The genome of a living being is composed of DNA sequences with diverse origins. Beyond single-copy genes, whose product has a biological function that can be inferred by experimentation, certain DNA sequences, present in a large number of copies, escape the most refined approaches aimed at elucidating their precise role.
The existence of what 20th century geneticists had already perceived (and wrongly described as "junk DNA"!) was confirmed by the sequencing of the first complex genomes, including that of Homo sapiens. A large part of what defines a living thing is not unique, but repeated, sometimes a very large number of times, increasing in complexity with successive duplications and multiplication.
Understanding and defining the many functions of this myriad of repeated sequences, as well as their evolution through natural selection, has become one of the major challenges for 21st century genomics.
Table of Contents
Foreword xiii
Bernard DUJON
Introduction xv
Guy-Franck RICHARD
Chapter 1 Whole-Genome Duplications, a Source of Redundancy at the Entire-Genome Scale 1
Elise PAREY and Camille BERTHELOT
1.1 Prevalence of polyploids in the tree of life 2
1.1.1 Whole duplications in eukaryotes 2
1.1.2 Polyploidies in prokaryotic organisms 6
1.1.3 Polyploid cells in normal and pathological physiology 7
1.2 Mechanisms for the appearance of whole-genome duplications 7
1.2.1 Non-separation of chromosomes after replication 7
1.2.2 Autopolyploidization, a perfect genome redundancy 9
1.2.3 Allopolyploidization, an overlapping of genomes of similar species 9
1.3 Cellular consequences of whole-genome duplications 11
1.3.1 Disruption of cell and nucleus organization 11
1.3.2 Modifications in the expression of genes and transposons 13
1.3.3 Unstable meiosis 15
1.4 Rediploidization: evolutionary reduction in genetic redundancy 16
1.4.1 Resolution of meiosis by karyotype rearrangement 16
1.4.2 Evolutionary divergence of duplicated sequences 18
1.4.3 Bias and dominance during rediploidization 20
1.4.4 Incomplete and lineage-specific rediploidizations 21
1.5 Functions and evolution of duplicated genes 22
1.5.1 Redundancy and subfunctionalization 23
1.5.2 Neofunctionalization and evolutionary innovations 24
1.5.3 Gene repertoire bias 26
1.5.4 Regulatory blocks and splitting of regulatory regions 29
1.6 Whole-genome duplications and evolutionary diversification 32
1.6.1 Association with geological crises 32
1.6.2 Evolutionary speciations and radiations 33
1.7 Perspectives and conclusions 34
1.8 References 35
Chapter 2 Segmental Duplications and CNVs: Adaptive Potential of Structural Polymorphism 47
Patricia BALARESQUE and Franklin DELEHELLE
2.1 The multiple facets of genetic polymorphism 48
2.2 From Segmental Duplications to Copy Number Variants: terminology 49
2.3 SDs: a general overview 49
2.3.1 Background 49
2.3.2 SDs: more than a category of sequences, superstructures 50
2.3.3 SD and CNV: study biases related to the attractiveness of subjects as well as to the technological developments of the moment 51
2.3.4 SD: characteristics in human and non-human primates 52
2.4 Methodologies for detecting structural variation in genomes 53
2.4.1 In vitro methods 54
2.4.2 Methods on reads 54
2.4.3 Post-assembly methods 54
2.5 The molecular mechanisms at the origin of structural variation 56
2.5.1 Homologous recombination mechanisms 56
2.5.2 Non-homologous recombination mechanisms 57
2.6 Regions rich in SDs/LCRs favor the creation of CNVs: insertions/duplications, deletions and inversions 58
2.6.1 Insertions/duplications and deletions 58
2.6.2 Inversions 60
2.7 From SDs to CNVs in humans and primates 61
2.7.1 General overview 61
2.7.2 Delineating regions of interest 61
2.7.3 Heterogeneity in the distribution of intra- and interchromosomal SDs 62
