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ISBN 9780815345084
Library of Congress Cataloging-in-Publication Data
Names: Brown, T. A. (Terence A.), author. Title: Genomes 4 / Terry Brown. Other titles: Genomes | Genomes four
Description: 4th. | New York, NY : Garland Science, [2017] | Preceded by: Genomes 3 / T. A. Brown. 3rd ed. New York : Garland Science, c2007. | Includes bibliographical references and index.
Identifiers: LCCN 2017013507 | ISBN 9780815345084 (alk. paper)
LC record available at https://lccn.loc.gov/2017013507
About the Author
I became fascinated with the natural world when I was very young. I began my research career studying the effects of metal pollution on microorganisms and the tolerance that some plants display to high concentrations of toxic metals. I then became excited by DNA and worked on mitochondrial genes in fungi in order to learn the new (in those days) techniques for gene cloning and DNA sequencing. I contributed to the discovery of mitochondrial introns and to work that described the base-paired structure of these introns. I then became interested in ancient DNA and was one of the first people to carry out DNA extractions with bones and preserved plant remains. This work has required close collaboration with archaeologists, and has led to my current interests in paleogenomics, the origins of agriculture, and the evolution of domesticated plants.
I obtained my PhD from University College London in 1977 and then worked in New York, Oxford, Colchester, and Manchester before beginning in 1984 as a Lecturer in Biotechnology at the University of Manchester Institute of Science and Technology (UMIST). I was appointed Professor of Biomolecular Archaeology in 2000 and was Head of Biomolecular Sciences at UMIST from 2002–2004. I was then Associate Dean in the Faculty of Life Sciences of the University of Manchester until 2006, before taking a break from administration in order to have more time to do research.
My other undergraduate textbooks include Introduction to Genetics, A Molecular Approach (Garland Science).
Published by Garland Science, Taylor & Francis Group, LLC, an informa business, 711 Third Avenue, New York, NY 10017, USA, and 2 Park Square, Milton Park, Abingdon, OX14 4RN, UK.
Printed in the United States of America
15 14 13 12 11 10 9 8 7 6 5 4 3 2 1
PREFACE
There have been remarkable advances in our knowledge of genomes since the previous edition of this book was published ten years ago. Back in 2007, next-generation sequencing was in its infancy and high-throughput methods for transcriptomics and proteomics were only beginning to be exploited. The application of these methods over the last ten years has resulted in an exponential increase in the number of species for which genome sequences and annotations are now available, and has enabled multiple versions of the genome of a single species to be examined. The profusion of new sequences has had a particularly dramatic impact on bacterial genomics, with introduction of the pan-genome concept and the discovery of extensive lateral transfer of genes between species. Our knowledge of eukaryotic genomes has undergone equally dramatic change, with the discovery of new types of noncoding RNA, including the vast numbers of long RNAs that are transcribed from the supposedly intergenic regions of many genomes.
Genomes 4 retains the overall structure of the previous editions, with the book divided in four parts, on genome sequencing and annotation, genome anatomies, genome expression, and genome replication and evolution. With some small changes, the order of chapters remains unchanged. However, the text throughout has been completely updated and, in many chapters, substantially revised. In particular, the development of transcriptomics and proteomics has reached the point where in Genomes 4 it is possible to describe the processes of transcription and translation from a genomewide perspective, rather than simply through an examination of the expression of individual genes. This was my aim when I wrote the first edition of Genomes way back in 1999, but the information available at that time meant that these core chapters were fairly orthodox treatments of gene rather than genome expression. We are still some way from being able to describe the entire expression of a genome as a single integrated process, but we are getting there and I hope that in Genomes 4 I have been able to convey to the reader at least some aspects of the joined-up nature of genome expression.
Genomes 4 has been a long time in the making and I would like to thank Liz Owen of Garland Science for her continued enthusiasm for the book and her gentle reminders about approaching deadlines. I also wish to thank David Borrowdale and Georgina Lucas at Garland for managing the production of the book, and Matthew McClements for his splendid artwork. As with the previous editions, Genomes 4 would not have been finished without the support of my wife, Keri. The acknowledgment in the first edition that “if you find this book useful then you should thank Keri, not me, because she is the one who ensured that it was written” is equally true for the fourth edition.
