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BK

First edition

Boca Raton ; London ; New York : CRC Press, Taylor & Francis Group, 2023

xv, 530 stran : ilustrace (převážně barevné) ; 28 cm

ISBN 978-0-367-67407-6 (brožováno)

Garland science book

Terminologický slovník

Obsahuje bibliografie a rejstřík

002002019

PREFACE XIII // ACKNOWLEDGEMENTS XVII // PART I HOW GENOMES ARE STUDIED // CHAPTER 1 GENOMES, TRANSCRIPTOMES, AND PROTEOMES 1 // 1.1 DNA 2 // Genes are made of DNA 3 // DNA is a polymer of nucleotides 5 // The discovery of the double helix 6 // The double helix is stabilized by base-pairing and base-stacking 8 // The double helix has structural flexibility 9 // 1.2 RNA ANDTHETRANSCRIPTOME 11 // RNA is a second type of polynucleotide 11 // The RNA content of the cell 12 // Many RNAs are synthesized as precursor molecules 13 // There are different definitions of the transcriptome 15 // 1.3 PROTEINS AND THE 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 26 // The types of DNA polymerase used in research 28 // Restriction endonucleases enable DNA molecules to be cut at defined positions 29 // Gel electrophoresis is used to examine the results of a restriction digest 32 // Interesting DNA fragments can be identified by Southern hybridization 33 // Ligases join DNA fragments together 34 // End-modification enzymes 35 // 2.2 THE POLYMERASE CHAIN REACTION 35 // Carrying out a PCR 36 // The rate of product formation can be followed during a PCR 37 // PCR has many and diverse applications 38 // 2.3 DNA CLONING 38 // Why is gene cloning important? 39 // The simplest cloning vectors are based on E. coli plasmids 39 // Bacteriophages can also be used as cloning vectors 41 // Vectors for longer pieces of DNA 44 // DNA can be cloned in organisms other than E. coli 45 // SUMMARY 47 // SHORT ANSWER QUESTIONS 48 //

IN-DEPTH PROBLEMS 48 // FURTHER READING 49 // CHAPTER 3 MAPPING GENOMES 51 // 3.1 WHY A GENOME MAP IS IMPORTANT 51 // Genome maps are needed in order to sequence the more complex genomes 51 // Genome maps are not just sequencing aids 52 // 3.2 MARKERS FOR GENETIC MAPPING 53 // Genes were the first markers to be used 54 // RFLPs and SSLPs are examples of DNA markers 55 // Single-nucleotide polymorphisms are the most useful type of DNA marker 57 // 3.3 THE BASIS TO GENETIC MAPPING 59 // The principles of inheritance and the discovery of linkage 59 // Partial linkage is explained by the behavior of chromosomes during meiosis 60 // From partial linkage to genetic mapping 63 // 3.4 LINKAGE ANALYSIS WITH DIFFERENT TYPES OF ORGANISM 64 // Linkage analysis when planned breeding experiments are possible 64 // Gene mapping by human pedigree analysis 66 // Genetic mapping in bacteria 67 // The limitations of linkage analysis 69 // 3.5 PHYSICAL MAPPING BY DIRECT EXAMINATION OF DNA MOLECULES 70 // Conventional restriction mapping is only applicable to small DNA molecules 71 // Optical mapping can locate restriction sites in longer DNA molecules 71 // Optical mapping with fluorescent probes 74 // Further innovations extend the scope of optical mapping 75 // 3.6 PHYSICAL MAPPING BY ASSIGNING MARKERS TO DNA FRAGMENTS 77 // Any unique sequence can be used as an STS 77 // DNA fragments for STS mapping can be obtained as radiation hybrids 78 // A clone library can be used as the mapping reagent 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 83 // Chain-termination sequencing of PCR products 83 // Illumina sequencing is the most popular short-read method 86 // A variety of other short-read sequencing methods have been devised 88 // Single-molecule real-time sequencing provides reads up to 200 kb in length 90 //

