Genomes 5:
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| Format: | Buch |
| Sprache: | English |
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Boca Raton ; London ; New York
CRC Press, Taylor & Francis Group
2023
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| Ausgabe: | Fifth edition |
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| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | xv, 530 Seiten Illustrationen, Diagramme |
| ISBN: | 9780367678661 0367678667 9780367674076 |
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Datensatz im Suchindex
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| adam_text | CONTENTS PREFACE ACKNOWLEDGEMENTS XIII XVII PARTI HOW GENOMES ARE STUDIED CHAPTER 1 GENOMES,TRANSCRIPTOMES, AND PROTEOMES 1.1 DNA Genes are made of DNA DNA is a polymer of nucleotides The discovery of the double helix The double helix is stabilized by base-pairing and base-stacking The double helix has structural flexibility 1.2 RNA AND THE TRANSCRIPTOME RNA is a second type of polynucleotide The RNA content of the cell Many RNAs are synthesized as precursor molecules There are different definitions of the transcriptome 1 2 3 5 б 8 9 11 11 12 13 15 1.3 PROTEINS ANDTHE PROTEOME 16 There are four hierarchical levels of protein structure 16 Amino acid diversity underlies protein diversity 16 The link between the transcriptome and the proteome 18 The genetic code is not universal 19 The link between the proteome and the biochemistry of the cell 20 SUMMARY 22 SHORT ANSWER QUESTIONS 23 IN-DEPTH PROBLEMS 23 FURTHER READING 24 CHAPTER 2 STUDYING DNA 25 2.1 ENZYMES FOR DNA MANIPULATION 26 The mode of action of a template-dependent DNA polymerase The types of DNA polymerase used in research Restriction endonucleases enable DNA molecules to be cut at defined positions Gel electrophoresis is used to examine the results of a restriction digest Interesting DNA fragments can be identified by Southern hybridization Ligases join DNA fragments together End-modification enzymes 2.2 THE POLYMERASE CHAINREACTION Carrying out a PGR The rate of product formation can be followed during a PGR PGR has many and diverse applications 2.3 DNA CLONING Why is gene cloning important? The simplest cloning
vectors are based on E. coli plasmids Bacteriophages can also be used as cloning vectors Vectors for longer pieces of DNA DNA can be cloned in organisms other than E. coli 26 28 29 32 33 34 35 35 36 37 38 38 39 39 41 44 45 SUMMARY 47 SHORT ANSWER QUESTIONS 48 IN-DEPTH PROBLEMS 48 FURTHER READING 49 CHAPTERS MAPPING GENOMES 51 3.1 WHY A GENOME MAP IS IMPORTANT Genome maps are needed in orderio sequence the more complex genomes Genome maps are not just sequencing aids 51 3.2 MARKERS FOR GENETIC MAPPING Genes were the first markers to be used RFLPs and SSLPs are examples of DNA markers Single-nucleotide polymorphisms are the most useful type of DNA marker 53 3.3 THE BASISTO GENETIC MAPPING 59 The principles of inheritance and the discovery of linkage 59 51 52 54 55 57
vi Contents Partial linkage is explained by the behavior of chromosomes during meiosis From partial linkage to genetic mapping 3.4 LINKAGE ANALYSIS WITH DIFFERENT TYPES OF ORGANISM Linkage analysis when planned breeding experiments are possible Gene mapping by human pedigree analysis Genetic mapping in bacteria The limitations of linkage analysis 3.5 PHYSICAL MAPPING BY DIRECT EXAMINATION OF DNA MOLECULES Conventional restriction mapping is only applicable to small DNA molecules Optical mapping can locate restriction sites in longer DNA molecules Optical mapping with fluorescent probes Further innovations extend the scope of optical mapping 3.6 PHYSICAL MAPPING BY ASSIGNING MARKERS TO DNA FRAGMENTS Any unique sequence can be used as an STS DNA fragments for STS mapping can be obtained as radiation hybrids A clone library can be used as the mapping reagent 60 63 64 64 66 67 69 Many prokaryotic genomes have been sequenced by the shotgun method Shotgun sequencing of eukaryotic genomes requires sophisticated assembly programs From contigs to scaffolds What is a genome sequence and do we always need one? 95 95 97 99 4.3 SEQUENCING THE HUMAN GENOME The Human Genome Project ֊ genome sequencing in the heroic age The human genome - genome sequencing in the modern age The Neanderthal genome - assembly of an extinct genome using the human sequence as a reference The human genome - new challenges 101 71 74 SUMMARY 108 SHORT ANSWER QUESTIONS 109 75 IN-DEPTH PROBLEMS 110 FURTHER READING 110 70 71 102 104 106 107 77 77 78 79 SUMMARY 80 SHORT ANSWER QUESTIONS 80 IN-DEPTH PROBLEMS 81
FURTHER READING 81 CHAPTER 4 SEQUENCING GENOMES 83 4.1 METHODOLOGY FOR DNA SEQUENCING Chain-termination sequencing of PCR products Illumina sequencing is the most popular short read method A variety of other short-read sequencing methods have been devised Single-molecule real-time sequencing provides reads up to 200 kb in length Nanopore sequencing is currently the longest long-read method 83 83 4.2 HOW TO SEQUENCE A GENOME The potential of the shotgun method was proven by the Haemophilus influenzae sequence 93 86 88 90 92 93 CHAPTER 5 GENOME ANNOTATION 113 5.1 GENOME ANNOTATION BY COMPUTER ANALYSIS OF THE DNA SEQUENCE 113 The coding regions of genes are open reading frames 113 Simple ORF scans are less effective with genomes of higher eukaryotes 114 Locating genes for noncoding RNA 116 Homology searches and comparative genomics give an extra dimension to gene prediction 117 5.2 GENOME ANNOTATION BY ANALYSIS OF GENE TRANSCRIPTS 119 Hybridization tests can determine if a fragment contains one or more genes 119 Methods are available for precise mapping of the ends of transcripts 120 Exon-intron boundaries can also be located with precision 121 5.3 ANNOTATION BY GENOME-WIDE RNA MAPPING 121 Tiling arrays enable transcripts to be mapped on to chromosomes or entire genomes 122 Transcript sequences can be directly mapped onto a genome 123 Obtaining transcript sequences by SAGE and CAGE 125
