

7 Yeast Growth and the Yeast Cell Cycle 175

7.1 Modes of Propagation 175

7.1.1 Vegetative Reproduction 175

7.1.1.1 Budding 175

7.1.1.2 Septins and Bud Neck Filaments 178

7.1.1.3 Spindle Pole Bodies and their Dynamics 179

7.1.2 Sexual Reproduction 181

7.1.3 Filamentous Growth 181

7.1.4 Yeast Aging and Cell Death 183

7.1.4.1 Yeast Lifespan 183

7.1.4.2 Yeast Apoptosis 184

7.1.4.2.1 External Triggers of Yeast Apoptosis 184

7.1.4.2.2 Endogenous Triggers of Yeast Apoptosis 185

7.1.4.2.3 Regulation of Yeast Apoptosis 185

7.2 Cell Cycle 186

7.2.1 Dynamics and Regulation of the Cell Cycle 186

7.2.1.1 Some Historical Notes 186

7.2.1.2 Periodic Events in the First Phases of the Cell Cycle 188

7.2.1.2.1 CDK and Cyclins 189

7.2.1.2.2 Regulation of the CDK/Cyclin System 190

7.2.2 Dynamics and Regulation of Mitosis 193

7.2.2.1 Sister Chromatids: Cohesion 193

7.2.2.2 Spindle Assembly Checkpoint 196

7.2.2.3 Chromosome Segregation 198

7.2.2.4 Regulation of Mitotic Exit 199

7.3 Meiosis 200

7.3.1 Chromosome Treatment During Meiosis 200

7.3.2 Regulation of Meiosis 201

7.3.2.1 Early, Middle, and Late Meiotic Events 201

7.3.2.2 Sporulation 202

7.3.3 Checkpoints in Meiosis 202

Further Reading 204

8 Yeast Transport 207

8.1 Intracellular Protein Sorting and Transport 207

8.1.1 “Signal Hypothesis” 207

8.1.2 Central Role of the ER 207

8.1.3 Intracellular Protein Trafficking and Sorting 208

8.1.3.1 Some History 208

8.1.3.2 Membrane Fusions 210

8.1.3.2.1 SNAREs and All That 210

8.1.3.2.2 Small GTPases and Transport Protein Particles 211

8.1.3.3 ER-Associated Protein Degradation 214

8.1.3.4 Golgi Network 215

8.1.3.5 Vacuolar Network 216

8.1.3.5.1 Autophagy 216

8.1.3.5.2 Cytoplasm-to-Vacuole Targeting (CVT) Pathway 217

8.1.3.5.3 Nomenclature in Autophagy and Cvt 218

8.1.3.6 Endocytosis and the Multivesicular Body (MVB) Sorting Pathway 218

8.1.3.6.1 Endocytosis by Vesicles Budding from the Membrane 218

8.1.3.6.2 Endosomal Sorting Complexes Required for Transport (ESCRTs) 219

8.1.3.7 Exocytosis 221

8.2 Nuclear Traffic 221

8.2.1 Nuclear Transport 221

8.2.2 Nuclear mRNA Quality Control 223

8.2.3 Nuclear Export of mRNA 224

8.2.4 Nuclear Dynamics of tRNA 225

8.3 Membrane Transporters in Yeast 226

8.3.1 Transport of Cations 226

8.3.2 Channels and ATPases 226

8.3.2.1 Channels 226

8.3.2.2 ATP-Dependent Permeases 226

8.3.3 Ca2þ-Signaling and Transport Pathways in Yeast 227

8.3.3.1 Ca2þ Transport 227

8.3.3.2 Ca2þ -Mediated Control 228

8.3.3.3 Ca2þ and Cell Death 228

8.3.4 Transition Metal Transport 228

8.3.4.1 Iron 229

8.3.4.2 Copper 230

8.3.4.3 Zinc 231

8.3.4.4 Manganese 232

8.3.5 Anion Transport 232

8.3.5.1 Phosphate Transport 232

8.3.5.2 Transport of Other Anions 233

8.3.6 Nutrient and Ammonium Transport 233

8.3.6.1 Transport of Carbohydrates 233

8.3.6.2 Amino Acid Transport 234

8.3.6.3 Transport of Nucleotide Constituents/Nucleotide Sugars 234

8.3.6.4 Transport of Cofactors and Vitamins 234

8.3.6.5 Ammonium Transport 234

8.3.7 Mitochondrial Transport 235

8.3.7.1 Transport of Substrates 235

8.3.7.2 Electron Transport Chain 236

