CHROMOSOMES: ORGANIZATION AND FUNCTION

Chromosomes
Organization and Function

Adrian T. Sumner
North Berwick, United Kingdom
© 2003 by Blackwell Science Ltd
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First published 2003

Library of Congress Cataloging-in-Publication Data

Sumner, A.T. (Adrian Thomas), 1940–
Chromosomes: organization and function/Adrian T. Sumner.
p. cm.
Includes bibliographical references and index.
ISBN 0-632-05407-7 (pbk.: alk. paper)
1. Chromosomes. I. Title.
QH600.S863 2003
572.8¢7 – dc21
2002066646

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Contents
Preface, ix
Chapter 1: Why study chromosomes? 1
1.1 Early studies of chromosomes, 1
1.2 The origin of genetics, and the
chromosome theory of inheritance, 1
1.3 The chemical nature of genes and
chromosomes, 2
1.4 The position of chromosomes in an age
of molecular biology, 3
Website, 4
Chapter 2: Mitosis, meiosis and the cell
cycle, 5
2.1 The necessity for accuracy in the cell
cycle, 5
2.2 The mitotic cycle, 6
2.3 Essentials of mitosis, 11
2.4 Other cell-cycle events must be
co-ordinated with mitosis, 15
2.5 Meiosis, 15
2.6 Accuracy is ensured in cell division, 23
Chapter 3: DNA, the genetic code, 24
3.1 Stability and variability of DNA, 24
3.2 The amount of DNA in nuclei, and the
C-value paradox, 24
3.3 Repetitive DNA – sequences with a
function, or just junk? 25
3.4 DNA replication, 31
3.5 5-Methylcytosine – epigenetic
modification of DNA, 32
3.6 DNA damage and repair, 35
3.7 DNA is dynamic, 43
Websites, 43
Chapter 4: Assembly of chromatin, 44
4.1 Introduction, 44
4.2 The nucleosome fibre, 44
4.3 Packing nucleosomes into solenoids, 54
4.4 Yet more packing, 55
4.5 Other ways to pack DNA, 55
4.6 Summary, 56
Websites, 56
Chapter 5: The chromosomes in
interphase, 57
5.1 Interphase nuclei: sites of chromosome
activity, 57
5.2 How are the chromosomes arranged in
the nucleus? 58
5.3 Where do replication and transcription
take place? 62
5.4 The nuclear matrix, 64
5.5 Other nuclear structures, 66
5.6 Interphase nuclei are highly organized
and dynamic, 68
Website, 69
Chapter 6: Structure of mitotic and
meiotic chromosomes, 70
6.1 Chromosomes of dividing and interphase
cells compared, 70
6.2 Making a mitotic chromosome, 71
6.3 Loops and scaffolds, 72
6.4 Chromosome condensation – the final
stages, 75
6.5 Biochemistry of condensation, 78
6.6 The periphery of the chromosome, 79
6.7 Meiotic and mitotic chromosomes
compared, 82
vi Contents
6.8 There is still much to be learnt about
chromosome structure, 83
Chapter 7: Constitutive
heterochromatin, 84
7.1 What is heterochromatin? 84
7.2 Where is constitutive heterochromatin on
the chromosomes? 85
7.3 What is constitutive heterochromatin
made of ? 85
7.4 What does heterochromatin do? 91
7.5 Applications of heterochromatin
staining, 95
7.6 Heterochromatin today, 96
Websites, 96
Chapter 8: Sex chromosomes and sex
determination, 97
8.1 What are sex chromosomes? 97
8.2 The evolution of sex chromosomes, 97
8.3 Sex chromosome systems and mechanisms
of sex determination, 99
8.4 Dosage compensation: coping with
different numbers of X chromosomes in
the two sexes, 102
8.5 Sex chromosomes at meiosis and
gametogenesis, 106
8.6 Sex chromosomes: different means, the
same ends, 108
Websites, 108
Chapter 9: Imprinting, 109
9.1 What is imprinting? 109
9.2 Which organisms show imprinting? 109
9.3 How does imprinting work? 112
9.4 What is imprinting for? 115
Websites, 116
Chapter 10: Euchromatin and the
longitudinal differentiation
of chromosomes, 117
10.1 What is euchromatin? 117
10.2 Euchromatin and chromosome banding
in mammals, 117
10.3 Longitudinal differentiation of
chromosomes in non-mammals, 130
10.4 The how and why of longitudinal
differentiation, 132
Chapter 11: The nucleolus and the
nucleolus organizer regions
(NORs), 133
11.1 The importance of nucleoli and
NORs, 133
11.2 The ribosomal genes, 133
11.3 Silver staining of NORs and nucleoli –
what does it mean? 136
11.4 The nucleolus in interphase, 137
11.5 What happens to the nucleolus during
cell division? 138
11.6 What else does the nucleolus do? 141
Chapter 12: Centromeres, kinetochores
and the segregation of
chromosomes, 143
12.1 What are centromeres and
kinetochores? 143
12.2 How are centromeres constructed? 143
12.3 How are kinetochores made? 149
12.4 Proteins of the centromere and
kinetochore, 149
12.5 Holocentric chromosomes, 155
12.6 Kinetochores are essential for the
functioning of chromosomes, 156
Chapter 13: Telomeres, 159
13.1 What is a telomere? 159
13.2 Telomeric DNA, 159
13.3 How do telomeres maintain
chromosome length? 161
13.4 How do telomeres protect chromosome
ends? 165
13.5 Telomeres and the spatial organization of
nuclei, 166
13.6 Telomeres, ageing and cancer, 167
Websites, 170
Chapter 14: Lampbrush
chromosomes, 171
14.1 What are lampbrush chromosomes? 171
14.2 Lampbrush chromosome
structure, 172
14.3 What have we learnt from oocyte
lampbrush chromosomes? 178
14.4 Lampbrush Y chromosomes in Drosophila
spermatocytes, 179
Websites, 180