CONTENTS vii 5.4 GENOME BROWSERS 126 IN-DEPTH PROBLEMS 151 SUMMARY 128 FURTHER READING 152 SHORT ANSWER QUESTIONS 128 IN-DEPTH PROBLEMS 129 FURTHER READING 129 CHAPTER 6 IDENTIFYING GENE FUNCTIONS 6.1 COMPUTER ANALYSIS OF GENE FUNCTION Homology reflects evolutionary relationships Homology analysis can provide information on the function of a gene Identification of protein domains can help to assign function to an unknown gene Annotation of gene function requires a common terminology 6.2 ASSIGNING FUNCTION BY GENE INACTIVATION AND OVEREXPRESSION CHAPTER? EUKARYOTIC NUCLEAR GENOMES 153 131 131 131 132 133 134 135 Functional analysis by gene inactivation 136 Gene inactivation by genome editing 136 Gene inactivation by homologous recombination 137 Gene inactivation by transposon tagging and RNA interference 138 Gene overexpression can also be used to assess function 139 The phenotypic effect of gene inactivation or overexpression may be difficult to discern 140 6.3 UNDERSTANDING GENE FUNCTION BY STUDIES OF ITS EXPRESSION PATTERN AND PROTEIN PRODUCT 142 Reporter genes and immunocytochemistry can be used to locate where and when genes are expressed CRISPR can be used to make specific changes in a gene and the protein it encodes Other methods for site-directed mutagenesis PART 2 GENOME ANATOMIES 142 7.1 NUCLEAR GENOMES ARE CONTAINED IN CHROMOSOMES 153 Chromosomes are made of DNA and protein 153 The special features of metaphase chromosomes 155 Centromeres and telomeres have distinctive DNA sequences 157 7.2 THE GENETIC FEATURES OF NUCLEAR GENOMES 158 Gene numbers can be misleading
158 Genes are not evenly distributed within a genome 160 A segment of the human genome 161 The yeast genome is very compact 163 Gene organization in other eukaryotes 165 Families of genes 166 Pseudogenes and other evolutionary relics 167 7.3 THE REPETITIVE DNA CONTENT OF EUKARYOTIC NUCLEAR GENOMES 169 Tandemly repeated DNA is found at centromeres and elsewhere in eukaryotic chromosomes Minisatellites and microsatellites Interspersed repeats 169 170 171 SUMMARY 171 SHORT ANSWER QUESTIONS 172 IN-DEPTH PROBLEMS 173 FURTHER READING 173 143 145 6.4 USING CONVENTIONAL GENETIC ANALYSIS TO IDENTIFY GENE FUNCTION 147 Identification of human genes responsible for inherited diseases 147 Genome-wide association studies can also identify genes for diseases and other traits 149 SUMMARY 150 SHORT ANSWER QUESTIONS 151 CHAPTERS GENOMES OF PROKARYOTES AND EUKARYOTIC ORGANELLES 175 8.1 THE PHYSICAL FEATURES OF PROKARYOTIC GENOMES 175 The traditional view of the prokaryotic chromosome 175 Some bacteria have linear or multipartite genomes 177 8.2 THE GENETIC FEATURES OF PROKARYOTIC GENOMES 180
viii Contents Gene Organization in the E. coli K12 genome Operons are characteristic features of prokaryotic genomes Prokaryotic genome sizes and gene numbers vary according to biological complexity Genome sizes and gene numbers vary within individual species Distinctions between prokaryotic species are further blurred by horizontal gene transfer Metagenomes describe the members of a community 8.3 EUKARYOTIC ORGANELLE GENOMES The endosymbiont theory explains the origin of organelle genomes The physical and genetic features of organelle genomes 180 182 184 185 186 188 189 190 191 SUMMARY 195 SHORT ANSWER QUESTIONS 195 IN-DEPTH PROBLEMS 196 FURTHER READING 196 CHAPTER 9 VIRUS GENOMES AND MOBILE GENETIC ELEMENTS 199 9.1 THE GENOMES OF BACTERIOPHAGES AND EUKARYOTIC VIRUSES 199 Bacteriophage genomes have diverse structures and organizations 199 Replication strategies for bacteriophage genomes 201 Structures and replication strategies for eukaryotic viral genomes 202 CHAPTER 10 ACCESSING THE GENOME 10.1 INSIDETHE NUCLEUS The nucleus has an ordered internal structure Chromosomal DNA displays different degrees of packaging The nuclear matrix is a dynamic structure Each chromosome has its own territory within the nucleus Chromosomal DNA is organized into topologically associating domains Insulators prevent crosstalk between segments of chromosomal DNA 215 216 217 218 220 221 223 10.2 NUCLEOSOME MODIFICATIONS AND GENOME EXPRESSION 224 Acetylation of histones influences many nuclear activities, including genome expression Histone deacetylation represses active regions of the genome
Acetylation is not the only type of histone modification Nucleosome repositioning also influences gene expression 10.3 DNA MODIFICATION AND GENOME EXPRESSION Genome silencing by DNA methylation 225 226 227 230 231 231 Methylation is involved in genomic imprinting and X inactivation 232 234 SHORT ANSWER QUESTIONS 235 206 IN-DEPTH PROBLEMS 235 206 208 FURTHER READING 236 204 205 9.2 MOBILE GENETIC ELEMENTS 209 211 CHAPTER 11 THE ROLE OF DNA-BINDING PROTEINSINGENOME EXPRESSION 239 239 SUMMARY 212 SHORT ANSWER QUESTIONS 213 IN-DEPTH PROBLEMS 213 11.1 METHODS FOR STUDYING DNABINDING PROTEINS ANDTHEIR ATTACHMENT SITES 214 X-ray crystallography provides structural data for any protein that can be crystallized FURTHER READING 215 SUMMARY Some retroviruses cause cancer Genomes at the edge of life RNA transposons with long terminal repeats are related to viral retroelements Some RNA transposons lack LTRs DNA transposons are common in prokaryotic genomes DNA transposons are less common in eukaryotic genomes PART 3 HOW GENOMES ARE EXPRESSED 239
