The Expanding Repertoire of RNA ........................................................................................................

87
Spliceosomal RNAs ................................................................................................................................87 Small
Nucleolar RNAs ............................................................................................................................88 Other Small
Guide, Scaffolding and Regulatory RNAs .........................................................................90 Catalytic RNAs and
the Ancient RNA World Hypothesis .....................................................................93 The Catalytic Heart of
Splicing and Translation ....................................................................................94 The Digital and Analog Faces
of RNA ...................................................................................................95 Candles in the
Dark .................................................................................................................................95 Further
Reading ......................................................................................................................................96 Chapter 9
Glimpses of a Modern RNA World .........................................................................................................97
Riboregulators .........................................................................................................................................97
Riboswitches ...........................................................................................................................................99
Antisense RNAs and Complex Transcription in Eukaryotes ................................................................100 Long
Untranslated RNAs ...................................................................................................................... 101 UTR-
Derived RNAs ..............................................................................................................................107 First
Examples of Small Regulatory RNAs in Animals .......................................................................107 Curiosities or
Emissaries? .....................................................................................................................107 Further
Reading ....................................................................................................................................109 Chapter 10
Genome Sequences and Transposable Elements ................................................................................... 111
Genome Mapping .................................................................................................................................. 111
Genetics at Genome Scale ..................................................................................................................... 111
Whole Genome Sequencing of Bacteria and Archaea .......................................................................... 112
Genome Sequencing of Unicellular Eukaryotes ................................................................................... 112
Genome Sequencing of Model Plants and Animals.............................................................................. 114 The
G-Value Enigma ............................................................................................................................. 114
Comparative Genomics at Nucleotide Resolution ................................................................................. 116
Pseudogenes and Retrogenes ................................................................................................................. 118
Transposable Elements .......................................................................................................................... 118
Transposable Elements as Functional Modules .................................................................................... 119
Transposable Elements as Drivers of Phenotypic Innovation ...............................................................120 The
Great Exploration – The Diversity of Life .....................................................................................122 From
Genome Sequence to Genome Biology .......................................................................................123 Further
Reading ....................................................................................................................................124 Chapter 11
The Human Genome .............................................................................................................................125 The
Project ............................................................................................................................................125
Assessment of Functionality .................................................................................................................126 The
Majority of the Genome Is Active..................................................................................................128 Damaged
Genes ....................................................................................................................................129 A Plethora of
‘Rare Diseases’ ...............................................................................................................130 Complex Traits and
Disorders ...............................................................................................................132 The Transformation of
Medical Research and Healthcare ...................................................................134 Further
Reading ....................................................................................................................................135 viii Contents
Chapter 12 Small RNAs with Mighty
Functions .....................................................................................................137 Unusual Genetic Phenomena
Involving RNA .......................................................................................137 The RNA Interference
Pathway ............................................................................................................138 Transcriptional Gene
Silencing: RNA-Directed DNA Methylation .....................................................140 Research and Biotechnology
Applications ............................................................................................ 141
MicroRNAs ........................................................................................................................................... 142 Piwi-
Associated RNAs ..........................................................................................................................144 Other
Classes of Small RNAs ............................................................................................................... 145 RNA
Communication between Species ................................................................................................146
CRISPR ................................................................................................................................................. 147 RNA-
Directed Genome Editing ............................................................................................................ 148 Further
Reading ....................................................................................................................................150 Chapter 13
Large RNAs with Many Functions ....................................................................................................... 153
Pervasive Transcription ......................................................................................................................... 153 The
Amazing Complexity of the Transcriptome ..................................................................................154 Protein-
Coding or Noise? ......................................................................................................................156 The
Restricted Expression of Long Non-coding RNAs ........................................................................157 Other
Indices of Functionality ..............................................................................................................158 Genetic
Signatures ................................................................................................................................160 An Avalanche
of Long Non-coding RNAs ........................................................................................... 163 A Plethora of
Functions ......................................................................................................................... 165 The Wild
West ....................................................................................................................................... 167 Further
Reading .................................................................................................................................... 168 Chapter 14
The Epigenome ...................................................................................................................................... 171
Chromatin Structure .............................................................................................................................. 171
Topological Domains ............................................................................................................................ 171
Enhancers .............................................................................................................................................. 173
Nucleosomes and Histones .................................................................................................................... 176
Nucleosome Remodeling ....................................................................................................................... 178
Histone Modifications ........................................................................................................................... 178 The
Histone Code ..................................................................................................................................180 DNA
Methylation .................................................................................................................................. 183 The
Regulation of Development ............................................................................................................ 186 Further
Reading .................................................................................................................................... 186 Chapter 15
The Programming of Development ....................................................................................................... 187
Autopoiesis ............................................................................................................................................ 187 The
Overarching Question .................................................................................................................... 187 Tissue
Architecture and Cell Identity ................................................................................................... 188
Programmed Ontogeny ......................................................................................................................... 189
Lineage Specification ............................................................................................................................192 How
Much Information Is Required? ...................................................................................................193
Constraints Imposed by the Superlinear Scaling of Regulatory Information ......................................195 How
Much Information Is There in the Human Genome? ...................................................................196 Genomes
as .zip Files of Transcriptomes ..............................................................................................196 Further
Reading ....................................................................................................................................197 ix C ontents
Chapter 16 RNA
Rules ............................................................................................................................................199 RNA Is a
Core Component of Chromatin .............................................................................................199 Regulation of
Chromosome Structure ...................................................................................................199 RNA Guidance of
Chromatin Remodeling ...........................................................................................199 Guidance of
Transcription Factors ........................................................................................................201 Guidance of DNA
Methylation .............................................................................................................203 Guidance of Histone
Modifications ......................................................................................................204 Xist as the
Exemplar ..............................................................................................................................205 Enhancer RNAs
and Chromatin Structure ...........................................................................................206 RNA Scaffolding of
Phase-Separated Domains ...................................................................................208 An Addition to the
Ancient RNA World Hypothesis ............................................................................ 211 Structure-Function
Relationships in lncRNAs ...................................................................................... 212 A New View of the
Genome of Complex Organisms ........................................................................... 213 Further
Reading .................................................................................................................................... 214 Chapter 17
Plasticity ................................................................................................................................................ 215 RNA
Modifications and the Unknown Epitranscriptome ..................................................................... 215 The
Expansion of RNA Editing in Cognitive Evolution ....................................................................... 217 A>I Editing
...................................................................................................................................... 217 C>U
Editing .....................................................................................................................................222 The
Brain ...............................................................................................................................................223 RNA-
Directed Transgenerational Epigenetic Inheritance ....................................................................225 Further
Reading ....................................................................................................................................228 Chapter 18
Beyond the Jungle of Dogmas ...............................................................................................................229 The
Misunderstanding of Molecular Biology .......................................................................................229 The
Evolution of Evolvability ................................................................................................................230 Further
Reading .................................................................................................................................... 231
References ...........................................................................................................................................................
.......233