Chapter 15: Polytene chromosomes, 182
15.1 What are polytene chromosomes? 182
15.2 Polytene chromosomes in Diptera, 183
15.3 Polytene chromosomes and macronucleus
formation in ciliates, 188
15.4 Mammalian polytene chromosomes, 190
15.5 Polytene chromosomes in plants, 191
15.6 Mechanisms of polytenization, 192
15.7 What is the point of polytene
chromosomes? 193
Websites, 193
Chapter 16: Chromosomes, the karyotype
and evolution, 194
16.1 Chromosomes and evolution, 194
16.2 Constraints on chromosome size, shape
and number, 194
16.3 Types of chromosome change during
evolution, 195
16.4 Chromosome changes and
speciation, 203
16.5 Nucleotypic effects, 204
16.6 Chromosomal change is a concomitant
of evolution, 205
Chapter 17: Chromosomes and
disease, 206
17.1 The significance of chromosomal
disease, 206
Contents vii
17.2 Numerical chromosome defects – errors
in cell division, 206
17.3 Diseases produced by chromosome
deletions and duplications, 212
17.4 Chromosome breakage syndromes –
failures in DNA repair, 213
17.5 Fragile sites and triplet repeat
diseases, 216
17.6 Diseases of imprinting, 220
17.7 DNA methylation and disease, 220
17.8 Telomeres and disease, 222
17.9 Cancer – anything and everything can
go wrong with chromosomes, 223
Websites, 227
Chapter 18: Chromosome
engineering and artificial
chromosomes, 228
18.1 Engineering chromosomes – an ancient
technique, 228
18.2 What is an artificial chromosome? 230
18.3 How to make artificial
chromosomes, 232
18.4 Artificial chromosomes – the
future, 237
References, 239
Index, 275
Preface
Several years ago, with the tidal wave of mole-
cular biology threatening to engulf and obliter-
ate the rest of biology, it might have seemed that
the study of chromosomes was something to be
left to a few old-fashioned scientists to occupy
them harmlessly until they retired. In fact,
nothing could be further from the truth, and
recently there has been an upsurge in chromo-
some studies, stimulated by these advances in
molecular biology but accompanied by the real-
ization that the arrangement of biological mole-
cules could not, on its own, explain all biological
phenomena. In fact, it has long been known that
the behaviour of chromosomes at mitosis and
meiosis determines the nature of inheritance, and
it is becoming clear that the disposition of chro-
mosomes in interphase nuclei is also important
for their functioning. Many chromosomal sub-
structures such as heterochromatin, nucleoli, cen-
tromeres and telomeres are being studied
intensively, as well as chromosomal phenomena
such as imprinting. With the immense reduction
in mortality from infectious disease in Western
societies, genetic diseases have become much
more significant, and many of these, including
spontaneous abortions and cancer, are the result
of chromosomal defects. These and other chro-
mosomal topics are covered in this book, which
is aimed at advanced undergraduate and post-
graduate students who, it is assumed, will have a
basic knowledge of chromosomes such as can be
gleaned from many excellent genetics and cell
biology textbooks.
Each chapter can be read in isolation, but in
reality no single topic is isolated from any other,
and I have cross-referenced the text quite heavily
to guide the reader to further, related informa-
tion. I have also included a substantial amount of
tabular material, which I believe is the most
satisfactory way of dealing with the vast amount
of data now available on some topics.We are sup-
posed to be living in an electronic age, and
where appropriate I have referred to websites, but
only when they supplement or complement the
material in this book. Access to additional chro-
mosomal websites can be obtained through
www.chromosome.net/index.htm
This book could never have been written
without the help of numerous scientists who not
only spared the time to discuss various points and
to send me numerous reprints of their work but,
perhaps more importantly, offered their encour-
agement, and convinced me that this book would
really meet a need. I am also very grateful for
access to the library at the MRC Human
Genetics Unit in Edinburgh. Many people have
generously supplied illustrations for the book
and, although they are acknowledged individu-
ally in the figure legends, I should like to thank
them again here. The study of chromosomes
includes strong visual and aesthetic elements as
well as scientific aspects, and no book on chro-
mosomes could be produced without being gen-
erously illustrated. I hope that the result will not
merely describe the state of chromosomology at
the beginning of the twenty-first century but
also, by highlighting lacunae in our knowledge,
stimulate further research into chromosomes.
Adrian T. Sumner
North Berwick
January 2002