CONTENTS NMR spectroscopy is used to study the structures of small proteins Gel retardation identifies DNA fragments that bind to proteins Protection assays pinpoint binding sites with greater accuracy Modification interference identifies nucleotides central to protein binding Genome-wide scans for protein attachment sites 11.2 THE SPECIAL FEATURES OF DNA-BINDING PROTEINS The helix-turn-helix motif is present in prokaryotic and eukaryotic proteins Zinc fingers are common in eukaryotic proteins Other nucleic acid-binding motifs 11.3 THE INTERACTION BETWEEN DNA AND ITS BINDING PROTEINS 240 241 242 244 245 245 246 248 248 249 250 250 Contacts between DNA and proteins Direct readout of the nucleotide sequence The conformation of the helix also influences protein binding 251 SUMMARY 252 SHORT ANSWER QUESTIONS 253 IN-DEPTH PROBLEMS 253 FURTHER READING 254 CHAPTER 12 TRANSCRIPTOMES 257 12.1 THE COMPONENTS OFTHE TRANSCRIPTOME 257 The mRNA fraction of a transcriptome is small but complex 257 Short noncoding RNAs have diverse functions 258 Long noncoding RNAs are enigmatic transcripts 260 12.2 TRANSCRIPTOMICS: CATALOGING THE TRANSCRIPTOMES OF CELLS AND TISSUES Microarray analysis and RNA sequencing are used to study the contents of transcriptomes Single-cell studies add greater precision to transcriptomics Spatial transcriptomics enables transcripts to be mapped directly in tissues and cells 12.3 SYNTHESIS OFTHE COMPONENTS OF THE TRANSCRIPTOME RNA polymerases are molecular machines for making RNA Transcription start-points are indicated by promoter sequences Synthesis of bacterial
RNA is regulated by repressor and activator proteins Synthesis of bacterial RNA is also regulated by control over transcription termination Synthesis of eukaryotic RNA is regulated primarily by activator proteins 262 264 266 268 268 270 273 276 277 12.4 THE INFLUENCE OF RNA SPLICING ON THE COMPOSITION OF A TRANSCRIPTOME 280 The splicing pathway for eukaryotic pre-mRNA introns 281 The splicing process must have a high degree of precision 282 Enhancer and silencer elements specify alternative splicing pathways Backsplicing gives rise to circular RNAs 284 286 12.5 THE INFLUENCE OF CHEMICAL MODIFICATION ON THE COMPOSITION OF A TRANSCRIPTOME 287 RNA editing alters the coding properties of some transcripts 287 Chemical modifications that do not affect the sequence of an mRNA 289 12.6 DEGRADATION OFTHE COMPONENTS OF THE TRANSCRIPTOME 290 Several processes are known for nonspecific RNA turnover RNA silencing was first identified as a means of destroying invading viral RNA MicroRNAs regulate genome expression by causing specific target mRNAs tobe degraded 293 SUMMARY 294 SHORT ANSWER QUESTIONS 295 IN-DEPTH PROBLEMS 295 FURTHER READING 296 CHAPTER 13 PROTEOMES 262 ix 291 292 299 13.1 STUDYING THE COMPOSITION OF A PROTEOME 299 The separation stage of a protein profiling project 300 The identification stage of a protein profiling project 303 Comparing the compositions of two proteomes 305 Analytical protein arrays offer an alternative approach to protein profiling 306 13.2 IDENTIFYING PROTEINSTHAT INTERACT WITH ONE ANOTHER Identifying pairs of interacting proteins Identifying the
components of multiprotein complexes 307 307 309
x Contents Identifying proteins with functional interactions Protein interaction maps display the interactions within a proteome 311 311 13.3 SYNTHESIS AND DEGRADATION OF THE COMPONENTS OF THE PROTEOME 313 Ribosomes are molecular machines for making proteins 313 During stress, bacteria inactivate their ribosomes in order to downsize the proteome 316 Initiation factors mediate large-scale remodeling of eukaryotic proteomes 317 The translation of individual mRNAs can also be regulated 318 Degradation of the components of the proteome 320 14.2 CHANGES IN GENOME ACTIVITY RESULTING IN CELLULAR DIFFERENTIATION Some differentiation processes involve changes to chromatin structure Yeast mating types are determined by gene conversion events Genome rearrangements are responsible for immunoglobulin and T-cell receptor diversities 341 341 343 344 13.5 BEYOND THE PROTEOME The metabolome is the complete set of metabolites present in a cell Systems biology provides an integrated description of cellular activity 326 14.3 CHANGES IN GENOME ACTIVITY UNDERLYING DEVELOPMENT 346 Bacteriophage λ: a genetic switch enables a choice to be made between alternative developmental pathways 347 Bacillus sporulation: coordination of activities in two distinct cell types 348 Caenorhabditis elegans: the genetic basis to positional information and the determination of cell fate 351 Fruit flies: conversion of positional information into a segmented body plan 353 Homeotic selector genes are universal features of higher eukaryotic development 354 Homeotic genes also underlie plant development 356 327 SUMMARY