8.3.7.3 Proton Motive Force – ATP Synthase 239

Further Reading 240

9 Yeast Gene Expression 241

9.1 Transcription and Transcription Factors 241

9.2 RNA Polymerases and Cofactors 241

9.2.1 RNA Polymerase I 242

9.2.2 RNA Polymerase III 243

9.2.3 RNA Polymerase II 245

9.2.4 General Transcription Factors (GTFs) 246

9.2.4.1 TBP 246

9.2.4.2 TFIIA 247

9.2.4.3 TFIIB 247

9.2.4.4 TFIIE and TFIIF 247

9.2.4.5 TFIIH 247

9.2.4.6 TFIIS 247

9.2.4.7 TFIID 247

9.2.4.8 First Simplified Pictures of Transcription 247

9.2.5 Transcriptional Activators 248

9.2.5.1 TAFs 249

9.2.5.2 SRB/Mediator 249

9.2.5.3 Depicting Transcriptional Events 249

9.3 Transcription and its Regulation 251

9.3.1 Regulatory Complexes 251

9.3.1.1 SAGA 251

9.3.1.2 PAF Complex 252

9.3.1.3 CCR4–NOT Complex 252

9.3.1.4 Other Factors and Complexes 253

9.3.2 Modification of Chromatin During Polymerase II Transcription 254

9.3.2.1 Early Endeavors 254

9.3.2.2 Chromatin-Modifying Activities and Transcriptional Elongation 254

9.3.2.3 Models for Specific Chromatin Remodeling During Transcription 255

9.3.2.3.1 GAL4 System 256

9.3.2.3.2 PHO System 256

9.3.2.3.3 Other Studies 257

9.3.2.3.4 Global Nucleosome Occupancy 258

9.3.3 Nucleosome Positioning 259

9.4 DNA Repair Connected to Transcription 259

9.4.1 Nucleotide Excision Repair (NER) 259

9.4.2 Mismatch Repair 261

9.4.3 Base Excision Repair 261

9.5 Coupling Transcription to Pre-mRNA Processing 261

9.5.1 Polyadenylation 261

9.5.2 Generation of Functional mRNA 263

9.5.2.1 General Principles 263

9.5.2.2 Control and Pathways of mRNA Decay 265

9.5.2.2.1 Exosome-Mediated Pathways in Yeast 265

9.5.2.2.2 Nonsense-Mediated mRNA Decay (NMD) 267

9.6 Yeast Translation Apparatus 268

9.6.1 Initiation 269

9.6.2 Elongation and Termination 270

9.7 Protein Splicing – Yeast Inteins 271

Further Reading 271

10 Molecular Signaling Cascades and Gene Regulation 273

10.1 Ras–cAMP Signaling Pathway 273

10.2 MAP Kinase Pathways 275

10.2.1 Mating-Type Pathway 275

10.2.2 Filamentation/Invasion Pathway 278

10.2.3 Control of Cell Integrity 279

10.2.4 High Osmolarity Growth Pathway 280

10.2.5 Spore Wall Assembly Pathway 280

10.2.6 Influence of MAP Kinase Pathways in Cell Cycle Regulation 281

10.3 General Control by Gene Repression 281

10.3.1 Ssn6–Tup1 Repression 281

10.3.2 Activation and Repression by Rap1 283

10.4 Gene Regulation by Nutrients 283

10.4.1 TOR System 283

10.4.1.1 Structures of the TOR Complexes 283

10.4.1.2 Signaling Downstream of TORC1 284

10.4.1.3 Signaling Branches Parallel to TORC1 286

10.4.1.4 Internal Signaling of TORC1 286

10.4.1.5 TOR and Aging 286

10.4.2 Regulation of Glucose Metabolism 287

10.4.2.1 Major Pathway of Glucose Regulation 287

10.4.2.2 Alternative Pathway of Glucose Regulation 289

10.4.3 Regulation of Galactose Metabolism 289

10.4.4 General Amino Acid Control 290

10.4.5 Regulation of Arginine Metabolism 293

10.5 Stress Responses in Yeast 294

10.5.1 Temperature Stress and Heat-Shock Proteins 294

10.5.2 Oxidative and Chemical Stresses 295

10.5.2.1 AP-1 Transcription Factors in Yeast 295

10.5.2.2 STRE-Dependent System 296