A N OTE TO T h E R EA d ER
I have tried to make the fourth edition of Genomes as user friendly as possible. The book therefore includes a number of devices intended to help the reader and to make the book an effective teaching and learning aid.
Organization of the Book
Genomes 4 is divided into four parts:
Part I – Studying Genomes begins with an orientation chapter that introduces the reader to genomes, transcriptomes, and proteomes, and then in Chapter 2 moves on to the methods, centered on PCR and cloning, that were used in the pre-genome era to examine individual genes. The techniques that are used for constructing genetic and physical maps, which are still important in many genome projects, are then described in Chapter 3, followed in Chapter 4 by the methodology for obtaining DNA sequences and assembling reads into draft and finished genomes sequences. Two chapters are then devoted to analysis of genome sequences: Chapter 5 on the annotation of a genome by identification of genes and other features, and Chapter 6 on functional analysis of the genes that are discovered.
Part II – Genome Anatomies surveys the anatomies of the various types of genome that are found on our planet. Chapter 7 covers eukaryotic nuclear genomes, with emphasis on the human genome, partly because of the importance of the human genome in so many areas of research, but also because our genome is the best studied of all those for which sequences are available. Chapter 8 deals with the genomes of prokaryotes and of eukaryotic organelles, the latter included here because of their prokaryotic origins, and Chapter 9 describes viral genomes and mobile genetic elements, these being grouped together because some types of mobile element are related to viral genomes.
Part III – How Genomes are Expressed describes how the biological information contained in a genome is utilized by the cell within which that genome resides. Chapter 10 addresses the important issue of how the packaging of DNA into chromatin affects expression of different parts of the genome, and Chapter 11 then describes the central role that DNA-binding proteins play in expressing those parts of the genome that are active at a particular time. Chapter 12 moves on to the transcriptome, describing how transcriptomes are studied, their compositions, and how a cell’s transcriptome is synthesized and maintained. Chapter 13 gives an equivalent description of proteomics and the proteome, and Chapter 14 concludes this part of the book by exploring how the genome acts within the context of the cell and organism, responding to extracellular signals and driving the biochemical changes that underlie differentiation and development.
Part IV – How Genomes Replicate and Evolve links DNA replication, mutation, and recombination with the gradual evolution of genomes over time. In Chapters 15–17 the molecular processes responsible for replication, mutation, repair, and recombination are described, and in Chapter 18 the ways in which these processes are thought to have shaped the structures and genetic contents of genomes over evolutionary time are considered. Chapter 18 then ends with a small number of case studies to illustrate how molecular phylogenomics and population genomics are being used in research and biotechnology.
L EARN i NG Aid S
Each chapter has a set of Short Answer Questions and In-Depth Problems, as well as an annotated Further Reading list. At the end of the book there is an extensive Glossary.
Short answer questions require 50- to 500-word answers. The questions cover the entire content of each chapter in a fairly straightforward manner, and most can be marked simply by checking each answer against the relevant part of the text. A student can use the short answer questions to work systematically through a chapter, or can select individual ones in order to evaluate their ability to answer questions on specific topics. The short answer questions could also be used in closed-book tests.
In-depth problems require a more detailed answer. They vary in nature and in difficulty, the simplest requiring little more than a literature survey, the intention of these particular problems being that the student advances his or her learning a few stages from where Genomes 4 leaves off. Other problems require that the student evaluates a statement or a hypothesis, based on their understanding of the material in the book, possibly supplemented by reading around the subject. These problems will, hopefully, engender a certain amount of thought and critical awareness. A few problems are difficult, in some cases to the extent that there is no solid answer to the question posed. These are designed to stimulate debate and speculation, which stretches the knowledge of each student and forces them to think carefully about their statements. The in-depth problems can be tackled by students working individually, or alternatively can form the starting point for a group discussion.