357 327 SHORT ANSWER QUESTIONS 358 SUMMARY 330 IN-DEPTH PROBLEMS 358 SHORT ANSWER QUESTIONS 331 FURTHER READING 359 IN-DEPTH PROBLEMS 332 FURTHER READING 332 13.4 THE INFLUENCE OF PROTEIN PROCESSING ON THE COMPOSITION OF THE PROTEOME / 320 The amino acid sequence contains instructions for protein folding 321 Some proteins undergo proteolytic cleavage 324 Important changes in protein activity can be brought about by chemical modification 325 CHAPTER 14 GENOME EXPRESSION IN THE CONTEXT OF CELL AND ORGANISM PART 4 HOW GENOMES REPLICATE AND EVOLVE CHAPTER 15 GENOME REPLICATION 335 14.1 THE RESPONSE OF THE GENOME TO EXTERNAL SIGNALS 335 Signal transmission by import of the extracellular signaling compound 336 Receptor proteins transmit signals across cell membranes 337 Some signal transduction pathways have few steps between receptor and genome 339 Some signal transduction pathways have many steps between receptor and genome 340 Some signal transduction pathways operate via second messengers 341 15.1 THE TOPOLOGY OF GENOME REPLICATION The double-helix structure complicates the replication process The Meselson-Stahl experiment proved that replication is semiconservative DNA topoisomerases provide a solution to the topological problem Variations on the semiconservative theme 15.2 THE INITIATION PHASE OF GENOME REPLICATION Initiation at the E. coli origin of replication 361 361 362 363 365 367 368 368
CONTENTS Origins of replication have been clearly defined in yeast 369 Origins in higher eukaryotes have been less easy to identify 370 15.3 EVENTS AT THE REPLICATION FORK 371 DNA polymerases are molecular machines for making (and degrading) DNA 371 DNA polymerases have limitations that complicate genome replication 373 Okazaki fragments must be joined together to complete lagging-strand replication 374 15.4 TERMINATION OF GENOME REPLICATION Replication of the E. coli genome terminates within a defined region 376 376 378 Completion of genome replication Telomerase completes replication of chromosomal DNA molecules, at least in some cells 380 Telomere length is implicated in cell senescence and cancer 382 Drosophila has a unique solution to the end shortening problem 383 15.5 REGULATION OF EUKARYOTIC GENOME REPLICATION 384 Genome replication must be synchronized with the cell cycle 384 Origin licensing is the prerequisite for passing the G1-S checkpoint 385 Replication origins do not all fire at the same time 386 The cell has various options if the genome is damaged 388 SUMMARY 388 SHORT ANSWER QUESTIONS 389 IN-DEPTH PROBLEMS 390 FURTHER READING 390 CHAPTER 16 RECOMBINATION AND TRANSPOSITION 16.1 HOMOLOGOUS RECOMBINATION The Holliday and Meselson-Radding models for homologous recombination The double-strand break model for homologous recombination RecBCD is the most important pathway for homologous recombination in bacteria E. coli has alternative pathways for homologous recombination 393 393 394 Homologous recombination pathways in eukaryotes 16.2 SITE-SPECIFIC
RECOMBINATION Bacteriophage λ uses site-specific recombination during the lysogenic infection cycle Site-specific recombination is an aid in construction of genetically modified plants 16.3 TRANSPOSITION Replicative and conservative transposition of DNA transposons Retroelements transpose replicati vely via an RNA intermediate xi 399 400 400 401 402 402 403 SUMMARY 405 SHORT ANSWER QUESTIONS 406 IN-DEPTH PROBLEMS 406 FURTHER READING 406 CHAPTER 17 MUTATIONS AND DNA REPAIR 17.1 THE CAUSES OF MUTATIONS Errors in replication are a source of point mutations Replication errors can also lead to insertion and deletion mutations Mutations are also caused by chemical and physical mutagens 17.2 REPAIR OF MUTATIONS AND OTHER TYPES OF DNA DAMAGE Direct repair systems fill in nicks and correct some types of nucleotide modification Base excision repairs many types of damaged nucleotide Nucleotide excision repair is used to correct more extensive types of damage Mismatch repair corrects replication errors Single- and double-strand breaks can be repaired Some types of damage can be repaired by homologous recombination If necessary, DNA damage can be bypassed during genome replication Defects in DNA repair underlie human diseases, including cancers 409 409 410 411 413 418 418 419 421 422 423 425 426 427 SUMMARY 427 396 SHORT ANSWER QUESTIONS 428 397 IN-DEPTH PROBLEMS 429 398 FURTHER READING 429
xii Contents CHAPTER 18 HOW GENOMES EVOLVE 431 18.1 GENOMES: THE FIRST 10 BILLION YEARS 431 The first biochemical systems were centered on RNA 431 The first DNA genomes 433 How unique is life? 434 18.2 THE EVOLUTION OF INCREASINGLY COMPLEX GENOMES Genome sequences provide extensive evidence of past gene duplications A variety of processes could result in gene duplication Whole-genome duplication is also possible Smaller duplications can also be identified in the human genome and other genomes Both prokaryotes and eukaryotes acquire genes from other species Genome evolution also involves rearrangement of existing gene sequences There are competing hypotheses for the origins of introns The evolution of the epigenome 436 436 439 440 443 444 18.3 GENOMES: THE LAST 6 MILLION YEARS The human genome is very similar to that of the chimpanzee Paleogenomics is helping us understand the recent evolution of the human genome 18.4 GENOMES TODAY: DIVERSITY IN POPULATIONS The origins of HIV/AIDS The first migrations of humans out of Africa The diversity of plant genomes is an aid in crop breeding 451 451 453 455 455 457 459 SUMMARY 460 SHORT ANSWER QUESTIONS 462 IN-DEPTH PROBLEMS 462 FURTHER READING 463 446 GLOSSARY 465 448 450 INDEX 509
