Somatic Genome Variation: in Animals, Plants, and Microorganisms

A comprehensive review and integration of cutting–edge research worldwide that is revolutionizing science s understanding of genetic variation and inheritance 

Somatic Genome Variation in Animals, Plants and Microorganisms provides a wide–ranging review of one of the most exciting and promising areas of genomics research. Featuring contributions from a team of distinguished researchers from around the world, it summarizes the growing body of evidence for developmental and environmental genome variation in microorganisms, plants, and animals while offering authoritative interpretations of identified genome variations.

Research currently underway at laboratories worldwide has begun to overturn many fixed beliefs about the nature of somatic genomes. For example, it has long been held that, except for epigenetic variation and occasional mutations caused by external mutagens, somatic cells are genetically identical and contribute nothing to inheritance; that gene transcript abundance is determined purely by promoter activity and RNA stability; and that clones have the same genome. The evidence assembled in this book challenges those assumptions, shedding new light on changes that occur to primary nucleotide sequences and ploidy of nuclear and cytoplasmic genomes during somatic development. The authors explore somatic genome variation, update various basic concepts in genetics and breeding, consider the implications of somatic genome variation for human health and agriculture, and propose an updated synthesis of inheritance supported by the evidence. 

Provides an updated view of somatic genomes and fundamental genetic theories while also offering interpretations of somatic genome variation Features wide–ranging coverage of developments at the forefront of one of today s most fascinating fields of research Increases our understanding of genetic variation that occurs during development and in response to environment  Authored by a global team of experts in the field it presents up–to–date coverage of somatic genomes and genetic theories 

Somatic Genome Variation in Animals, Plants and Microorganisms is an important source of information and inspiration for geneticists, bioinformaticians, biologists, plant scientists, crop scientists, and microbiologists, as well as biomedical researchers.