Further Reading lists at the end of each chapter include those research papers, reviews, and books that I look on as the most useful sources of additional material. My intention throughout Genomes 4 has been that students should be able to use the reading lists to obtain further information when writing extended essays or dissertations on particular topics. Research papers are therefore included, but only if their content is likely to be understandable to the average reader of the book. Emphasis is also placed on accessible reviews, one strength of these general articles being the context and relevance that they provide to a piece of work. The reading lists are divided into sections reflecting the organization of information in the chapter, and in some cases I have appended a few words summarizing the particular value of each item to help the reader decide which ones he or she wishes to seek out. In some cases, Further Reading also includes URLs for databases and other online resources relevant to the material covered in a chapter.
The Glossary defines every term that is highlighted in bold in the text, along with a number of additional terms that the reader might come across when referring to books or articles in the reading lists. The glossary therefore provides a quick and convenient means by which the reader can remind themselves of the technical terms relevant to the study of genomes, and also acts as a revision aid to make sure those definitions are clearly understood during the minutes of uncertainty that many students experience immediately before an exam.
iNSTR uc TOR R ESO u R c ES
The images from the book are available through www.garlandscience.com in two convenient formats: PowerPoint® and JPEG. They have been optimized for display on a computer. Figures are searchable by figure number, by figure name, or by keywords used in the figure legend from the book. Help on answering the In-Depth Problems, found at the end of each chapter, is also available.
Ac KNOWLE d GMENTS
The Author and Publisher of Genomes 4 gratefully acknowledge the contribution of the following reviewers in the development of this edition.
David Baillie, Simon Fraser University; Linda Bonen, University of Ottawa; Hugh Cam, Boston College; Yuri Dubrova, University of Leicester; Bart Eggen, University of Groningen; Robert Fowler, San José State University; Sidney Fu, George Washington University; Adrian Hall, Sheffield Hallam University; Lee Hwei Huih, Universiti Tunku Abdul Rahman; Glyn Jenkins, Aberystwyth University; Julian M. Ketley, University of Leicester; Torsten Kristensen, University of Aarhus; Gerhard May, University of Dundee; Mike McPherson, University of Leeds; Isidoro Metón, Universitat de Barcelona; Gary Ogden, St. Mary’s University; Paul Overvoorde, Macalester College; John Rafferty, University of Sheffield; Andrew Read, University of Manchester; Joaquin Cañizares Sales, Universitat Politècnica de València; Michael Schweizer, Heriot-Watt University; Eric Spana, Duke University; David Studholme, Exeter University; John Taylor, University of Newcastle; Gavin Thomas, University of York; Matthew Upton, Plymouth University; Guido van den Ackerveken, Utrecht University; Vassie Ware, Lehigh University; Wei Zhang, Illinois Institute of Technology.
3.4 l i N k Age A NA lysis with Di FF e R e N t t ypes o F oR g AN isms 69
Linkage analysis when planned breeding experiments are possible 69
Gene mapping by human pedigree analysis 71
Genetic mapping in bacteria 73
The limitations of linkage analysis 74
3.5 p hysic A l mA ppi N g by Di R ect e xA mi NAtio N o F DNA m olecules 75
Conventional restriction mapping is applicable only to small DNA molecules 75
Optical mapping can locate restriction sites in longer DNA molecules 77
Optical mapping can be used to map other features in a DNA molecule 79
3.6 p hysic A l mA ppi N g by Assig N i N g
mAR ke R s to DNA F RAgme N ts 81
Any unique sequence can be used as an STS 81
DNA fragments for STS mapping can be obtained as radiation hybrids 82
A clone library can be used as the mapping reagent 83
s umm
4.1 c h A i N - t e R mi NAtio N s e Q ue N ci N g 87
Chain-termination sequencing in outline 87
Not all DNA polymerases can be used for sequencing 89
Chain-termination sequencing with Taq polymerase 90
Strengths and limitations of chain-termination sequencing 91
4.2 Next- g e N e RAtio N s e Q ue N ci N g
Preparation of a sequencing library is the common feature of next-generation methods 93
Various next-generation sequencing methods have been devised 95
Third- and fourth-generation methods enable sequencing in real time
4.3 h ow to s e Q ue N ce A g e N ome 98
The potential of the shotgun method was proven by the Haemophilus influenzae sequence 99
Many prokaryotic genomes have been sequenced by the shotgun method 100
Shotgun sequencing of eukaryotic genomes requires sophisticated assembly programs 102 More complex genomes can be sequenced by a hierarchical shotgun approach
What is a genome sequence and do we always need one?