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CONTENTS PREFACE ACKNOWLEDGEMENTS XIII XVII PARTI HOW GENOMES ARE STUDIED CHAPTER 1 GENOMES,TRANSCRIPTOMES, AND PROTEOMES 1.1 DNA Genes are made of DNA DNA is a polymer of nucleotides The discovery of the double helix The double helix is stabilized by base-pairing and base-stacking The double helix has structural flexibility 1.2 RNA AND THE TRANSCRIPTOME RNA is a second type of polynucleotide The RNA content of the cell Many RNAs are synthesized as precursor molecules There are different definitions of the transcriptome 1 2 3 5 б 8 9 11 11 12 13 15 1.3 PROTEINS ANDTHE PROTEOME 16 There are four hierarchical levels of protein structure 16 Amino acid diversity underlies protein diversity 16 The link between the transcriptome and the proteome 18 The genetic code is not universal 19 The link between the proteome and the biochemistry of the cell 20 SUMMARY 22 SHORT ANSWER QUESTIONS 23 IN-DEPTH PROBLEMS 23 FURTHER READING 24 CHAPTER 2 STUDYING DNA 25 2.1 ENZYMES FOR DNA MANIPULATION 26 The mode of action of a template-dependent DNA polymerase The types of DNA polymerase used in research Restriction endonucleases enable DNA molecules to be cut at defined positions Gel electrophoresis is used to examine the results of a restriction digest Interesting DNA fragments can be identified by Southern hybridization Ligases join DNA fragments together End-modification enzymes 2.2 THE POLYMERASE CHAINREACTION Carrying out a PGR The rate of product formation can be followed during a PGR PGR has many and diverse applications 2.3 DNA CLONING Why is gene cloning important? The simplest cloning
vectors are based on E. coli plasmids Bacteriophages can also be used as cloning vectors Vectors for longer pieces of DNA DNA can be cloned in organisms other than E. coli 26 28 29 32 33 34 35 35 36 37 38 38 39 39 41 44 45 SUMMARY 47 SHORT ANSWER QUESTIONS 48 IN-DEPTH PROBLEMS 48 FURTHER READING 49 CHAPTERS MAPPING GENOMES 51 3.1 WHY A GENOME MAP IS IMPORTANT Genome maps are needed in orderio sequence the more complex genomes Genome maps are not just sequencing aids 51 3.2 MARKERS FOR GENETIC MAPPING Genes were the first markers to be used RFLPs and SSLPs are examples of DNA markers Single-nucleotide polymorphisms are the most useful type of DNA marker 53 3.3 THE BASISTO GENETIC MAPPING 59 The principles of inheritance and the discovery of linkage 59 51 52 54 55 57
vi Contents Partial linkage is explained by the behavior of chromosomes during meiosis From partial linkage to genetic mapping 3.4 LINKAGE ANALYSIS WITH DIFFERENT TYPES OF ORGANISM Linkage analysis when planned breeding experiments are possible Gene mapping by human pedigree analysis Genetic mapping in bacteria The limitations of linkage analysis 3.5 PHYSICAL MAPPING BY DIRECT EXAMINATION OF DNA MOLECULES Conventional restriction mapping is only applicable to small DNA molecules Optical mapping can locate restriction sites in longer DNA molecules Optical mapping with fluorescent probes Further innovations extend the scope of optical mapping 3.6 PHYSICAL MAPPING BY ASSIGNING MARKERS TO DNA FRAGMENTS Any unique sequence can be used as an STS DNA fragments for STS mapping can be obtained as radiation hybrids A clone library can be used as the mapping reagent 60 63 64 64 66 67 69 Many prokaryotic genomes have been sequenced by the shotgun method Shotgun sequencing of eukaryotic genomes requires sophisticated assembly programs From contigs to scaffolds What is a'genome sequence'and do we always need one? 95 95 97 99 4.3 SEQUENCING THE HUMAN GENOME The Human Genome Project ֊ genome sequencing in the heroic age The human genome - genome sequencing in the modern age The Neanderthal genome - assembly of an extinct genome using the human sequence as a reference The human genome - new challenges 101 71 74 SUMMARY 108 SHORT ANSWER QUESTIONS 109 75 IN-DEPTH PROBLEMS 110 FURTHER READING 110 70 71 102 104 106 107 77 77 78 79 SUMMARY 80 SHORT ANSWER QUESTIONS 80 IN-DEPTH PROBLEMS 81
FURTHER READING 81 CHAPTER 4 SEQUENCING GENOMES 83 4.1 METHODOLOGY FOR DNA SEQUENCING Chain-termination sequencing of PCR products Illumina sequencing is the most popular short read method A variety of other short-read sequencing methods have been devised Single-molecule real-time sequencing provides reads up to 200 kb in length Nanopore sequencing is currently the longest long-read method 83 83 4.2 HOW TO SEQUENCE A GENOME The potential of the shotgun method was proven by the Haemophilus influenzae sequence 93 86 88 90 92 93 CHAPTER 5 GENOME ANNOTATION 113 5.1 GENOME ANNOTATION BY COMPUTER ANALYSIS OF THE DNA SEQUENCE 113 The coding regions of genes are open reading frames 113 Simple ORF scans are less effective with genomes of higher eukaryotes 114 Locating genes for noncoding RNA 116 Homology searches and comparative genomics give an extra dimension to gene prediction 117 5.2 GENOME ANNOTATION BY ANALYSIS OF GENE TRANSCRIPTS 119 Hybridization tests can determine if a fragment contains one or more genes 119 Methods are available for precise mapping of the ends of transcripts 120 Exon-intron boundaries can also be located with precision 121 5.3 ANNOTATION BY GENOME-WIDE RNA MAPPING 121 Tiling arrays enable transcripts to be mapped on to chromosomes or entire genomes 122 Transcript sequences can be directly mapped onto a genome 123 Obtaining transcript sequences by SAGE and CAGE 125