Nanopore sequencing is currently the longest long-read method 92 // 4.2 HOWTO SEQUENCE A GENOME 93 // The potential of the shotgun method was proven by the Haemophilus influenzae sequence 93 // Many prokaryotic genomes have been sequenced by the shotgun method 95 // Shotgun sequencing of eukaryotic genomes requires sophisticated assembly programs 95 // From contigs to scaffolds 97 // What is a ’genome sequence’ and do we always need one? 99 // 4.3 SEQUENCINGTHE HUMAN GENOME 101 // The Human Genome Project - genome sequencing in the heroic age 102 // The human genome - genome sequencing in the modern age 104 // The Neanderthal genome - assembly of an extinct genome using the human sequence as a reference 106 // The human genome - new challenges 107 // SUMMARY 108 // SHORT ANSWER QUESTIONS 109 // IN-DEPTH PROBLEMS 110 // FURTHER READING 110 // CHAPTER 5 GENOME ANNOTATION 113 // 5.1 GENOME ANNOTATION BY COMPUTER ANALYSIS OFTHE 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 // 5.4 GENOME BROWSERS 126 // SUMMARY 128 // SHORT ANSWER QUESTIONS 128 // IN-DEPTH PROBLEMS 129 // FURTHER READING 129 // CHAPTER 6 IDENTIFYING GENE FUNCTIONS 131 // 6.1 COMPUTER ANALYSIS OF GENE FUNCTION 131 //

Homology reflects evolutionary relationships 131 // Homology analysis can provide information on the function of a gene 132 // Identification of protein domains can help to assign function to an unknown gene 133 // Annotation of gene function requires a common terminology 134 // 6.2 ASSIGNING FUNCTION BY GENE INACTIVATION AND OVEREXPRESSION 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 142 // CRISPR can be used to make specific changes in a gene and the protein it encodes 143 // Other methods for site-directed mutagenesis 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 // IN-DEPTH PROBLEMS 151 // FURTHER READING 152 // PART 2 GENOME ANATOMIES // CHAPTER 7 EUKARYOTIC NUCLEAR GENOMES 153 // 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 169 // Minisatellites and microsatellites 170 // Interspersed repeats 171 // SUMMARY 171 // SHORT ANSWER QUESTIONS 172 // IN-DEPTH PROBLEMS 173 // FURTHER READING 173 // CHAPTER 8 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 // Gene organization in the E. coli K12 genome 180 // Operons are characteristic features of prokaryotic genomes 182 // Prokaryotic genome sizes and gene numbers vary according to biological complexity 184 // Genome sizes and gene numbers vary within individual species 185 // Distinctions between prokaryotic species are further blurred by horizontal gene transfer 186 // Metagenomes describe the members of a community 188 // 8.3 EUKARYOTIC ORGANELLE GENOMES 189 // The endosymbiont theory explains the origin of organelle genomes 190 // The physical and genetic features of organelle genomes 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 // Some retroviruses cause cancer 204 // Genomes at the edge of life 205 // 9.2 MOBILE GENETIC ELEMENTS 206 // RNA transposons with long terminal repeats are related to viral retroelements 206 // Some RNA transposons lack LTRs 208 //

