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Fundamental Genetics
John Ringo
University of Maine

iii

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PUBLISHED BY THE PRESS SYNDICATE OF THE UNIVERSITY OF CAMBRIDGE

The Pitt Building, Trumpington Street, Cambridge, United Kingdom

CAMBRIDGE UNIVERSITY PRESS

The Edinburgh Building, Cambridge CB2 2RU, UK

40 West 20th Street, New York, NY 10011-4211, USA
477 Williamstown Road, Port Melbourne, VIC 3207, Australia
13, 28014 Madrid, Spain
Ruiz de Alarcon
Dock House, The Waterfront, Cape Town 8001, South Africa
http://www.cambridge.org

C

John Ringo 2004

This book is in copyright. Subject to statutory exception

and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.
First published 2004
Printed in the United States of America
Typeface Swift 10/14 pt. and Gill Sans

System LATEX 2 [TB]

A catalog record for this book is available from the British Library.
Library of Congress Cataloging in Publication Data
Ringo, John, 1943Fundamental genetics / John Ringo.
p.

cm.

Includes bibliographical references and index.

ISBN 0-521-80934-7 (hb) -- ISBN 0-521-00633-3 (pbk.)
1. Genetics. I. Title.
QH430.R55 2003
576.5--dc21
ISBN 0 521 80934 7 hardback
ISBN 0 521 00633 3 paperback

2003048463

iv

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Contents

Preface
Acknowledgments

Chapter 1 Life Forms and Their Origins

page xi
xiii
1

Chapter 2 Nucleic Acids

10

Chapter 3 Proteins

18

Chapter 4 Simple Chromosomes

26

Chapter 5 Chromosomes of Eukarya

34

Chapter 6 Genome Content

43

Chapter 7 RNA Synthesis 1: Transcription

52

Chapter 8 RNA Synthesis 2: Processing

65

Chapter 9 Abundance of RNAs in Bacteria

74

Chapter 10 Abundance of RNAs in Eukarya

85

Chapter 11 Protein Synthesis

96

Chapter 12 DNA Replication

107

Chapter 13 Chromosome Replication

115

Chapter 14 Molecular Events of Recombination

124

Chapter 15 Micromutations

136

Chapter 16 Repair of Altered DNA

145

Chapter 17 Reproduction of Bacteria

153

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CONTENTS

Chapter 18 Horizontal Gene Transfer in Bacteria

161

Chapter 19 Cell Cycles of Eukarya

172

Chapter 20 Meiosis

182

Chapter 21 Chromosomal Abnormalities

191

Chapter 22 Life Cycles of Eukarya

201

Chapter 23 Reproduction of Viruses

213

Chapter 24 Genetic Processes in Development

222

Chapter 25 Sex Determination and Dosage

Compensation

236

Chapter 26 Cancer

247

Chapter 27 Cutting, Sorting, and Copying DNA

254

Chapter 28 Genotyping by DNA Analysis

265

Chapter 29 Genetically Engineered Organisms

271

Chapter 30 Genomics

280

Chapter 31 Behavior of Genes and Alleles

290

Chapter 32 Probability and Statistics Toolkit

302

Chapter 33 Genes, Environment, and Interactions

315

Chapter 34 Locating Genes

326

Chapter 35 Finding and Detecting Mutations

338

Chapter 36 Cytoplasmic Inheritance

349

Chapter 37 Genetic Variation in Populations

359

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CONTENTS

Chapter 38 Mutation, Migration, and Genetic Drift

366

Chapter 39 Natural Selection

374

Chapter 40 Quantitative Genetics

383

Chapter 41 Speciation

395

Chapter 42 Molecular Evolution and Phylogeny

402

Glossary
Index

409
451

ix

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Chapter 1

Life Forms and Their Origins

Overview
This chapter introduces several basic genetic concepts, without
going into detail about any of them. These genetic concepts are
as follows:
r
r
r
r

life form
nucleic acid
gene
chromosome

r
r

organism
virus
semiautonomous organelle

The origin of life and the evolution of the three domains of life
are described briey.