2.7.4 Intrachromosomal and interchromosomal SDs: what do they teach us about the evolutionary history and origin of SDs? 62
2.7.5 Intra- and interchromosomal SDs: the specific case of sex chromosomes 66
2.7.6 SDs: an association with specific sequences? 66
2.8 SDs in little-studied species: general genomic profiles 66
2.8.1 Twelve genomes under study 68
2.8.2 Distribution and characteristics of SDs in genomes 70
2.9 SD content: impact of a duplicated environment on sequences that make up the SDs 70
2.9.1 SDs and non-coding sequences: the case of microsatellites 71
2.9.2 SDs and coding genes: the fate of genes in SDs 72
2.10 SDs and epigenetic modifications 75
2.11 The adaptive potential of SDs: between the benefit of innovation and the cost of pathology 78
2.11.1 The organism’s defense: immune system 79
2.11.2 Nutrient/food assimilation 80
2.11.3 Sensory perception of the environment 80
2.11.4 Neurological processes 82
2.11.5 Reproduction and the X and Y chromosomes: true SD concentrates 83
2.12 SDs and associated CNVs: their roles in species adaptation to changes in environments 86
2.12.1 SDs: a link between genomic architecture, adaptive potential and environmental changes? 86
2.12.2 Adaptation to global environmental stress 86
2.12.3 Adaptation to nutrient-poor surroundings 88
2.12.4 Adaptation to low and high temperatures 88
2.12.5 Heavy-metal adaptation 89
2.12.6 Antibiotics and drugs 90
2.12.7 Pesticide resistance 90
2.12.8 Domestication and post-domestication of plant and animal species 91
2.12.9 Competition and evolutionary success: invasive species and hybridization 93
2.13 Conclusion 94
2.14 Glossary of terms 95
2.15 References 96
Chapter 3 Transposable Elements: Parasites that Shape Genome Evolution 117
Amandine BONNET, Karine CASIER, Clément CARRÉ, Laure TEYSSET and Pascale LESAGE
3.1 Transposable elements in eukaryotic genomes 117
3.1.1 TEs: essential components of eukaryotic genomes 118
3.1.2 Acquisition of new TEs by horizontal transfer 119
3.2 Classification of TEs and transposition mechanisms 120
3.2.1 Class I retrotransposons 120
3.2.2 Class II DNA transposons 123
3.3 TE self-regulation 123
3.3.1 Spatio-temporal regulation of TE expression 124
3.3.2 Self-regulation of transposition efficiency 125
3.3.3 Selective integration to better protect the genome 125
3.4 TE restriction by the host 129
3.4.1 Transcriptional repression of genomic copies 129
3.4.2 TE transcripts: choice targets for multiple restrictions 132
3.4.3 The Swiss knives of TE restriction: piRNAs 134
3.4.4 Reverse transcription of retroelements: a key step to inhibit 139
3.5 The impact of transposition events on genomes 140
3.5.1 The structural and functional consequences of TE activity on the genome 140
3.5.2 Pathologies associated with TE activity 144
3.5.3 The impact of TEs on the evolution of the host 148
3.6 Conclusion 155
3.7 References 156
Chapter 4 Insights Into the Evolutionary Diversity of Centromeres 181
Nuria CORTES-SILVA, Aruni P SENARATNE and Ines A DRINNENBERG
4.1 The centromere 181
4.1.1 Definition and historical background 181
4.1.2 Two main types of centromeric architectures 183
4.2 Monocentromeres 184
4.2.1 The diversity of monocentric architectures across fungi 184
4.2.2 Animal and plant models contain long repetitive regional centromeres 190
4.3 Holocentromeres 192
4.3.1 Nematodes 193
4.3.2 Plants 195
4.3.3 Insects 196
4.4 Open questions 198
4.5 Acknowledgments 198
4.6 References 198
Chapter 5 Evolution and Functions of Telomeres 207
Arturo LONDOÑO-VALLEJO
5.1 Primary structure of telomeres 207
5.1.1 Origin and evolution of telomeres 210
5.1.2 Nucleoprotein structure of telomeres 212
5.2 A telomere specific higher order structure: the T-loop 215