DNA transposons are common in prokaryotic genomes 209 // DNA transposons are less common in eukaryotic genomes 211 // SUMMARY 212 // SHORT ANSWER QUESTIONS 213 // IN-DEPTH PROBLEMS 213 // FURTHER READING 214 // PART 3 HOW GENOMES ARE EXPRESSED // CHAPTER 10 ACCESSING THE GENOME 215 // 10.1 INSIDETHE NUCLEUS 215 // The nucleus has an ordered internal structure 216 // Chromosomal DNA displays different degrees of packaging 217 // The nuclear matrix is a dynamic structure 218 // Each chromosome has its own territory within the nucleus 220 // Chromosomal DNA is organized into topologically associating domains 221 // Insulators prevent crosstalk between segments of chromosomal DNA 223 // 10.2 NUCLEOSOME MODIFICATIONS AND GENOME EXPRESSION 224 // Acetylation of histones influences many nuclear activities, including genome expression 225 // Histone deacetylation represses active regions of the genome 226 // Acetylation is not the only type of histone modification 227 // Nucleosome repositioning also influences gene expression 230 // 10.3 DNA MODIFICATION AND GENOME EXPRESSION 231 // Genome silencing by DNA methylation 231 // Methylation is involved in genomic imprinting and X inactivation 232 // SUMMARY 234 // SHORT ANSWER QUESTIONS 235 // IN-DEPTH PROBLEMS 235 // FURTHER READING 236 // CHAPTER 11 THE ROLE OF DNA-BINDING PROTEINS IN GENOME EXPRESSION 239 // 11.1 METHODS FOR STUDYING DNA-BINDING PROTEINS ANDTHEIR ATTACHMENT SITES 239 // X-ray crystallography provides structural data for any protein that can be crystallized 239 // NMR spectroscopy is used to study the structures of small proteins 240 // Gel retardation identifies DNA fragments that bind to proteins 241 // Protection assays pinpoint binding sites with greater accuracy 242 // Modification interference identifies nucleotides central to protein binding 244 // Genome-wide scans for protein attachment sites 245 //

11.2 THE SPECIAL FEATURES OF DNA-BINDING PROTEINS 245 // The helix-turn-helix motif is present in prokaryotic and eukaryotic proteins 246 // Zinc fingers are common in eukaryotic proteins 248 // Other nucleic acid-binding motifs 248 // 11.3 THE INTERACTION BETWEEN DNA AND ITS BINDING PROTEINS 249 // Contacts between DNA and proteins 250 // Direct readout of the nucleotide sequence 250 // 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 OF THE 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 262 // Microarray analysis and RNA sequencing are used to study the contents of transcriptomes 262 // Single-cell studies add greater precision to transcriptomics 264 // Spatial transcriptomics enables transcripts to be mapped directly in tissues and cells 266 // 12.3 SYNTHESIS OF THE COMPONENTS OF THE TRANSCRIPTOME 268 // RNA polymerases are molecular machines for making RNA 268 // Transcription start-points are indicated by promoter sequences 270 // Synthesis of bacterial RNA is regulated by repressor and activator proteins 273 // Synthesis of bacterial RNA is also regulated by control over transcription termination 276 // Synthesis of eukaryotic RNA is regulated primarily by activator proteins 277 // 12.4THE 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 284 // Backsplicing gives rise to circular RNAs 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 OF THE COMPONENTS OF THE TRANSCRIPTOME 290 // Several processes are known for nonspecific RNA turnover 291 // RNA silencing was first identified as a means of destroying invading viral RNA 292 // MicroRNAs regulate genome expression by causing specific target mRNAs to be degraded 293 // SUMMARY 294 // SHORT ANSWER QUESTIONS 295 // IN-DEPTH PROBLEMS 295 // FURTHER READING 296 // CHAPTER 13 PROTEOMES 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 PROTEINS THAT INTERACT WITH ONE ANOTHER 307 // Identifying pairs of interacting proteins 307 // Identifying the components of multiprotein complexes 309 // Identifying proteins with functional interactions 311 // Protein interaction maps display the interactions within a proteome 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 // 13.4THE 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 //

13.5 BEYOND THE PROTEOME 326 // The metabolome is the complete set of metabolites present in a cell 327 // Systems biology provides an integrated description of cellular activity 327 // SUMMARY 330 // SHORT ANSWER QUESTIONS 331 // IN-DEPTH PROBLEMS 332 // FURTHER READING 332 // CHAPTER 14 GENOME EXPRESSION IN THE CONTEXT OF CELL AND ORGANISM 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 // 14.2 CHANGES IN GENOMEACTIVITY RESULTING IN CELLULAR DIFFERENTIATION 341 // Some differentiation processes involve changes to chromatin structure 341 // Yeast mating types are determined by gene conversion events 343 // Genome rearrangements are responsible for immunoglobulin and T-cell receptor diversities 344 // 14.3 CHANGES IN GENOME ACTIVITY UNDERLYING DEVELOPMENT 346 // Bacteriophage X: 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 // SUMMARY 357 // SHORT ANSWER QUESTIONS 358 // IN-DEPTH PROBLEMS 358 // FURTHER READING 359 // PART 4 HOW GENOMES REPLICATE AND EVOLVE // CHAPTER 15 GENOME REPLICATION 361 // 15.1 THETOPOLOGY OF GENOME REPLICATION 361 //