Life Forms Are Genetic Systems

Two essential components of every life form are proteins and nucleic acids. Nucleic acids (DNA and RNA) are thread-like coding
molecules, the building material of genes and chromosomes. Genetics is about genes and chromosomes their structure and function, their behavior and misbehavior, their evolution, and methods of studying them. Because genes are the coding molecules of
life, they are complicated and varied. It is difcult to pin down the
term gene in a simple denition, but, to a rst approximation,
a gene is a segment of nucleic acid whose immediate function
is to encode a piece of RNA (Figure 1.1). The key concepts here
are replication (copying) of genes and coding. The replication of
genes and their coding properties are described in detail in later
chapters.

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F U N DA M E N TA L G E N E T I C S

Genes replicate and

code for RNA. For most
genes, the final gene product
is protein.

Fig 1.1

GENE

RNA

PROTEIN

Replication

From a genetic point of view, a life form is an assemblage

of large molecules capable of reproducing itself and including
at least one chromosome. A chromosome is a long, thin thread
made of DNA or, in some cases, RNA and may also contain proteins. To qualify as a chromosome, a nucleic acid molecule must
contain one or more genes, be replicated faithfully in a regulated
manner, and be transmitted from a life form to its descendants
in a reproductive cycle. Not every molecule of nucleic acid is a
chromosome, even if it contains genes. The nucleic acid part of a
life forms set of chromosomes is its genome.
All life forms arise from preexisting life forms via a reproductive cycle during which chromosomes are copied and the copies
are passed on from parent to progeny (Figure 1.2). According to
this broad, genetically based denition, life forms include organisms (cellular forms), viruses, mitochondria, and chloroplasts.
This book concentrates on the genetics of organisms.

Organisms
Organisms are made of cells, membrane-bound structures capable
of reproduction, growth, and metabolism. The genome of a cell
encodes all the proteins required for that cells survival. Every cell
has at least one chromosome, which is made of DNA and proteins.
Cells also have many ribosomes, micromachines for synthesizing
proteins. A membrane surrounds every cell. In some organisms,
the cell envelope includes a cell wall and one or more additional
membranes. An organism can be a single cell or many cells joined
together.
Organisms comprise three major divisions or domains: Bacteria, Archaea, and Eukarya (Figure 1.3). The compelling genetic
evidence for this broad taxonomic division comes from DNA sequences of slowly evolving genes. Despite their genetic and biochemical differences, bacterial and archaeal cells are morphologically similar: they lack nuclei, and they reproduce asexually, by
simple cell division. Little is known about the genetics of archaea.

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LIFE FORMS AND THEIR ORIGINS

Above: Stained
chromosomes of a normal
female human, from a cell
nearing division. Below: The
same 46 chromosomes
rearranged into numbered
pairs, the karyotype.
Photograph by Dr. Laurent
Beauregard, Genetics
Department, Affiliated
Laboratory, Inc., Bangor,
Maine.

Fig 1.2

13

14

15

19

20

21

10

11

12

16

17

18

22

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F U N DA M E N TA L G E N E T I C S

Cell envelope:
1 membrane
wall in some cases

Nucleolus

Endoplasmic
reticulum

Chromosome
in nucleoid region
Plasmids

Nucleus
Thread-like
chromosomes
Centrosome

Flagella

Ribosomes
Cell envelope:
1 or 2 membranes
& usually a wall

Pili
Ribosomes

Bacterium or Archaeon

A quick look at two

kinds of cell.

Fig 1.3

Mitochondrion

Eukaryon

In contrast to bacteria and archaea, eukaryal cells possess

membrane-bound nuclei, an internal system of membranes, and
a cytoskeleton made of microtubules.

The Origin of Life

From the time the earth began to form, 4.6 109 years (4600 Ma =
megaanum, or million years) ago, until it cooled sufciently for
liquid water to exist on its surface, 4400 to 4200 Ma ago, the
temperature was too high for life to exist. Meteorites bombarded
early earth, and some geophysicists believe these ocean-vaporizing
impacts likely did not abate sufciently for life to emerge until
4200 to 4000 Ma ago (Figure 1.4). The 12 C:13 C ratio of organic
carbon is higher than that of inorganic carbon. This isotopic ratio
in fossils of the most ancient sediments known suggests that life
was abundant 3900 Ma ago or a bit earlier; sedimentary apatite
4.6

Time line of earths

history. The times given for
biological firsts are very
approximate.