CONTENTS vii 5.4 GENOME BROWSERS 126 IN-DEPTH PROBLEMS 151 SUMMARY 128 FURTHER READING 152 SHORT ANSWER QUESTIONS 128 IN-DEPTH PROBLEMS 129 FURTHER READING 129 CHAPTER 6 IDENTIFYING GENE FUNCTIONS 6.1 COMPUTER ANALYSIS OF GENE FUNCTION Homology reflects evolutionary relationships Homology analysis can provide information on the function of a gene Identification of protein domains can help to assign function to an unknown gene Annotation of gene function requires a common terminology 6.2 ASSIGNING FUNCTION BY GENE INACTIVATION AND OVEREXPRESSION CHAPTER? EUKARYOTIC NUCLEAR GENOMES 153 131 131 131 132 133 134 135 Functional analysis by gene inactivation 136 Gene inactivation by genome editing 136 Gene inactivation by homologous recombination 137 Gene inactivation by transposon tagging and RNA interference 138 Gene overexpression can also be used to assess function 139 The phenotypic effect of gene inactivation or overexpression may be difficult to discern 140 6.3 UNDERSTANDING GENE FUNCTION BY STUDIES OF ITS EXPRESSION PATTERN AND PROTEIN PRODUCT 142 Reporter genes and immunocytochemistry can be used to locate where and when genes are expressed CRISPR can be used to make specific changes in a gene and the protein it encodes Other methods for site-directed mutagenesis PART 2 GENOME ANATOMIES 142 7.1 NUCLEAR GENOMES ARE CONTAINED IN CHROMOSOMES 153 Chromosomes are made of DNA and protein 153 The special features of metaphase chromosomes 155 Centromeres and telomeres have distinctive DNA sequences 157 7.2 THE GENETIC FEATURES OF NUCLEAR GENOMES 158 Gene numbers can be misleading
158 Genes are not evenly distributed within a genome 160 A segment of the human genome 161 The yeast genome is very compact 163 Gene organization in other eukaryotes 165 Families of genes 166 Pseudogenes and other evolutionary relics 167 7.3 THE REPETITIVE DNA CONTENT OF EUKARYOTIC NUCLEAR GENOMES 169 Tandemly repeated DNA is found at centromeres and elsewhere in eukaryotic chromosomes Minisatellites and microsatellites Interspersed repeats 169 170 171 SUMMARY 171 SHORT ANSWER QUESTIONS 172 IN-DEPTH PROBLEMS 173 FURTHER READING 173 143 145 6.4 USING CONVENTIONAL GENETIC ANALYSIS TO IDENTIFY GENE FUNCTION 147 Identification of human genes responsible for inherited diseases 147 Genome-wide association studies can also identify genes for diseases and other traits 149 SUMMARY 150 SHORT ANSWER QUESTIONS 151 CHAPTERS GENOMES OF PROKARYOTES AND EUKARYOTIC ORGANELLES 175 8.1 THE PHYSICAL FEATURES OF PROKARYOTIC GENOMES 175 The traditional view of the prokaryotic chromosome 175 Some bacteria have linear or multipartite genomes 177 8.2 THE GENETIC FEATURES OF PROKARYOTIC GENOMES 180
viii Contents Gene Organization in the E. coli K12 genome Operons are characteristic features of prokaryotic genomes Prokaryotic genome sizes and gene numbers vary according to biological complexity Genome sizes and gene numbers vary within individual species Distinctions between prokaryotic species are further blurred by horizontal gene transfer Metagenomes describe the members of a community 8.3 EUKARYOTIC ORGANELLE GENOMES The endosymbiont theory explains the origin of organelle genomes The physical and genetic features of organelle genomes 180 182 184 185 186 188 189 190 191 SUMMARY 195 SHORT ANSWER QUESTIONS 195 IN-DEPTH PROBLEMS 196 FURTHER READING 196 CHAPTER 9 VIRUS GENOMES AND MOBILE GENETIC ELEMENTS 199 9.1 THE GENOMES OF BACTERIOPHAGES AND EUKARYOTIC VIRUSES 199 Bacteriophage genomes have diverse structures and organizations 199 Replication strategies for bacteriophage genomes 201 Structures and replication strategies for eukaryotic viral genomes 202 CHAPTER 10 ACCESSING THE GENOME 10.1 INSIDETHE NUCLEUS The nucleus has an ordered internal structure Chromosomal DNA displays different degrees of packaging The nuclear matrix is a dynamic structure Each chromosome has its own territory within the nucleus Chromosomal DNA is organized into topologically associating domains Insulators prevent crosstalk between segments of chromosomal DNA 215 216 217 218 220 221 223 10.2 NUCLEOSOME MODIFICATIONS AND GENOME EXPRESSION 224 Acetylation of histones influences many nuclear activities, including genome expression Histone deacetylation represses active regions of the genome
Acetylation is not the only type of histone modification Nucleosome repositioning also influences gene expression 10.3 DNA MODIFICATION AND GENOME EXPRESSION Genome silencing by DNA methylation 225 226 227 230 231 231 Methylation is involved in genomic imprinting and X inactivation 232 234 SHORT ANSWER QUESTIONS 235 206 IN-DEPTH PROBLEMS 235 206 208 FURTHER READING 236 204 205 9.2 MOBILE GENETIC ELEMENTS 209 211 CHAPTER 11 THE ROLE OF DNA-BINDING PROTEINSINGENOME EXPRESSION 239 239 SUMMARY 212 SHORT ANSWER QUESTIONS 213 IN-DEPTH PROBLEMS 213 11.1 METHODS FOR STUDYING DNABINDING PROTEINS ANDTHEIR ATTACHMENT SITES 214 X-ray crystallography provides structural data for any protein that can be crystallized FURTHER READING 215 SUMMARY Some retroviruses cause cancer Genomes at the edge of life RNA transposons with long terminal repeats are related to viral retroelements Some RNA transposons lack LTRs DNA transposons are common in prokaryotic genomes DNA transposons are less common in eukaryotic genomes PART 3 HOW GENOMES ARE EXPRESSED 239
CONTENTS NMR spectroscopy is used to study the structures of small proteins Gel retardation identifies DNA fragments that bind to proteins Protection assays pinpoint binding sites with greater accuracy Modification interference identifies nucleotides central to protein binding Genome-wide scans for protein attachment sites 11.2 THE SPECIAL FEATURES OF DNA-BINDING PROTEINS The helix-turn-helix motif is present in prokaryotic and eukaryotic proteins Zinc fingers are common in eukaryotic proteins Other nucleic acid-binding motifs 11.3 THE INTERACTION BETWEEN DNA AND ITS BINDING PROTEINS 240 241 242 244 245 245 246 248 248 249 250 250 Contacts between DNA and proteins Direct readout of the nucleotide sequence The conformation of the helix also influences protein binding 251 SUMMARY 252 SHORT ANSWER QUESTIONS 253 IN-DEPTH PROBLEMS 253 FURTHER READING 254 CHAPTER 12 TRANSCRIPTOMES 257 12.1 THE COMPONENTS OFTHE TRANSCRIPTOME 257 The mRNA fraction of a transcriptome is small but complex 257 Short noncoding RNAs have diverse functions 258 Long noncoding RNAs are enigmatic transcripts 260 12.2 TRANSCRIPTOMICS: CATALOGING THE TRANSCRIPTOMES OF CELLS AND TISSUES Microarray analysis and RNA sequencing are used to study the contents of transcriptomes Single-cell studies add greater precision to transcriptomics Spatial transcriptomics enables transcripts to be mapped directly in tissues and cells 12.3 SYNTHESIS OFTHE COMPONENTS OF THE TRANSCRIPTOME RNA polymerases are molecular machines for making RNA Transcription start-points are indicated by promoter sequences Synthesis of bacterial