The Human Genome Project: genome sequencing in the heroic age 109
The Neanderthal genome: assembly of an extinct genome by use of the human sequence as a reference 110
The giant panda genome: shotgun sequencing based entirely on next-generation data
111
The barley genome: the concept of gene space 113
umm ARy
5.1 g e N ome A NN otAtio N by compute R A NA lysis o F the DNA s e Q ue N ce
The coding regions of genes are open reading frames
Simple ORF scans are less effective with genomes of higher eukaryotes
Locating genes for noncoding RNA
Homology searches and comparative genomics give an extra dimension to gene prediction 123
5.2 g e N ome A NN otAtio N by A NA lysis
ipts
Hybridization tests can determine if a fragment contains transcribed sequences 125
Methods are available for precise mapping of the ends of transcripts 126
Exon–intron boundaries can also be located with precision 126
5.3 A NN otAtio N by g e N omewi D e RNA mA ppi N g
Tiling arrays enable transcripts to be mapped onto chromosomes or entire genomes
Transcript sequences can be directly mapped onto a genome
5.4 g e N ome bR owse R s
s umm
s ho R t A N
R Questio N s
iN - D epth pR oblems
Fu R the R Re AD i N g
CHAPTER 6
I DENTI f YING G ENE f u NCTION s 135
6.1 compute R A NA lysis o F g e N e Fu N ctio N 135
Homology reflects evolutionary relationships 135
Homology analysis can provide information on the function of a gene 136
Identification of protein domains can help to assign function to an unknown gene 137
Annotation of gene function requires a common terminology 138
6.2 Assig N i N g Fu N ctio N by g e N e iNActivAtio N AND o ve R exp R essio N 139
Functional analysis by gene inactivation 140
Individual genes can be inactivated by homologous recombination 140
Gene inactivation without homologous recombination 142
Gene overexpression can also be used to assess function 144
The phenotypic effect of gene inactivation or overexpression may be difficult to discern 145
6.3 uND e R stAND i N g g e N e Fu N ctio N by s tu D ies o F e xp R essio N pAtte RN AND pR otei N pR o D uct
Reporter genes and immunocytochemistry can be used to locate where and when genes are expressed
Directed mutagenesis can be used to probe gene function in detail
6.4 u si N g co N ve N tio NA l g e N etic A NA lysis to iD e N ti F y g e N e Fu N ctio N
Identification of human genes responsible for inherited diseases
Genomewide association studies can also identify genes for diseases and other traits
s ho R t A N swe R Questio N
CHAPTER 7
7.1 Nucle AR g e N omes A R e co N tA i N e
7.2 h ow A R e the g e N es A RRAN ge D i
CHAPTER 8
Operons are characteristic features of prokaryotic genomes 188
Prokaryotic genome sizes and numbers of genes vary according to biological complexity 189
Genome sizes and numbers of genes vary within individual species 190
Distinctions between prokaryotic species are further blurred by lateral gene transfer 192
Metagenomes describe the members of a community 194
8.3 e uk ARyotic oR g AN ell AR g e N omes 195
The endosymbiont theory explains the origin of organellar genomes 195
Most organellar genomes are circular 196
The gene catalogs of organellar genomes 197
s
CHAPTER 9
9.1 t he g e N omes o F bActe R ioph Ages AND e uk ARyotic v i R uses
Bacteriophage genomes have diverse structures and organizations
Replication strategies for bacteriophage genomes
Structures and replication strategies for eukaryotic viral genomes
Some retroviruses cause cancer
Genomes at the edge of life 209
9.2 m obile g e N etic e leme N ts
RNA transposons with long terminal repeats are related to viral retroelements
Some RNA transposons lack long terminal repeats 212 DNA transposons are common in prokaryotic genomes
DNA transposons are less common in eukaryotic genomes
s umm ARy
The nucleus has an ordered internal structure
The DNA content of a nondividing nucleus displays different degrees of packaging
The nuclear matrix is thought to provide attachment points for chromosomal DNA
Each chromosome has its own territory within the nucleus
Each chromosome comprises a series of topologically associated domains