Fig 1.4

Life
Earth
begins
forms
Liquid
water
Meteoric
bombardment
ends

3
First
fossils

First
eukarya

First
animals

Billions of years ago

0
First
primates

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LIFE FORMS AND THEIR ORIGINS

(a mineral consisting of calcium phosphates) is a biomarker rst

appearing in large amounts 3800 Ma ago. The implications are
remarkable: life emerged from non-life during a period lasting
only 100 to 300 Ma.
Fundamental organic molecules required for life (e.g., amino
acids and nucleotides) are thought to have originated through
natural chemical reactions starting with simple molecules such
as methane, ammonium, phosphate, and water, with the energy
for the reactions being heat and electrical discharges in the atmosphere. Modern experiments have shown these reactions to be
feasible. Also, under realistic conditions not involving enzymes,
amino acids polymerize into polypeptides and nucleotides polymerize into nucleic acids.

The First Organisms: RNA-Based?

All living organisms have genes made of DNA, which code for RNA.
RNA molecules are intermediate coding molecules in the synthesis of proteins, which make important structures of the cell and
carry out virtually all the metabolic functions (Figure 1.5). According to one theory, the original life forms used RNA for coding
and for metabolic functions. Some RNAs act as enzymes; these
are ribozymes. Biochemists are nding many chemical reactions
that are catalyzed by RNAs. If ancient proto-organisms possessed
RNAs capable of directing the synthesis of more copies of RNA
molecules, then both genes and enzymes could have been made
of RNA in those ancient times, perhaps between 4000 and 3500 Ma
ago. In this RNA world RNA served double duty: genes and
enzymes.
The ancestral cells or protocells had evolved into bacteria-like
cells by 3500 Ma ago; fossil cells that resemble bacteria were
very abundant by then. The split between archaea and bacteria occurred between 3500 and 1900 Ma ago, and the eukaryaarchaea split probably occurred between 1900 and 1500 Ma ago
Functional
product
+

Some RNAs can

both cut themselves and ligate
the pieces.

Fig 1.5

Degraded

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F U N DA M E N TA L G E N E T I C S

Evolutionary tree of
three domains of life. Each line
is a major taxonomic lineage.

Fig 1.6

Bacteria

Archaea

Eukarya
Animals

Ancestral
life

(Figure 1.6). The eukarya are enormously diverse; taxonomists classify them into a stupefyingly detailed and complex hierarchy of
taxa.

Mitochondria and Chloroplasts:

Semiautonomous Organelles
Eukaryal cells contain several organelles or mini-organs inside
the cell. Two important membrane-bound organelles found in
many eukarya are the mitochondrion [pl., mitochondria] and the
chloroplast. Their main functions are oxidative metabolism (mitochondria) and photosynthesis (chloroplasts). They evolved from
purple bacteria and cyanobacteria, respectively (Figure 1.7). The
ancestral bacteria became mutualistic endosymbionts in eukaryal

Purple
bacterium
2 billion years ago

Evolution of
mitochondria.

Fig 1.7

Ancestral
eukaryon

Many genes
moved from
guest to host

Mitochondrion

Modern
eukaryon

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LIFE FORMS AND THEIR ORIGINS

cells, meaning that both the host cell and the life form that living
inside it beneted. Mutualistic endosymbiosis is not rare. However, in these cases, the now-organelles have clearly lost their status as bacterial cells, for genes in the host eukaryons nucleus
encode many proteins of these organelles. Mitochondria and
chloroplasts are therefore genetically parasitic. On the other
hand, every mitochondrion and every chloroplast has its own
chromosome and its own protein-coding machinery. Furthermore,
mitochondria and plastids (chloroplasts and related organelles)
are unlike any other membrane-bound organelle, such as the nucleus: mitochondria and chloroplasts are never disassembled and
reassembled; instead, they reproduce by division, as did their ancestral bacteria.