RNA is regulated by repressor and activator proteins Synthesis of bacterial RNA is also regulated by control over transcription termination Synthesis of eukaryotic RNA is regulated primarily by activator proteins 262 264 266 268 268 270 273 276 277 12.4 THE INFLUENCE OF RNA SPLICING ON THE COMPOSITION OF A TRANSCRIPTOME 280 The splicing pathway for eukaryotic pre-mRNA introns 281 The splicing process must have a high degree of precision 282 Enhancer and silencer elements specify alternative splicing pathways Backsplicing gives rise to circular RNAs 284 286 12.5 THE INFLUENCE OF CHEMICAL MODIFICATION ON THE COMPOSITION OF A TRANSCRIPTOME 287 RNA editing alters the coding properties of some transcripts 287 Chemical modifications that do not affect the sequence of an mRNA 289 12.6 DEGRADATION OFTHE COMPONENTS OF THE TRANSCRIPTOME 290 Several processes are known for nonspecific RNA turnover RNA silencing was first identified as a means of destroying invading viral RNA MicroRNAs regulate genome expression by causing specific target mRNAs tobe degraded 293 SUMMARY 294 SHORT ANSWER QUESTIONS 295 IN-DEPTH PROBLEMS 295 FURTHER READING 296 CHAPTER 13 PROTEOMES 262 ix 291 292 299 13.1 STUDYING THE COMPOSITION OF A PROTEOME 299 The separation stage of a protein profiling project 300 The identification stage of a protein profiling project 303 Comparing the compositions of two proteomes 305 Analytical protein arrays offer an alternative approach to protein profiling 306 13.2 IDENTIFYING PROTEINSTHAT INTERACT WITH ONE ANOTHER Identifying pairs of interacting proteins Identifying the
components of multiprotein complexes 307 307 309
x Contents Identifying proteins with functional interactions Protein interaction maps display the interactions within a proteome 311 311 13.3 SYNTHESIS AND DEGRADATION OF THE COMPONENTS OF THE PROTEOME 313 Ribosomes are molecular machines for making proteins 313 During stress, bacteria inactivate their ribosomes in order to downsize the proteome 316 Initiation factors mediate large-scale remodeling of eukaryotic proteomes 317 The translation of individual mRNAs can also be regulated 318 Degradation of the components of the proteome 320 14.2 CHANGES IN GENOME ACTIVITY RESULTING IN CELLULAR DIFFERENTIATION Some differentiation processes involve changes to chromatin structure Yeast mating types are determined by gene conversion events Genome rearrangements are responsible for immunoglobulin and T-cell receptor diversities 341 341 343 344 13.5 BEYOND THE PROTEOME The metabolome is the complete set of metabolites present in a cell Systems biology provides an integrated description of cellular activity 326 14.3 CHANGES IN GENOME ACTIVITY UNDERLYING DEVELOPMENT 346 Bacteriophage λ: a genetic switch enables a choice to be made between alternative developmental pathways 347 Bacillus sporulation: coordination of activities in two distinct cell types 348 Caenorhabditis elegans: the genetic basis to positional information and the determination of cell fate 351 Fruit flies: conversion of positional information into a segmented body plan 353 Homeotic selector genes are universal features of higher eukaryotic development 354 Homeotic genes also underlie plant development 356 327 SUMMARY
357 327 SHORT ANSWER QUESTIONS 358 SUMMARY 330 IN-DEPTH PROBLEMS 358 SHORT ANSWER QUESTIONS 331 FURTHER READING 359 IN-DEPTH PROBLEMS 332 FURTHER READING 332 13.4 THE INFLUENCE OF PROTEIN PROCESSING ON THE COMPOSITION OF THE PROTEOME / 320 The amino acid sequence contains instructions for protein folding 321 Some proteins undergo proteolytic cleavage 324 Important changes in protein activity can be brought about by chemical modification 325 CHAPTER 14 GENOME EXPRESSION IN THE CONTEXT OF CELL AND ORGANISM PART 4 HOW GENOMES REPLICATE AND EVOLVE CHAPTER 15 GENOME REPLICATION 335 14.1 THE RESPONSE OF THE GENOME TO EXTERNAL SIGNALS 335 Signal transmission by import of the extracellular signaling compound 336 Receptor proteins transmit signals across cell membranes 337 Some signal transduction pathways have few steps between receptor and genome 339 Some signal transduction pathways have many steps between receptor and genome 340 Some signal transduction pathways operate via second messengers 341 15.1 THE TOPOLOGY OF GENOME REPLICATION The double-helix structure complicates the replication process The Meselson-Stahl experiment proved that replication is semiconservative DNA topoisomerases provide a solution to the topological problem Variations on the semiconservative theme 15.2 THE INITIATION PHASE OF GENOME REPLICATION Initiation at the E. coli origin of replication 361 361 362 363 365 367 368 368
