Trajectories of Genetics

Bernard Dujon is Professor Emeritus at Sorbonne University, France and at the Pasteur Institute in Paris. He is a member of the French Academy of Sciences and his research focuses on eukaryotic genomes. Georges Pelletier, agronomist and member of the French Academy of Sciences, is currently honorary research director at INRA – the French National Institute for Agriculture. His research focuses on the mechanisms of genetic exchange of cytoplasmic genomes.

Introduction ix

Chapter 1. Following Ariadne’s Thread from Genetics to DNA 1

1.1. The birth of genetics 1

1.2. The foundations of a new science 5

1.3. Gene, locus and genetic maps 7

1.4. Mutagenesis: first ideas on the material nature of the gene 10

1.5. First ideas on gene products 13

1.6. The order of things and the elements of disorder 14

1.7. Dissecting the invisible: allelism, cistron and the locus again 16

1.8. The DNA trail 19

1.9. Important ideas to remember 21

1.10. References 21

Chapter 2. The Molecular Nature of Genes and Their Products 25

2.1. DNA and its replication 25

2.2. Permanence and alteration of DNA, mutations 26

2.3. Protein synthesis and the central dogma of molecular biology 28

2.4. The genetic code: how to read the genetic message 35

2.5. First paradigm of gene expression: the bacterial lactose operon 40

2.6. Reverse transcription and retrogenes 43

2.7. Exons, introns and splicing: the first complexity of RNA life 44

2.8. Sequence editing: the second complexity of RNA life 51

2.9. RNA interference and epigenetics 52

2.10. Important ideas to remember 56

2.11. References 57

Chapter 3. Chromosomes and Reproduction 61

3.1. The “true” chromosomes 61

3.2. Sexual reproduction and alternating generations 63

3.3. Meiosis 65

3.4. Genetic determinism of sex 70

3.4.1. From gametes to sex 70

3.4.2. Sex determinism in animals 71

3.4.3. Sex determinism of brown algae 74

3.5. Clonal reproduction and its derivatives 75

3.6. The genetics of organelles 77

3.6.1. In unicellular eukaryotes 78

3.6.2. In humans and animals 78

3.6.3. In plants 79

3.7. Important ideas to remember 80

3.8. References 81

Chapter 4. From Genetic Engineering to Genomics 83

4.1. Restriction of DNA 83

4.2. Recombinant DNA and the birth of genetic engineering 85

4.3. Sequencing of biological macromolecules 87

4.4. The beginnings of genomics: the very first genome sequences 91

4.5. The trigger 92

4.6. The impact of the first real genomes 93

4.7. The human genome 96

4.8. New methods of genome sequencing and the current state of genomics 98

4.9. Important ideas to remember 100

4.10. References 101

Chapter 5. Uniqueness and Polymorphism of Genomes 103

5.1. The immensity of nucleic acid sequences 104

5.2. Components of genomes and their replication 105

5.3. A little perspective on the content of genomes 109

5.4. Traces of the past and driving forces for the future 112

5.5. Genes in genomes 117

5.6. Genes and genetic determinism 120

5.7. Natural populations: pan-, core-genomes and SNP 123

5.8. Population genomics 126

5.9. The genetics of genomes 127

5.10. Important ideas to remember 128

5.11. References 129

Chapter 6. Natural Dynamics and Directed Modifications of Genomes 131

6.1. The dynamics of genomes 131

6.2. Hereditary acquisitions 134

6.2.1. Transformation by DNA and horizontal gene transfer 134

6.2.2. Primary endosymbioses of eukaryotes 136

6.2.3. Viruses and transposable elements 137

6.3. Directed manipulations of genomes: principles and tools 139

6.4. Directed manipulations of genomes: applications 144

6.5. Important ideas to remember 146

6.6. References 147

Chapter 7. Of Genes and Humans 149

7.1. Ancient DNA and human history 150

7.2. Traces of the past in today’s human genome 153

7.2.1. Adaptations to the world’s regions 154

7.2.2. Adaptations to lifestyles 154

7.2.3. Adaptations to diseases 155

7.2.4. Maladaptation following past selections 156

7.2.5. Conclusion 157

7.3. Traces of past climates in the trees of our forests 157

7.4. The domestication of cultivated plants 159

7.4.1. Characteristics of domestication 160

7.4.2. The mutations that enabled domestication 162

7.5. Selection of livestock 163

7.6. Conclusion 167

7.7. Important ideas to remember 168

7.8. References 169

Chapter 8. Genetics and Human Health 173

8.1. “Mendelian” and multifactorial diseases, a continuum of complexity 174

8.2. Interpretation and use of DNA sequences 175

8.3. Autism 177

8.4. Gene therapy 178

8.5. The multiple genetic causes of cancers 181

8.6. Microbiota 184

8.7. Important ideas to remember 187

8.8. References 188

Chapter 9. Now and Tomorrow 191

9.1. A living world to be further explored 191

9.2. Genome synthesis 197

9.3. New lives 200

9.4. Important ideas to remember 203

9.5. References 203

Conclusion 207

Glossary 213

References 233

Index 235