10.5.2.3 PDR: ABC Transporters 296

10.5.3 Unfolded Protein Response 298

Further Reading 299

11 Yeast Organellar Biogenesis and Function 301

11.1 Mitochondria 301

11.1.1 Genetic Biochemistry of Yeast Mitochondria 301

11.1.2 Mitochondrial Functions Critical to Cell Viability 303

11.1.2.1 Superoxide Dismutase 303

11.1.2.2 Iron Homeostasis 304

11.1.3 Biogenesis of Mitochondria: Protein Transport 305

11.1.3.1 Presequence Pathway and the MIA Pathway 307

11.1.3.2 Membrane Sorting Pathway: Switch Between TIM22 and TIM23 307

11.1.3.3 b-Barrel Pathway 308

11.1.3.4 Endogenous Membrane Insertion Machinery 308

11.1.4 Mitochondrial Quality Control and Remodeling 308

11.2 Peroxisomes 310

11.2.1 What They Are – What They Do 310

11.2.2 Protein Import and Cargo 311

Further Reading 312

12 Yeast Genome and Postgenomic Projects 313

12.1 Yeast Genome Sequencing Project 313

12.1.1 Characteristics of the Yeast Genome 314

12.1.2 Comparison of Genetic and Physical Maps 315

12.1.3 Gene Organization 315

12.1.3.1 Protein-Encoding Genes 315

12.1.3.2 Overlapping ORFs, Pseudogenes, and Introns 316

12.1.4 Genetic Redundancy: Gene Duplications 317

12.1.4.1 Duplicated Genes in Subtelomeric Regions 317

12.1.4.2 Duplicated Genes Internal to Chromosomes 318

12.1.4.3 Duplicated Genes in Clusters 318

12.1.5 Gene Typification and Gene Families 318

12.1.5.1 Gene Functions 318

12.1.5.2 tRNA Multiplicity and Codon Capacity in Yeast 319

12.1.5.2.1 tRNA Gene Families 319

12.1.5.2.2 Correlation of tRNA Abundance to Gene Copy Number 320

12.1.5.2.3 tRNA Gene Redundancy and Codon Selection in Yeast 320

12.2 Yeast Functional Genomics 322

12.2.1 Early Functional Analysis of Yeast Genes 322

12.2.2 Yeast Transcriptome 322

12.2.2.1 Genomic Profiling 322

12.2.2.2 Protein–DNA Interactions 323

12.2.3 Yeast Proteome 324

12.2.3.1 Protein Analysis 324

12.2.3.2 Proteome Chips 325

12.2.3.3 Protein–Protein Interactions and Protein Complexes: The Yeast Interactome 325

12.2.4 Yeast Metabolic Networks 327

12.2.4.1 Metabolic Flux 327

12.2.4.2 Yeast Metabolic Cycle 328

12.2.5 Genetic Landscape of a Cell 329

12.2.6 Data Analysis Platforms 329

12.3 Yeast Systems Biology 330

12.4 Yeast Synthetic Biology 332

Further Reading 334

13 Disease Genes in Yeast 335

13.1 General Aspects 335

13.1.1 First Approaches 335

13.1.2 Recent Advances 335

13.2 Trinucleotide Repeats and Neurodegenerative Diseases 341

13.2.1 Neurodegenerative Disorders 342

13.2.2 Huntington’s Disease 342

13.2.3 Parkinson’s Disease 343

13.2.4 Alzheimer’s Disease and Tau Biology 343

13.2.5 Other Proteinopathies 344

13.3 Aging and Age-Related Disorders 344

13.4 Mitochondrial Diseases 344

Further Reading 346

14 Yeasts in Biotechnology 347
Paola Branduardi and Danilo Porro

14.1 Introduction 347

14.1.1 Biotechnology Disciplines 347

14.1.2 Microorganisms in Biotechnology 348

14.2 Yeasts: Natural and Engineered Abilities 348

14.2.1 Yeast as a Factory 348

14.2.2 Natural Production 349

14.2.2.1 Commercial Yeasts 349

14.2.2.2 Food Yeast 349

14.2.2.3 Feed Yeasts 351

14.2.2.4 Yeast Extract 351

14.2.2.5 Autolysed Yeast 352