Viruses, the Completely Acellular Life Forms

Viruses are acellular life forms: obligate intracellular parasites
possessing one or more chromosomes. During the infectious stage
of a viruss life cycle, the virus is a virion the viral genome encapsulated in a structure made of protein. Sometimes the virion
includes a membrane envelope stolen from the hosts cytoplasmic membrane (Figure 1.8). Most viruses are genetically parasitic,
relying on its host for enzymes used in genetic processes. Only
viruses with relatively large genomes code for many of the proteins required for their own reproduction. Viruses infect all three
domains of life and may be classied according to host, genetic
material, or phylogeny. An overall phylogeny of viruses is not appropriate, for viruses appear to have evolved independently many
times. Any phylogeny of viruses, except for closely related ones,
is difcult to establish, owing to rapid evolution and the tendency of viruses to acquire cellular genes. The going theory is

Bacterial viruses

HIV budding off host

cell membrane

Fig 1.8

particles.

Some infectious virus

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F U N DA M E N TA L G E N E T I C S

that virus genomes evolved from bits and pieces of their hosts
genomes.

A Few Odd Forms

Plasmids are small, nonessential, extra chromosomes of cells.
Plasmids code for proteins, including proteins useful to the cell
(e.g., genes conferring antibiotic resistance). Some plasmids move
between cells and may have genes encoding the machinery for
intercellular movement. Are plasmids life forms? Some say yes,
because plasmids are parasite-like, but I opt for the idea that plasmids are merely small, inessential chromosomes. Another category of DNA molecule with some of the basic properties of a life
form is the transposon. Transposons are sequences of DNA that
can move about the genome, within or between chromosomes;
transposons code for proteins that help them to move.
There are nucleic acid molecules that do not qualify as life
forms by the denition offered here but that some biologists do
consider living, or at least lifelike. These are viroids and virusoids, small circular RNA molecules that do not code for protein.
Viroids are parasites of plants and cause signicant economic
damage. Virusoids are parasites of viruses.
The strangest of all life-oid things is the prion, an infectious
protein that can cause the modication of similar proteins in a
cell, ultimately leading to the cells death. Prions cause certain
slow, infectious, neurological diseases, including bovine spongiform encephalopathy (mad cow disease).

Most of Genetics Is Based on a Restricted

Sample of Organisms
There are over 10 million species in the three domains of life.
Much of what is known about the genetics of cellular organisms
has been learned from intensive study of a limited sample of
species clustered in a few branches of the evolutionary tree of organisms, most prominently two bacteria (Escherichia coli and Bacillus subtilis), a few fungi (notably the mold Neurospora crassa and the
bread yeast Saccharomyces cervisiae), two owering plants (Zea mays
and Arabidopsis thaliana), and four animals (the fruit y Drosophila

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LIFE FORMS AND THEIR ORIGINS

melanogaster, the nematode Caenorhabditis elegans, the mouse Mus

musculus, and Homo sapiens). Important genetic phenomena have
been substantially investigated in hundreds of other species of
bacteria, fungi, plants, animals, and ciliates, as well as in many
viruses only viral species, though, that infect bacteria or multicellular/multinucleate eukarya. The most conspicuous and troubling gaps in knowledge of basic genetics occur in the archaea and
in the early-branching taxa of eukarya troubling, because we
have no idea how large those gaps may be. Fortunately, straightforward analysis of DNA sequences is beginning to allow us to
infer a great deal about the genetics of these organisms.

Further Reading
Gesteland RF, Cech T, Atkins JF. 1999. The RNA World, 2nd ed., Cold Spring
Harbor Laboratory Press, Cold Spring Harbor, NY.
Gray MW. 1999. Evolution of organellar genomes. Curr. Opin. Genet. Dev.
9:678687.
Holland HD. 1997. Evidence for life on earth more than 3850 million
years ago. Science 275:3839.
Lazcano A, Miller SL. 1996. The origin and early evolution of life. Cell
85:793798.
Levine A. 1991. Viruses. WH Freeman, New York.
Woese CR, Kandler O, Wheelis ML. 1990. Towards a natural system of
organisms: Proposal for the domains Archaea, Bacteria, and Eucarya.
Proc. Natl. Acad. Sci. USA 87:45764579.