List of Contributors

Preface and Introduction

Acknowledgments

About the Author

Part 1 Somatic Genome Variation in Animals and Humans

1 Polyploidy in Animal Development and Disease
Jennifer L. Bandura and Norman Zielke

1.1 Introduction

1.2 Mechanisms Inducing Somatic Polyploidy

1.2.1 Cell Fusion

1.2.2 Acytokinetic Mitosis

1.2.3 Endomitosis

1.2.4 Endoreplication

1.2.5 Gene Amplification

1.2.6 Ploidy Reversal

1.3 The Core Cell Cycle Machinery

1.4 Genomic Organization of Polyploid Cells

1.5 Endoreplication: An Effective Tool for Post–Mitotic Growth and Tissue Regeneration

1.6 Initiation of Endoreplication in Drosophila

1.6.1 Endocycle Entry in Ovarian Follicle Cells

1.6.2 Signaling Pathways Regulating the Mitotic–to–Endocycle Switch

1.6.3 Endocycle Entry in Other Tissues

1.7 Mechanisms of Endocycle Oscillations in Drosophila

1.7.1 An Automous Oscillator Drives Endocycling in the Salivary Glands

1.7.2 Alternative Modes of Endoreplication

1.8 Gene Amplification in Drosophila Follicle Cells

1.8.1 Molecular Mechanism of Gene Amplification

1.8.2 The Endocycle–to–Amplification Switch

1.9 Endocycle Entry in the Trophoblast Lineage

1.10 Mechanisms of Endocycle Oscillations in Trophoblast Giant Cells

1.11 Cardiomyocytes

1.11.1 Upstream Control of Cardiomyocyte Polyploidization

1.11.2 Mechanisms of Cardiomyocyte Polyploidization

1.11.3 Polyploidization as a Response to Tissue Damage

1.12 Hepatocytes

1.12.1 Mechanisms of Hepatocyte Polyploidization

1.12.2 The Ploidy Conveyor Model

1.12.3 Liver Regeneration

1.13 Megakaryocytes

1.13.1 Mechanisms of MKC Polyploidization

1.14 Concluding Remarks

2 Large–Scale Programmed Genome Rearrangements in Vertebrates
Jeramiah J. Smith

2.1 Introduction

2.2 Hagfish

2.2.1 Content of Eliminated DNA

2.2.2 Results and Mechanisms of Deletion

2.3 Sea Lamprey

2.3.1 Content of Eliminated DNA

2.3.2 Results and Mechanisms of Deletion

2.4 Zebra Finch

2.4.1 Mechanisms of Deletion

2.4.2 Content of Eliminated DNA

2.5 Emerging Themes and Directions

2.5.1 The Biological Function of PGR

2.5.2 Mechanisms of Deletion

2.5.3 Other Vertebrates?

3 Chromosome Instability in Stem Cells
Paola Rebuzzini, Maurizio Zuccotti, Carlo Alberto Redi, and Silvia Garagna

3.1 Introduction

3.2 Pluripotent Stem Cells and iPSCs

3.2.1 Primate Embryonic Stem Cells

3.2.2 Mouse Embryonic Stem Cells

3.2.3 Parthenogenetic Embryonic Stem Cells

3.2.4 Induced Pluripotent Stem Cells

3.3 Somatic Stem Cells

3.3.1 Mesenchymal Stem Cells

3.3.2 Neural Stem Cells

3.4 Mechanisms of Chromosomal Instability

3.4.1 Dysfunction in the Spindle Assembly Checkpoints

3.4.2 Defects of Microtubule Attachment to the Kinetochore

3.4.3 Supernumerary Centrosomes

3.4.4 Sister Chromatids Cohesion

3.5 Mechanisms of Chromosomal Instability in Stem Cells

Part 2 Somatic Genome Variation in Plants

4 Mechanisms of Induced Inheritable Genome Variation in Flax
Christopher A. Cullis

4.1 Introduction

4.2 Restructuring the Flax Genome

4.3 Specific Genomic Changes

4.4 What Happens when Plastic Plants Respond to Environmental Stresses?

4.5 When Do the Genomic Changes Occur and Are they Adaptive?

4.6 Is this Genomic Response of Flax Unique?

4.7 Concluding Remarks

5 Environmentally Induced Genome Instability and its Inheritance
Andrey Golubov

5.1 Introduction

5.2 Stress and its Effects on Genomes

5.2.1 Genetic Changes

5.2.2 DNA Repair

5.2.3 Epigenetic Changes

5.2.3.1 DNA Methylation

5.2.3.2 Histone Modifications

5.2.4 The Link between Genetic and Epigenetic Changes

5.3 Transgenerational Inheritance

5.4 Concluding Remarks and Future Directions

6 The Mitochondrial Genome, Genomic Shifting, and Genomic Conflict
Gregory G. Brown

6.1 Introduction

6.2 Heteroplasmy and Sublimons

6.3 Cytoplasmic Male Sterility (CMS) in Plants

6.4 Mitochondrial Sublimons and CMS

6.5 Restorer Gene Evolution: Somatic Genetic Changes Drive Nuclear Gene Diversity?

6.6 Concluding Remarks

7 Plastid Genome Stability and Repair
Éric Zampini, Sébastien Truche, Étienne Lepage, Samuel Tremblay–Belzile, and Normand Brisson