Insulators mark the boundaries of topologically associated
of histones influences many nuclear
deacetylation represses active regions of the
Acetylation is not the only type of histone
repositioning also influences gene
DNA m o D i F ic Atio N AND g e N ome
silencing by DNA methylation
is involved in genomic imprinting and X
CHAPTER 11
11.1 m etho D s F o R s tu Dyi N
X-ray crystallography provides structural data for any
is used to study the structures of small
Gel
Protection assays pinpoint binding sites with greater accuracy 244
Modification interference identifies nucleotides central to protein binding 246
Genomewide scans for protein attachment sites 247
11.2 t he s peci A l Fe Atu R es o F
DNA- b i ND i N g pR otei N s 249
The helix–turn–helix motif is present in prokaryotic and eukaryotic proteins 249
Zinc fingers are common in eukaryotic proteins 250
Other nucleic acid-binding motifs 251
11.3 iN te RActio N betwee N DNA AND i ts b i ND i N g pR otei N s 252
Direct readout of the nucleotide sequence 252
The nucleotide sequence has a number of indirect effects on helix structure 253
Contacts between DNA and proteins 253
s umm ARy
s ho R t A N swe R Questio N s
iN - D epth pR oblems 256
Fu R the R Re AD i N g
CHAPTER 12 T RAN s CRIPTO m E s
12.1 compo N e N ts o F the tRAN sc R iptome 257
The mRNA fraction of a transcriptome is small but complex 257
Short noncoding RNAs have diverse functions 259
Long noncoding RNAs are enigmatic transcripts 260
Microarray analysis and RNA sequencing are used to study the contents of transcriptomes 262
12.2 s yN thesis o F the compo N e N ts o F the tRAN sc R iptome 263
RNA polymerases are molecular machines for making RNA 264
Transcription start points are indicated by promoter sequences
Synthesis of bacterial RNA is regulated by repressor and activator proteins
Synthesis of bacterial RNA is also regulated by control over transcription termination
Synthesis of eukaryotic RNA is regulated primarily by activator proteins
12.3 Deg RADAtio N o F th e
compo N e N ts o F the tRAN sc R iptome
Several processes are known for nonspecific RNA turnover
RNA silencing was first identified as a means of destroying invading viral RNA
MicroRNAs regulate genome expression by causing specific target mRNAs to be degraded
12.4 iNF lue N ce o F RNA pR ocessi N g o N the compositio N o F A
The splicing pathway for eukaryotic pre-mRNA introns
The splicing process must have a high degree of precision
Enhancer and silencer elements specify alternative
12.5 tRAN sc R iptomes i N Rese AR ch
analysis as an aid to genome
and the responses of plants
CHAPTER 13
13.1 s tu Dyi N g the compositio N o F A pR oteome
The separation stage of a protein profiling project
The identification stage of a protein profiling project
Comparing the compositions of two proteomes 299
Analytical protein arrays offer an alternative approach to protein profiling
13.2 iD e N ti F yi N g pR otei N s t h At iN te RAct with oN e A N othe R
Identifying pairs of interacting proteins
Identifying the components of multiprotein complexes
Identifying proteins with functional interactions
Protein interaction maps display the interactions within a proteome
13.3 s yN thesis AND Deg RADAtio N o F the compo N e N ts o F the pR oteome 308
Ribosomes are molecular machines for making proteins 308
During stress, bacteria inactivate their ribosomes in order to downsize the proteome 311
Initiation factors mediate large-scale remodeling of eukaryotic proteomes
The translation of individual mRNAs can also be regulated 313
Degradation of the components of the proteome 314
13.4 iNF lue N ce o F pR otei N pR ocessi N g o N the compositio N o F the pR oteome
The amino acid sequence contains instructions for protein folding
Some proteins are activated by proteolytic cleavage
Important changes in protein activity can be brought about by chemical modification
13.5 b eyo ND the pR oteome
The metabolome is the complete set of metabolites present in a cell
Systems biology provides an integrated description of cellular activity
s umm ARy
CHAPTER 14
14.1 t he Respo N se o F the g e N ome to e xte RNA l s ig NA ls