5.2.1 Telomere replication, a fundamental mechanism for telomere maintenance 215
5.3 Telomere lengthening mechanisms 220
5.4 Telomere length homeostasis 222
5.5 Telomeres and genome organization and function 225
5.6 Cell senescence, aging and disease 226
5.7 Conclusion 227
5.8 Acknowledgments 227
5.9 References 227
Chapter 6 G-quadruplexes: Structure, Detection and Functions 239
Emilia Puig LOMBARDI
6.1 From guanine-guanine base-pairing to a secondary structure 239
6.1.1 G-quartets 239
6.1.2 Folding into a G-quadruplex structure 241
6.2 The G4 structure: variations on a theme 243
6.2.1 RNA G-quadruplexes (rG4) 245
6.2.2 Exceptions to the rule(s): non-canonical G-quadruplexes 245
6.3 Finding G-quadruplexes in a genome 246
6.3.1 Experimental methods for G-quadruplex detection 247
6.3.2 Computational methods 250
6.4 Biological roles of G-quadruplexes 257
6.4.1 First role attributed to quadruplexes: their formation in
telomeres 257
6.4.2 Predictions based on bioinformatic analyses 259
6.5 Perspective: G-quadruplexes as anticancer therapeutic targets 261
6.6 References 264
Chapter 7 Satellite DNA, Microsatellites and Minisatellites 273
Wilhelm VAYSSE-ZINKHÖFER and Guy-Franck RICHARD
7.1 Satellite DNAs, origin and definition 273
7.1.1 Minisatellites 274
7.1.2 Microsatellites 274
7.2 From semantics to biology 275
7.2.1 Distribution of satellite DNAs in genomes 275
7.2.2 Polymorphic genetic markers 277
7.2.3 Trinucleotide repeat expansions 281
7.2.4 Microsatellites regulate gene expression 283
7.2.5 Minisatellites are important in cell adhesion 285
7.2.6 Function of megasatellites 287
7.2.7 Centromeric satellite DNA, complexity of structure-function studies 288
7.3 The evolutionary mechanisms of tandem repeats 289
7.3.1 Historical model of slippage during replication 290
7.3.2 Slippage during DNA repair 292
7.3.3 Repeat expansions and contractions during homologous recombination 292
7.4 Microsatellites in human diseases 297
7.4.1 Triplet repeat expansion disorders 297
7.4.2 Colorectal cancers and the mismatch repair system 298
7.4.3 Fragile sites 299
7.5 De novo formation and evolution of tandem repeats 300
7.5.1 Birth and death of microsatellites 300
7.5.2 Formation of minisatellites 304
7.6 Perspectives 307
7.6.1 Inadequacy of software tools 307
7.6.2 The importance of definitions in biology 310
7.7 Acknowledgments 311
7.8 References 311
Chapter 8 CRISPR-Cas: An Adaptive Immune System 319
Marie TOUCHON
8.1 A brief history of the discovery of CRISPR-Cas systems 319
8.2 General characteristics of CRISPR-Cas systems 323
8.2.1 Diversity of repeats 324
8.2.2 Diversity and origin of spacers 325
8.2.3 Diversity and evolutionary classification of cas genes 327
8.2.4 Origin of CRISPR-Cas systems 329
8.3 Evolution of CRISPR-Cas systems 330
8.3.1 Scattered distribution of CRISPR-Cas systems 330
8.3.2 Massive transfer of CRISPR-Cas systems 331
8.3.3 Commonly lost systems 332
8.3.4 Evolutionary dynamics of CRISPR arrays 333
8.4 An adaptive immune system 334
8.4.1 A three-stage immune response 334
8.4.2 Diversity of CRISPR-Cas molecular mechanisms 337
8.4.3 Self- and none self-discrimination: avoiding self-targeting by CRISPR 340
8.5 Phage escape mechanisms 341
8.5.1 Genomic modifications 341
8.5.2 Anti-CRISPR proteins 343
8.6 Biological cost of CRISPR-Cas systems 344
8.6.1 Cost of expression 344
8.6.2 Cost of autoimmunity 345
8.6.3 The genetic background of the host 346
8.6.4 Limiting horizontal gene transfer 347
8.6.5 Naïve and primed adaptation 348
8.7 Importance in nature: impact of ecological factors 349
8.7.1 Phage diversity - mutation rate 349
8.7.2 Phage diversity - population size 350
8.7.3 Infectious risk - alternative strategies 350
8.8 Conclusions and perspectives 351
8.9 References 353
List of Authors 361
Index 363