14.2.3 Engineered Abilities: Recombinant Production of the First Generation 352

14.2.3.1 Metabolic Engineering 352

14.2.3.2 Engineered Products 353

14.2.3.2.1 Isoprene Derivatives 353

14.2.3.2.2 Pigments 354

14.2.3.2.3 Other Valuable Biocompounds 354

14.2.3.2.4 Small Organic Compounds 356

14.2.3.2.5 Biofuels 357

14.2.3.2.6 Further Developments 358

14.2.4 Engineered Abilities: Recombinant Production of the Second Generation 358

14.3 Biopharmaceuticals from Healthcare Industries 359

14.3.1 Human Insulin 359

14.3.2 Other Biopharmaceuticals 361

14.4 Biomedical Research 362

14.4.1 Humanized Yeast Systems for Neurodegenerative Diseases 363

14.4.1.1 Parkinson’s Disease 363

14.4.1.2 Huntington’s Disease 363

14.4.1.3 Alzheimer’s Disease 363

14.4.2 Yeast Models of Human Mitochondrial Diseases 363

14.4.3 Yeast Models for Lipid-Related Diseases 364

14.4.4 Yeasts and Complex Genomes 364

14.5 Environmental Technologies: Cell Surface Display 364

14.6 Physiological Basis for Process Design 366

14.6.1 Process Development 367

14.6.2 Production Process 368

Further Reading 370

15 Hemiascomycetous Yeasts 371
Claude Gaillardin

15.1 Selection of Model Genomes for the Genolevures and Other Sequencing Projects 371

15.2 Ecology, Metabolic Specificities, and Scientific Interest of Selected Species 373

15.2.1 Candida glabrata – A Pathogenic Cousin of S. cerevisiae 373

15.2.2 Lachancea (Saccharomyces) kluyveri – An Opportunistic Anaerobe 375

15.2.3 Kluyveromyces lactis – A Respiro-Fermentative Yeast 376

15.2.4 Eremothecium (Ashbya) gossypii – A Filamentous Plant Pathogen 377

15.2.5 Debaryomyces hansenii – An Osmotolerant Yeast 378

15.2.6 Scheffersomyces (Pichia) stipitis – A Xylose-Utilizing Yeast 379

15.2.7 Komagataella (Pichia) pastoris – A Methanol-Utilizing Yeast 380

15.2.8 Blastobotrys (Arxula) adeninivorans – A Thermotolerant Yeast 381

15.2.9 Yarrowia lipolytica – An Oily Yeast 382

15.3 Differences in Architectural Features and Genetic Outfit 383

15.3.1 Genome Sizes and Global Architecture 383

15.3.2 Chromosome Architecture and Synteny 383

15.3.3 Arrangements of Genetic Elements 385

15.3.3.1 Replication Origins, Centromeres, and Telomeres 385

15.3.3.2 Gene Arrays 386

15.3.3.2.1 Megasatellites 386

15.3.3.2.2 Tandem Gene Arrays 387

15.3.3.2.3 Yeast Pseudogenes 387

15.3.4 Gene Families and Diversification of the Protein Repertoires 388

15.3.4.1 Biological Divergence 388

15.3.4.2 Diversification of the Gene Repertoire 389

15.3.5 tRNAs and rRNAs 391

15.3.6 Other Noncoding RNAs 392

15.3.7 Introns 393

15.3.8 Transposons 395

15.3.9 Mitochondrial DNA 395

15.3.10 DNA Plasmids 397

15.4 Molecular Evolution of Functions 397

15.4.1 Proteome Diversification and Loss or Gain of Functions 398

15.4.1.1 Loss and Relocalization of Pathways 398

15.4.1.2 Diversification of Paralogs 398

15.4.1.3 Horizontal Transfers 398

15.4.1.4 Evolution of Cell Identity 399

15.4.1.5 Heterochromatin, Gene Silencing, and RNA Interference 399

15.4.2 Changes in Transcriptional Regulation 400

15.4.2.1 Evolution of the GAL Regulon 400

15.4.2.2 Glucose Effects and Adaptation to Anoxic Conditions 401