Signal transmission by import of the
Receptor
Some
transduction pathways have few steps
Some
transduction pathways have many steps
Some signal transduction pathways operate
Yeast mating types are determined by gene conversion events
Genome rearrangements are responsible for immunoglobulin and T-cell receptor diversity
Bacteriophage λ: a genetic switch enables a choice to be made between alternative developmental pathways
Bacillus sporulation: coordination of activities in two distinct cell types
Caenorhabditis elegans: the genetic basis of positional information and the determination of cell fate
Fruit flies: conversion of positional information into a segmented body plan
Homeotic selector genes are universal features of higher eukaryotic development
Homeotic genes also underlie plant
Meselson–Stahl experiment proved that replication is semiconservative
topoisomerases provide a solution to the topological problem
on the semiconservative theme
clearly defined in
in higher eukaryotes have been less easy to identify
have limitations that complicate genome
Okazaki fragments must be joined together to complete lagging-strand replication 370
15.4 t e R mi NAtio N o F g e N ome
Replic Atio N 372
Replication of the E. coli genome terminates within a defined region 373
Little is known about termination of replication in eukaryotes 374
Telomerase completes replication of chromosomal DNA molecules, at least in some cells 375
Telomere length is implicated in cell senescence and cancer 378
Drosophila has a unique solution to the end-shortening problem 379
15.5 Regul Atio N o F e uk ARyotic g e N ome Replic Atio N 380
Genome replication must be synchronized with the cell cycle 380
Origin licensing is the prerequisite for passing the G1–S checkpoint 380
Replication origins do not all fire at the same time 382
The cell has various options if the genome is damaged 383
s umm ARy
s ho R t A N swe R Questio N s
CHAPTER 16
16.1 t he cAuses o F m utAtio N s
Errors in replication are a source of point mutations 390
Replication errors can also lead to insertion and deletion mutations 391
Mutations are also caused by chemical and physical mutagens 394
16.2 RepA i R o F m utAtio N s AND othe R t ypes o F DNA DA m Age 398
Direct repair systems fill in nicks and correct some types of nucleotide modification 398
Base excision repairs many types of damaged nucleotide 399
Nucleotide excision repair is used to correct more extensive types of damage 401
Mismatch repair corrects replication errors 402
CHAPTER 17
Single- and double-strand breaks can be repaired 403 If necessary, DNA damage can be bypassed during genome replication 405 Defects in DNA repair
h omologous Recombi NAtio N
The Holliday and Meselson–Radding models for homologous recombination
The double-strand break model for homologous recombination
RecBCD
18.2 e volutio N o F iN c R e A si N gly complex g e N omes 434
Genome sequences provide extensive evidence of past gene duplications 434
A variety of processes could result in gene duplication 438
Whole-genome duplication is also possible 439
Smaller duplications can also be identified in the human genome and other genomes 442
Both prokaryotes and eukaryotes acquire genes from other species 444
Genome evolution also involves rearrangement of existing genes 445
There are competing hypotheses for the origins of introns 448
The evolution of the epigenome 449
18.3 g e N omes: t he lA st 6 m illio N ye AR s 450
The human genome is very similar to that of the chimpanzee 451
Paleogenomics is helping us understand the recent evolution of the human genome 452
18.4 g e N omes to DAy: Dive R sity i N p opul Atio N s
The origins of HIV/AIDS 454
The first migrations of humans out of Africa
The diversity of plant genomes is an aid in crop breeding
s
pARt i
stu Dyi N g ge N omes
Genomes, Transcrip Tomes, and p roT eomes