CONTENTS Origins of replication have been clearly defined in yeast 369 Origins in higher eukaryotes have been less easy to identify 370 15.3 EVENTS AT THE REPLICATION FORK 371 DNA polymerases are molecular machines for making (and degrading) DNA 371 DNA polymerases have limitations that complicate genome replication 373 Okazaki fragments must be joined together to complete lagging-strand replication 374 15.4 TERMINATION OF GENOME REPLICATION Replication of the E. coli genome terminates within a defined region 376 376 378 Completion of genome replication Telomerase completes replication of chromosomal DNA molecules, at least in some cells 380 Telomere length is implicated in cell senescence and cancer 382 Drosophila has a unique solution to the end shortening problem 383 15.5 REGULATION OF EUKARYOTIC GENOME REPLICATION 384 Genome replication must be synchronized with the cell cycle 384 Origin licensing is the prerequisite for passing the G1-S checkpoint 385 Replication origins do not all fire at the same time 386 The cell has various options if the genome is damaged 388 SUMMARY 388 SHORT ANSWER QUESTIONS 389 IN-DEPTH PROBLEMS 390 FURTHER READING 390 CHAPTER 16 RECOMBINATION AND TRANSPOSITION 16.1 HOMOLOGOUS RECOMBINATION The Holliday and Meselson-Radding models for homologous recombination The double-strand break model for homologous recombination RecBCD is the most important pathway for homologous recombination in bacteria E. coli has alternative pathways for homologous recombination 393 393 394 Homologous recombination pathways in eukaryotes 16.2 SITE-SPECIFIC
RECOMBINATION Bacteriophage λ uses site-specific recombination during the lysogenic infection cycle Site-specific recombination is an aid in construction of genetically modified plants 16.3 TRANSPOSITION Replicative and conservative transposition of DNA transposons Retroelements transpose replicati vely via an RNA intermediate xi 399 400 400 401 402 402 403 SUMMARY 405 SHORT ANSWER QUESTIONS 406 IN-DEPTH PROBLEMS 406 FURTHER READING 406 CHAPTER 17 MUTATIONS AND DNA REPAIR 17.1 THE CAUSES OF MUTATIONS Errors in replication are a source of point mutations Replication errors can also lead to insertion and deletion mutations Mutations are also caused by chemical and physical mutagens 17.2 REPAIR OF MUTATIONS AND OTHER TYPES OF DNA DAMAGE Direct repair systems fill in nicks and correct some types of nucleotide modification Base excision repairs many types of damaged nucleotide Nucleotide excision repair is used to correct more extensive types of damage Mismatch repair corrects replication errors Single- and double-strand breaks can be repaired Some types of damage can be repaired by homologous recombination If necessary, DNA damage can be bypassed during genome replication Defects in DNA repair underlie human diseases, including cancers 409 409 410 411 413 418 418 419 421 422 423 425 426 427 SUMMARY 427 396 SHORT ANSWER QUESTIONS 428 397 IN-DEPTH PROBLEMS 429 398 FURTHER READING 429
xii Contents CHAPTER 18 HOW GENOMES EVOLVE 431 18.1 GENOMES: THE FIRST 10 BILLION YEARS 431 The first biochemical systems were centered on RNA 431 The first DNA genomes 433 How unique is life? 434 18.2 THE EVOLUTION OF INCREASINGLY COMPLEX GENOMES Genome sequences provide extensive evidence of past gene duplications A variety of processes could result in gene duplication Whole-genome duplication is also possible Smaller duplications can also be identified in the human genome and other genomes Both prokaryotes and eukaryotes acquire genes from other species Genome evolution also involves rearrangement of existing gene sequences There are competing hypotheses for the origins of introns The evolution of the epigenome 436 436 439 440 443 444 18.3 GENOMES: THE LAST 6 MILLION YEARS The human genome is very similar to that of the chimpanzee Paleogenomics is helping us understand the recent evolution of the human genome 18.4 GENOMES TODAY: DIVERSITY IN POPULATIONS The origins of HIV/AIDS The first migrations of humans out of Africa The diversity of plant genomes is an aid in crop breeding 451 451 453 455 455 457 459 SUMMARY 460 SHORT ANSWER QUESTIONS 462 IN-DEPTH PROBLEMS 462 FURTHER READING 463 446 GLOSSARY 465 448 450 INDEX 509 |
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| spelling | Brown, Terence A. 1953- Verfasser (DE-588)113251661 aut Genomes Genomes 5 T.A. Brown Fifth edition Boca Raton ; London ; New York CRC Press, Taylor & Francis Group 2023 xv, 530 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Genom (DE-588)4156640-3 gnd rswk-swf Genetik (DE-588)4071711-2 gnd rswk-swf Molekulargenetik (DE-588)4039987-4 gnd rswk-swf (DE-588)4151278-9 Einführung gnd-content (DE-588)4123623-3 Lehrbuch gnd-content Genom (DE-588)4156640-3 s DE-604 Molekulargenetik (DE-588)4039987-4 s Genetik (DE-588)4071711-2 s Erscheint auch als Online-Ausgabe 978-1-003-13316-2 Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034222709&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Brown, Terence A. 1953- Genomes 5 Genom (DE-588)4156640-3 gnd Genetik (DE-588)4071711-2 gnd Molekulargenetik (DE-588)4039987-4 gnd |
| subject_GND | (DE-588)4156640-3 (DE-588)4071711-2 (DE-588)4039987-4 (DE-588)4151278-9 (DE-588)4123623-3 |
| title | Genomes 5 |
| title_alt | Genomes |
| title_auth | Genomes 5 |
| title_exact_search | Genomes 5 |
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| title_full | Genomes 5 T.A. Brown |
| title_fullStr | Genomes 5 T.A. Brown |
| title_full_unstemmed | Genomes 5 T.A. Brown |
| title_short | Genomes 5 |
| title_sort | genomes 5 |
| topic | Genom (DE-588)4156640-3 gnd Genetik (DE-588)4071711-2 gnd Molekulargenetik (DE-588)4039987-4 gnd |
| topic_facet | Genom Genetik Molekulargenetik Einführung Lehrbuch |
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