7.1 Introduction

7.2 Characteristics of the Plastid Genome

7.2.1 General Composition of the Plastid Genome

7.2.2 The Structure of the Plastid Genome

7.3 Replication of Plastid DNA

7.3.1 Plastid DNA Content during Development

7.3.2 Plastid DNA Replication Machinery

7.3.3 Replication Mechanisms

7.3.4 Origins of Replication

7.3.5 Nucleus and Plastid Coordination during DNA Replication

7.4 Transcription in the Plastid

7.5 The Influence of Replication and Transcription on Plastid Genome Stability

7.6 Plastid Genome Stability and DNA Repair

7.6.1 Oxydative Stress, Photo–Adaptation, and ROS Detoxification

7.6.2 UV–Induced DNA Damage

7.6.3 Recomination and DNA Double–Strand Break Repair

7.7 Outcomes of DNA Rearrangements

7.8 Concluding Remarks

Part 3 Somatic Genome Variation in Microorganisms

8 RNA–Mediated Somatic Genome Rearrangement in Ciliates
John R. Bracht

8.1 Introduction

8.2 Ciliates: Ubiquitous Eukaryotic Microorganisms with a Long Scientific History

8.3 Two s Company: Nuclear Dimorphism in Ciliates

8.4 Paramecium: Non–Mendelian Inheritance Comes to Light

8.5 Tetrahymena and the Origin of the ScanRNA Model

8.6 Small RNAs in Stylonychia and Oxytricha

8.7 Long Non–Coding RNA Templates in Genome Rearrangement

8.8 Long Non–Coding RNA: An Interface for Short Non–Coding RNA

8.9 Short RNA–Mediated Heterochromatin Formation and DNA Elimination

8.10 Transposable Elements and the Origins of Genome Rearrangements

8.11 Transposons, Phase Variation, and Programmed Genome Engineering in Bacteria

8.12 Transposases, Non–Coding RNA, and Chromatin Modifications in VDJ Recombination of Vertebrates

8.13 Concluding Remarks: Ubiquitous Genome Variation, Transposons, and Noncoding RNA

9 Mitotic Genome Variations in Yeast and Other Fungi
Adrianna Skoneczna and Marek Skoneczny

9.1 Introduction

9.2 The Replication Process as a Possible Source of Genome Instability

9.2.1 DNA Polymerases as Guardians of Genome Maintenance

9.2.2 dNTP Cellular Level and their Pool Bias Contribute to Genome Stability

9.2.3 Mismatch Repair (MMR) and Ribonucleotide Excision Repair (RER) Are Used to Clean–up after Replication

9.3 Post–Replicative Repair (PRR) or Homologous Recombnation (HR) Are Responsible for Error–Free and Error–Prone Repair of Blocking Lesions and Replication Stall–Borne Problems

9.3.1 Sumoylated PCNA–, Srs2–, and Replicative Polymerase–dependent DNA Synthesis on Damaged Template

9.3.2 Ubiqiutinated PCNA– and Specialized Pol–Dependent Translesion Synthesis

9.3.3 The Polyubiquitinated PCNA– and Rad5–Dependent Damage Avoidance Pathway

9.3.4 The Alternative PCNA–, RPA–, and 5 –Junction–Dependent Pathway Involved in Gap Filling and Telomere Maintenance

9.3.5 Crosstalk between RFC Complexes Adapts Cellular Response to Different Stresses Arising from Genome Perturbations

9.3.6 Break–Induced Replication (BIR) Is a Vastly Inaccurate Repair Pathway

9.4 Ploidy Maintenance and Chromosome Integrity Mechanisms

9.4.1 Processes that Affect Aneuploidy in Yeasts

9.4.2 Ploidy Changes in Yeasts

9.4.3 Possible Mechanism of Ploidy Change in Yeast

9.5 Concluding Remarks

Part 4 General Genome Biology

10 Genome Variation in Archaeans, Bacteria, and Asexually Reproducing Eukaryotes
Xiu–Qing Li

10.1 Introduction

10.2 Chromosome Number in Prokaryote Species

10.3 Genome Size Variation in Archaeans and Bacteria

10.4 Archaeal and Bacterial Genome Size Distribution

10.5 Genomic GC Content in Archaeans, Bacteria, Fungi, Protists, Plants, and Animals

10.6 Correlation between GC Content and Genome or Chromosome Size

10.7 Genome Size and GC–Content Variation in Primarily Asexually Reproducing Fungi

10.8 Evolution of Gene Direction

10.9 Concluding Remarks

11 RNA Polyadenylation Site Regions: Highly Similar in Base Composition Pattern but Diverse in Sequence A Combination Ensuring Similar Function but Avoiding Repetitive–Regions–Related Genomic Instability
Xiu–Qing Li and Donglei Du