Life as we know it is specified by the genomes of the myriad organisms with which we share the planet. Every organism possesses a genome that contains the biological information needed to construct and maintain a living example of that organism. Most genomes, including the human genome and those of all other cellular life forms, are made of DNA (deoxyribonucleic acid), but a few viruses have RNA (ribonucleic acid) genomes. DNA and RNA are polymeric molecules made up of chains of monomeric subunits called nucleotides. Each molecule of DNA comprises two polynucleotides wound around one another to form the famous double helix, in which the two strands are held together by chemical bonds that link adjacent nucleotides into structures called base pairs
The human genome, which is typical of the genomes of all multicellular animals, consists of two distinct parts (Figure 1.1):
• The nuclear genome comprises approximately 3,235,000,000 base pairs of DNA, divided into 24 linear molecules, the shortest 48,000,000 base pairs in length and the longest 250,000,000 base pairs, each contained in a different chromosome. These 24 chromosomes consist of 22 autosomes and the two sex chromosomes, X and Y. Altogether, some 45,500 genes are present in the human nuclear genome.
• The mitochondrial genome is a circular DNA molecule of 16,569 base pairs, up to 10 copies of which are present in each of the energy-generating organelles called mitochondria. The human mitochondrial genome contains just 37 genes.
Each of the approximately 1013 cells in the adult human body has its own copy or copies of the nuclear genome, the only exceptions being those few cell types, such as red blood cells, that lack a nucleus in their fully differentiated state. The vast majority of cells are diploid and so have two copies of each autosome, plus two sex chromosomes, XX for females or XY for males—46 chromosomes in all. These are called somatic cells, in contrast to sex cells, or gametes, which are haploid and have just 23 chromosomes, one of each autosome and one sex chromosome. Each cell also has multiple copies of the mitochondrial genome: 2000–7000 copies in somatic cells, such as those in the liver and heart tissue, and over 100,000 copies in each female oocyte
1.1 DNA
1.2 RNA AND the tRAN sc R iptome
1.3 pR otei N s AND the pR oteome
The genome is a store of biological information, but on its own it is unable to release that information to the cell. Utilization of the biological information contained in the genome requires the coordinated activity of enzymes and other proteins, which participate in a complex series of biochemical reactions referred to as genome expression (Figure 1.2). The initial product of genome expression is the transcriptome, a collection of RNA molecules derived from those genes that are active in the cell at a particular time. The transcriptome is maintained by the process called transcription, in which individual genes are copied into RNA molecules. The second product of genome expression is the proteome, the cell’s repertoire of proteins, which specifies the nature of the biochemical reactions that the cell is able to carry out. The proteins that make up the proteome are synthesized by translation of some of the individual RNA molecules present in the transcriptome.
This book is about genomes and genome expression. It explains how genomes are studied (Part I), how they are organized (Part II), how they function (Part III), and how they replicate and evolve (Part IV ). It was not possible to write this book until quite recently. Since the 1950s, molecular biologists have studied individual genes or small groups of genes, and from these studies they have built up a wealth of knowledge about how genes work. But only during the last few years have techniques been available that make it possible to examine entire genomes. Individual genes are still intensively studied, but information about individual genes is now interpreted within the context of the genome as a whole. This new, broader emphasis applies not just to genomes but to all of biochemistry and cell biology. No longer is it sufficient simply to understand individual biochemical pathways or subcellular processes. The challenge now is provided by systems biology, which attempts to link together these pathways and processes into networks that describe the overall functioning of living cells and living organisms.