15.4.2.3 Stress Responses 401

15.4.2.4 Recruitment of New Transcription Factors and DNA-Binding Sites 402

15.4.2.5 New Combinatorial Controls 403

15.4.2.6 Nucleosome Positioning in Evolution 403

15.4.3 Changes in Post-Transcriptional Regulations 404

Further Reading 405

16 Yeast Evolutionary Genomics 407
Bernard Dujon

16.1 Specificities of Yeast Populations and Species, and their Evolutionary Consequences 407

16.1.1 Species, Complexes, and Natural Hybrids 407

16.1.2 Reproductive Trade-Offs 408

16.1.3 Preference for Inbreeding 409

16.1.4 Population Structures Examined at the Genomic Level 410

16.1.5 Loss of Heterozygosity and Formation of Chimeras 410

16.1.6 Asymmetrical Growth of Clonal Populations 411

16.2 Gene Duplication Mechanisms and their Evolutionary Consequences 412

16.2.1 Gene Clusters 412

16.2.2 Whole-Genome Duplication 413

16.2.3 Segmental Duplications 414

16.2.4 Retrogenes and Dispersed Paralogs 414

16.3 Other Mechanisms of Gene Formation and Acquisition of Novel Functions 415

16.3.1 Introgression 415

16.3.2 Horizontal Gene Transfer from Bacterial Origin 416

16.3.3 De Novo Gene Formation 417

16.3.4 Integration of Other Sequences in Yeast Chromosomes 418

Further Reading 419

17 Epilog: The Future of Yeast Research 421

Appendix A: References 423

Appendix B: Glossary of Genetic and Taxonomic Nomenclature 425

Appendix C: Online Resources useful in Yeast Research 427

Appendix D: Selected Abbreviations 429

Index 433

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Horst Feldmann studied Organic Chemistry in Cologne and did his PhD in this discipline. From 1962 to 1967 he worked at the Institute of Genetics in Cologne. In 1974 he became Professor of Physiological Chemistry at the Medical Faculty in Munich. His pioneering research included sequencing yeast tRNA. He extensively studied tRNA and protein biogenesis, yeast retrotransposons and mitochondrial genome and was a co-ordinator in the EU project "Sequencing and Analysis of the Yeast Genome". From 1971 until 2007 he was one of the organizers of the International "Spetses Summer Schools on Molecular and Cell Biology". Horst Feldmann was a member of the Board of FEBS and served as chairman of the Advanced Courses Committee, Secretary of the Prize "Biochemical Analysis" and the Head of SFB "Mechanisms and Factors in Gene Regulation". He has also served as member of a number of different committees, namely the DFG, IUBMB, DISNAT (German-Israeli cooperation). He is also an Honorary Member of Hellenic Society for Biochemistry and Biophysics. In 1996 he received the FEBS Diplôme d'Honneur.
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“The book is an example of writing with the minimum of redundancy and maximum information, organised into a versatile illustrated review on modern yeast biology.”  (British Journal of Biomedical Science, 1 October 2012)

“In summary, this well-written work is a significant achievement that will reward both casual reading and more detailed study - recommended!.”  (Society for General Microbiology, 25 February 2013)

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