11.1 General Introduction to Gene Number, Direction, and RNA Polyadenylation

11.2 Base Selection at the Poly(A) Tail Starting Position

11.3 Most Frequent Upstream Motifs in Microorganisms, Plants, and Animals

11.4 Motif Frequencies in the Whole Genome

11.5 The Top 20 Hexamer Motifs in the Poly(A) Site Region in Humans

11.6 Polyadenylation Signal Motif Distribution

11.7 Alternative Polyadenylation

11.8 Base Composition of 3 UTR in Plants and Animals

11.9 Base Composition Comparison between 3 UTR and Whole Genome

11.10 Base Composition of 3 COR in Plants and Animals

11.11 Base Composition Pattern of the Poly(A) Site Region in Protists

11.12 Base Composition Pattern of the Poly(A) Site Region in Plants

11.13 Base Composition Pattern of the Poly(A) Site Region in Animals

11.14 Comparison of Poly(A) Site Region Base Composition Patterns in Plants and Animals

11.15 Common U–A–U–A–U Base Abundance Pattern in the Poly(A) Site Region in Fungi, Plants, and Animals

11.16 Difference between the Most Frequent Motifs and Seqlogo–Showed Most Frequent Bases

11.17 RNA Structure of the Poly(A) Site Region

11.18 Low Conservation in the Overall Nucleotide Sequence of the Poly(A) Site Region

11.19 Poly(A) Site Region Stability and Somatic Genome Variation

11.20 Concluding Remarks

12 Insulin Signaling Pathways in Humans and Plants
Xiu–Qing Li and Tim Xing

12.1 Introduction

12.2 Ranking of the Insulin Signaling Pathway and its Key Proteins

12.3 Diseases Caused by Somatic Mutations of the PI3K, PTEN, and AKT Proteins in the Insulin Signaling Pathway

12.4 Plant Insulin and Medical Use

12.5 Role of the Insulin Signaling Pathway in Regulating Plant Growth

12.6 Concluding Remarks

13 Developmental Variation in the Nuclear Genome Primary Sequence
Xiu–Qing Li

13.1 Introduction

13.2 Genetic Mutation, DNA Damage and Protection, and Gene Conversion in Somatic Cells

13.3 Programmed Large–Scale Variation in Primary DNA Sequences in Somatic Nuclear Genome

13.4 Generation of Antibody Genes in Animals through Somatic Genome Variation

13.5 Developmental Variation in Primary DNA Sequences in the Somatic Cells of Plants

13.6 Heritability and Stability of Developmentally Induced Variation in the Somatic Nuclear Genome in Plants

13.7 Concluding Remarks

14 Ploidy Variation of the Nuclear, Chloroplast, and Mitochondrial Genomes in Somatic Cells
Xiu–Qing Li, Benoit Bizimungu, Guodong Zhang, and Huaijun Si

