Somatic Genome Variation

in Animals, Plants, and Microorganisms

Xiu-Qing Li

• Publisher: Wiley-Blackwell
• Year: 2017
• Print ISBN:
  9781118647066
• eBook ISBN:
  9781118647127
• Edition: 1
• Topic: Sciences biologiques
• Subtopic: Génétique et génomique

Written by an international team of experts, Somatic Genome Variation presents a timely summary of the latest understanding of somatic genome development and variation in plants, animals, and microorganisms. Wide-ranging in coverage, the authors provide an updated view of somatic genomes and genetic theories while also offering interpretations of somatic genome variation. The text provides geneticists, bioinformaticians, biologist, plant scientists, crop scientists, and microbiologists with a valuable overview of this fascinating field of research.

Part I
Somatic Genome Variation in Animals and Humans

Chapter 1
Polyploidy in Animal Development and Disease

Jennifer L. Bandura¹ and Norman Zielke^2*

¹Biology Department, Roanoke College, Salem, USA

²Genome-Scale Biology Research Program, Institute of Biomedicine, University of Helsinki, Helsinki, Finland

^* Corresponding author: [email protected] Bandura J.L. and Zielke N. (2017) Polyploidy in animal development and disease. In: Li X.-Q., editor. Somatic Genome Variation in Animals, Plants, and Microorganisms: Wiley-Blackwell, Hoboken, NJ, Ch. 1, pp. 3-44.

Abstract

Somatic polyploidization is a developmentally controlled process that can be found in many animal species, including mammals. Polyploidy is utilized as a mechanism to amplify gene expression via an increase in DNA copy number, to drive cellular growth, and to initiate cellular differentiation. Moreover, polyploidy has been implicated in the response to injury or disease. This chapter discusses the processes by which polyploid cells arise and the underlying molecular mechanisms, with a focus on endoreplication in Drosophila and mice. In addition, it summarizes recent progress on the related subjects of endomitosis, ploidy reversal, and gene amplification.

Keywords polyploidy; endoreplication; endomitosis; gene amplification

1.1 Introduction

A fundamental characteristic of the canonical eukaryotic cell cycle is that the genome is only replicated once per cycle, and becomes then equally distributed between two daughter cells during the following mitosis. This strict constraint on DNA replication ensures that each daughter cell receives exactly one diploid set of chromosomes. However, some cell types depart from this rule and differentiate into viable polyploid cells, in which the entire set of chromosomes has been multiplied. While the term polyploid refers to cells with virtually any chromosomal configuration, the term polytene refers to a subclass of polyploid cells in which sister chromatids remain closely associated in parallel arrays. The degree of polyploidy is indicated by the C-value, which represents the DNA content as a multiple of the normal haploid genome. Hence, tetraploid cells have a DNA content of 4 C, while octoploid cells are 8 C. Polyploidy is clearly distinguishable from aneuploidy, which refers to cells containing an aberrant number of chromosomes that is not a multiple of the haploid genome. Polyploidy is often confused with the term re-replication, which describes genome duplications originating from unscheduled initiation of DNA replication during S phase. DNA re-replication is an aberrant event that produces cells characterized by a heterogeneous DNA content, incomplete chromosome duplications, stalled replication forks, and DNA damage. In cells with a compromised DNA damage response, re-replication events can cause genomic instability and thereby promote cancer formation.

Polyploidy occurs in two forms that can be distinguished by their mechanisms of origin: Germline polyploidy refers to genome duplications in the germline, which are often caused by chromosome mis-segregation during meiosis. In this case, all the cells in the resulting progeny will be polyploid and, because the multiplied chromosomes may be inherited by future generations, germline polyploidization is generally thought to promote speciation. In this chapter, we focus on the more common somatic polyploidy, which is often intrinsically connected to cellular differentiation and is therefore also referred to as developmentally programmed polyploidy. Somatic polyploidy occurs frequently in ferns, flowering plants, mollusks, arthropods, amphibians, and fish, but is also found in a few specialized cell types in mammals. Somatic polyploidy is utilized to increase tissue size, to initiate cell differentiation, and to multiply gene copy number to enhance tissue-specific functions. Somatic polyploidy has also been implicated in tissue regeneration and the suppression of tumorigenesis.

1.2 Mechanisms Inducing Somatic Polyploidy

The formation of somatic polyploid cells relies on four distinct mechanisms: cell fusion, acytokinetic mitosis, endomitosis, and endoreplication (Figure 1.1; Table 1.1).