The double-helix structure complicates the replication process 362 // The Meselson-Stahl experiment proved that replication is semiconservative 363 // DNA topoisomerases provide a solution to the topological problem 365 // Variations on the semiconservative theme 367 // 15.2 THE INITIATION PHASE OF GENOME REPLICATION 368 // Initiation at the E. coli origin of replication 368 // 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 // 15.4TERMINATION OF GENOME REPLICATION 376 // Replication of the E. coli genome terminates within a defined region 376 // Completion of genome replication 378 // 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 393 // 16.1 HOMOLOGOUS RECOMBINATION 393 // The Holliday and Meselson-Radding models for homologous recombination 394 // The double-strand break model for homologous recombination 396 // RecBCD is the most important pathway for homologous recombination in bacteria 397 // £ coli has alternative pathways for homologous recombination 398 //

Homologous recombination pathways in eukaryotes 399 // 16.2 SITE-SPECIFIC RECOMBINATION 400 // Bacteriophage K uses site-specific recombination during the lysogenic infection cycle 400 // Site-specific recombination is an aid in construction of genetically modified plants 401 // 16.3 TRANSPOSITION 402 // Replicative and conservative transposition of DNA transposons 402 // Retroelements transpose replicatively via an RNA intermediate 403 // SUMMARY 405 // SHORT ANSWER QUESTIONS 406 // IN-DEPTH PROBLEMS 406 // FURTHER READING 406 // CHAPTER 17 // MUTATIONS AND DNA REPAIR 409 // 17.1 THE CAUSES OF MUTATIONS 409 // Errors in replication are a source of point mutations 410 // Replication errors can also lead to insertion and deletion mutations 411 // Mutations are also caused by chemical and physical mutagens 413 // 17.2 REPAIR OF MUTATIONS AND OTHER TYPES OF DNA DAMAGE 418 // Direct repair systems fill in nicks and correct some types of nucleotide modification 418 // Base excision repairs many types of damaged nucleotide 419 // Nucleotide excision repair is used to correct more extensive types of damage 421 // Mismatch repair corrects replication errors 422 // Single- and double-strand breaks can be repaired 423 // Some types of damage can be repaired by homologous recombination 425 // If necessary, DNA damage can be bypassed during genome replication 426 // Defects in DNA repair underlie human diseases, including cancers 427 // SUMMARY 427 // SHORT ANSWER QUESTIONS 428 // IN-DEPTH PROBLEMS 429 // FURTHER READING 429 // 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 436 // Genome sequences provide extensive evidence of past gene duplications 436 //

A variety of processes could result in gene duplication 439 // Whole-genome duplication is also possible 440 // Smaller duplications can also be identified in the human genome and other genomes 443 // Both prokaryotes and eukaryotes acquire genes from other species 444 // Genome evolution also involves rearrangement of existing gene sequences 446 // There are competing hypotheses for the origins of introns 448 // The evolution of the epigenome 450 // 18.3 GENOMES: THE LAST 6 MILLION YEARS 451 // The human genome is very similar to that of the chimpanzee 451 // Paleogenomics is helping us understand the recent evolution of the human genome 453 // 18.4 GENOMES TODAY: DIVERSITY IN POPULATIONS 455 // The origins of HIV/AIDS 455 // The first migrations of humans out of Africa 457 // The diversity of plant genomes is an aid in crop breeding 459 // SUMMARY 460 // SHORT ANSWER QUESTIONS 462 // IN-DEPTH PROBLEMS 462 // FURTHER READING 463 // GLOSSARY 465 // INDEX 509