14.1 Introduction

14.2 Nuclear Genome in Somatic Cells

14.2.1 Ploidy Variation of the Individual or Species in Plants and Animals

14.2.2 Effects of Species Ploidy Variation on the Growth of Animals and Plants

14.2.3 Ploidy of Bacteria

14.2.4 Endopolyploidy in Animal and Plant Somatic Cells

14.2.5 Somatic Cell Haploidization

14.2.6 Aneuploid Cells in Plant Somatic Tissues

14.2.7 Aneuploid Cells in Cancerous Masses

14.2.8 Nuclear B Chromosomes in Somatic Cells

14.3 Ploidy Variation of the Individual or Species in Plants and Animals

14.3.1 Types of Plastids

14.3.2 Plastid Genome and its Size in Somatic Cells

14.3.3 Recombination among Repeated Sequences in the Plastid Genome

14.3.4 Integrity of the Organelle Genome in Green Leaves under Light

14.3.5 Plastid Genome Ploidy or Copy Number Variation in Somatic Cells

14.4 Effects of Species Ploidy Variation on the Growth of Animals and Plants

14.4.1 Mitochondrial Genome and its Size

14.4.2 Recombination among Repeated Sequences and Subgenomic Molecules in Mitochondria

14.4.3 Mitochondrial Subgenome Copy Number Variation in Somatic Cells

14.4.4 Nuclear and Tissue–Specific Regulation of Mitochondrial Gene Expression

14.4.5 Stoichiometric Variation and Effects on Mitochondrial Subgenomic Molecules

14.5 Organelle Genomes in Somatic Hybrids

14.6 Effects of Nuclear Genome Ploidy on Organelle Genomes

14.7 Concluding Remarks

15 Molecular Mechanisms of Somatic Genome Variation
Xiu–Qing Li

15.1 Introduction

15.2 Mutation of Genes Involved in the Cell Cycle, Cell Division, or Centromere Function

15.3 DNA Damage

15.4 Variation in Induction and Activity of Radical–Scavenging Enzymes

15.5 DNA Cytosine Deaminases

15.6 Variation in Protective Roles of Pigments against Oxidative Damage

15.7 RNA–Templated DNA Repair

15.8 Errors in DNA Repair

15.9 RNA–Mediated Somatic Genome Rearrangement

15.10 Repetitive DNA Instability

15.11 Extracellular DNA

15.12 DNA Transposition

15.13 Somatic Crossover

15.14 Molecular Heterosis

15.15 Genome Damage Induced by Endoplasmic Reticulum Stress

15.16 Telomere Degeneration

15.17 Concluding Remarks

16 Hypotheses for Interpreting Somatic Genome Variation
Xiu–Qing Li

16.1 Introduction

16.2 Cell–Specific Accumulation of Somagenetic Variation in Somatic Cells

16.3 Developmental Age and Genomic Network of Reproductive Cells

16.4 Genome Generation Cycle of Species

16.5 Somatic Genome Variation and Tissue–Specific Requirements during Growth or Development

16.6 Costs and Benefits of Somatic Genome Variation

16.7 Hypothesis on the Existence of a Primitive Stage in both Animals and Plants

16.8 Sources of Genetic Variation from in Vitro Culture Propagation

16.9 Hypothesis that Heterosis Is Created by Somatic Genome Variation

16.10 Genome Stability through Structural Similarity and Sequence Dissimilarity

16.11 Hypothesis Interpreting the Maternal Transmission of Organelles

16.12 Ability of Humans to Deal with Somatic Genome Variation and Diseases

16.13 Concluding Remarks

17 Impacts of Somatic Genome Variation on Genetic Theories and Breeding Concepts and the Distinction between Mendelian Genetic Variation, Somagenetic Variation, and Epigenetic Variation
Xiu–Qing Li

17.1 Introduction

17.2 The Term Somatic Genome

17.3 Mendelian Genetic Variation, Epigenetic Variation, and Somagenetic Variation

17.4 What Is a Gene?

17.5 Breeding Criteria, Genome Cycle, Pure Lines, and Variety Stability

17.6 The Weismann Barrier Hypothesis and the Need for Revision

17.7 Implications for Species Evolution

17.8 Concluding Remarks

18 Somatic Genome Variation: What it Is and What it Means for Agriculture and Human Health
Xiu–Qing Li

18.1 Introduction

18.2 Natural Attributes of Somatic Genome Variation

18.3 Implications of Somatic Genome Variation for Human and Animal Health

18.3.1 Cellular–Level Variation

18.3.2 Ploidy and Chromosome Number Variation of the Whole Organism

18.3.3 Endoploidy Variation

18.3.4 DNA Cytosine Deaminases, Somatic Mutation, Immunoglobulin Diversity, and Tumors

18.3.5 Mitochondrial Genome Sequence or DNA Amount Variation

18.3.6 Nuclear or Ooplasmic Transfer–based Therapy

18.3.7 Differential Treatments of Beneficial and Harmful SGVs

18.4 Implications of Somatic Genome Variation for Agriculture

18.4.1 Cellular–Level Variation

18.4.2 Ploidy and Chromosome Number Variation of the Whole Organism

18.4.3 Endoploidy Variation

18.4.4 Intra– and Interchromosomal Variation

18.4.5 Dedifferentiation– and Redifferentiation–Induced Variation

18.4.6 DNA Damage, Epigenetics, Gene Mutation, and Bud Mutation

18.4.7 Plastid Genome Sequence or DNA Amount Variation

18.4.8 Mitochondrial Genome Sequence or DNA Amount Variation

18.4.9 DNA Transfer, Organelle Transmission, and Organelle Genome Segregation

18.4.10 Intercompartmental Interaction and DNA Exchange

18.5 Concluding Remarks

Xiu–Qing Li, Doctorat d État en Sciences (France), is a senior level Research Scientist of Molecular Genetics at Agriculture and Agri–Food Canada (Government of Canada). Dr. Li is also an Adjunct Professor at the University of New Brunswick and serves as an editor on PloS ONE, Genetics and Epigeneitcs, and the Potato Journal. He is the organizer and chair for the Somatic Genome Workshop and the co–organizer for the Genome Features and Chromosome Functionality Workshop at the Plant and Animal Genome Conference, and serves as the Communication Director of the Canadian Association for Plant Biotechnology. Dr. Li is also author of Somatic Genome Manipulation: Advances, Methods, and Applications.