Figure 1.1 Mechanisms introducing somatic polyploidy. (A) Nuclear configurations in mitotic and polyploid cell types. C, C-value, multiples of the haploid DNA content arising from different mechanisms. (B) Overview of non-canonical cell cycle variants leading to somatic polyploidy. Hepatocytes (HPC) bypass cytokinesis, and as a consequence this cell cycle variant is called an acytokinetic mitosis. Megakaryocyte polyploidization occurs through endomitosis, which is another abortive mitosis lacking anaphase B, telophase, and cytokinesis. Mouse trophoblast giant cells (TGC) and Drosophila salivary glands (SG) both undergo endocycles, which are completely devoid of M phase. TGCs undergo full genome replications, while SGs exit S phase before completing late replication. (C) Schematic of an under-replicated region, which results from differential firing of replication origins and within the euchromatin usually encompasses 100–400 kb. (D) Genomic organization of amplified loci, which arise from reiterative origin firing, resulting in copy number gradients stretching approximately 100 kb.

Table 1.1 Polyploidization achieved by varying mechanisms across animal species.

Organism	Tissue/cell type	Developmental stage	Maximal ploidy	Mechanism of polyploidization	Reference
C. elegans	Hypodermis	Larva and adult	16 C ^a	Cell fusion, Endocycles	(Flemming et al. 2000)
	Intestine	Larva	32 C	Endocycles	(Hedgecock and White 1985)
D. melanogaster	Salivary gland	Larva	1035 C	Endocycles	(Hammond and Laird 1985b)
	Ovary/follicle cell	Adult	16 C	Endocycles	(Hammond and Laird 1985a)
	Ovary/nurse cell	Adult	1500 C	Endocycles	(Hammond and Laird 1985a)
	Brain/subperineural glia	Larva	22 C	Endocycles, Acytokinetic mitosis	(Unhavaithaya and Orr-Weaver 2012)
	Fat body	Adult	256 C	Endocycles	(Richards 1980)
	Malpighian tubules	Adult	256 C	Endocycles	(Lamb 1982)
	Mechanosensory bristles	Pupa	8 C	Endocycles	(Hartenstein and Posakony 1989; Audibert et al. 2005)
	Hindgut/rectal papillae	Larva and pupa	16 C	Endocycles ^b	(Fox et al. 2010)
	Midgut	Adult	64 C	Endocycles	(Lamb 1982)
	Epidermis	Throughout development	1300 C	Endocycles	(Ganot and Thompson 2002)
O. dioica	Liver/hepatocytes	Postnatal (onset ~ 3 weeks)	8 C–16 C	Acytokinetic mitosis ^b, ^c	(Guidotti et al. 2003; Wirth et al. 2006; Margall-Ducos et al. 2007)
M. musculus	Placenta/trophoblast giant cells	Embryo (onset at E4.5)	512 C–1024 C	Endocycles ^c	(Barlow and Sherman 1974; Varmuza et al. 1988; Sher et al. 2013)
M. musculus, H. sapiens	Megakaryocytes	Embryo (onset at E7.5)	128 C	Endomitosis, Acytokinetic mitosis	(Nagata et al. 1997; Ravid et al. 2002; Sher et al. 2013)
	Heart/cardiomyocytes	Postnatal (onset at day 4)	8 C	Acytokinetic mitosis ^c	(Soonpaa et al. 1996; Pandit et al. 2013)
H. sapiens	Skin/keratinocytes	Throughout development	12 C	Endocycles, Acytokinetic mitosis	(Zanet et al. 2010; Gandarillas 2012)

Note: This is not a comprehensive list of all polyploid tissues in animals.

^a There are 65 nuclei per hypodermis.

^b Also undergo ploidy reversal.

^c Additional unidentifiedmechanisms.

1.2.1 Cell Fusion

Cell fusion describes the fusion of two cells residing in G1 phase, which results in the formation of a multinucleated cell. A striking example is found during the development of nematodes such as Caenorhabditis elegans, whose hypodermis is a single syncytium that grows through successive cell fusion events (Flemming et al. 2000). Cell fusion also occurs during the fusion of skeletal muscle myoblasts into myotubes, when monocytes differentiate into osteoclasts, and during the formation of syncytiotrophoblasts in the human placenta (Cross 2005).

1.2.2 Acytokinetic Mitosis

Acytokinetic mitosis refers to an abortive ...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• List of Contributors
• Preface and Introduction
• Acknowledgments
• About the Editor
• Part I: Somatic Genome Variation in Animals and Humans
• Part II: Somatic Genome Variation in Plants
• Part III: Somatic Genome Variation in Microorganisms
• Part IV: General Genome Biology
• Index
• End User License Agreement