This book will lead you through our knowledge of genomes and show you how this exciting area of research is underpinning our developing understanding of biological systems. First, however, we must pay attention to the basic principles of molecular biology by reviewing the key features of the three types of biological molecule involved in genomes and genome expression: DNA, RNA, and protein.
1.1 DNA
DNA was discovered in 1869 by Friedrich Miescher, a Swiss biochemist working in Tübingen, Germany. The first extracts that Miescher made from human white blood cells were crude mixtures of DNA and chromosomal proteins, but the following year he moved to Basel, Switzerland (where the research institute
Figure 1.1 Nuclear and mitochondrial components of the human genome.
Human family
Human cell
Nuclear genome Mitochondrial genome
named after him is now located), and prepared a pure sample of nucleic acid from salmon sperm. Miescher’s chemical tests showed that DNA is acidic and rich in phosphorus and also suggested that the individual molecules are very large, although it was not until the 1930s, when biophysical techniques were applied to DNA, that the huge lengths of the polymeric chains were fully appreciated.
Genes are made of DNA
The fact that genes are made of DNA is so well known today that it can be difficult to appreciate that for the first 75 years after its discovery the true role of DNA was unsuspected. As early as 1903, W. S. Sutton had realized that the inheritance patterns of genes parallel the behavior of chromosomes during cell division, an observation that led to the chromosome theory, the proposal that genes are located in chromosomes. Examination of cells by cytochemistry, which makes use of stains that bind specifically to just one type of biochemical, showed that chromosomes are made of DNA and protein, in roughly equal amounts. Biologists at that time recognized that billions of different genes must exist and the genetic material must therefore be able to take many different forms. But this requirement appeared not to be satisfied by DNA, because in the early part of the twentieth century it was thought that all DNA molecules were the same. On the other hand, it was known, correctly, that proteins are highly variable, polymeric molecules, each one made up of a different combination of 20 chemically distinct amino acid monomers (Section 1.3). Genes simply had to be made of protein, not DNA.
The errors in understanding DNA structure lingered on, but by the late 1930s it had become accepted that DNA, like protein, has immense variability. The notion that protein was the genetic material initially remained strong but was eventually overturned by the results of two important experiments:
• Oswald Avery, Colin MacLeod, and Maclyn McCarty showed that DNA is the active component of the transforming principle, a bacterial cell extract that, when mixed with a harmless strain of Streptococcus pneumoniae, converts these bacteria into a virulent form capable of causing pneumonia when injected into mice (Figure 1.3A). In 1944, when the results of this experiment were published, only a few microbiologists appreciated that transformation involves transfer of genes from the cell extract into the living bacteria. However, once this point had been accepted, the true meaning of the Avery experiment became clear: bacterial genes must be made of DNA.
• Alfred Hershey and Martha Chase used radiolabeling to show that when a bacterial culture is infected with bacteriophages (also called phages, a type of virus), DNA is the major component of the bacteriophages that enters the cells (Figure 1.3B). This was a vital observation because it was known that, during the infection cycle, the genes of the infecting bacteriophages are used to direct synthesis of new bacteriophages, and this synthesis occurs within the bacteria. If only the DNA of the infecting bacteriophages enters the cells, then it follows that the genes of these bacteriophages must be made of DNA.
Although from our perspective these two experiments provide the key results that tell us that genes are made of DNA, biologists at the time were not so easily convinced. Both experiments have limitations that leave room for skeptics to argue that protein could still be the genetic material. For example, there were worries about the specificity of the deoxyribonuclease enzyme that Avery and colleagues used to inactivate the transforming principle. This result, a central part of the evidence for the transforming principle being DNA, would be invalid if, as seemed possible, the enzyme contained trace amounts of a contaminating protease and hence was also able to degrade protein. Neither is the bacteriophage experiment conclusive, as Hershey and Chase stressed when they published their results: “Our experiments show clearly that a physical separation of phage T2 into genetic and nongenetic parts is possible ... The chemical identification of the
Harmless bacteria
Mouse sur vives
Phage attached to bacteria
Agitate in blender
Harmless bacteria + transforming principle
Harmless bacteria + transforming principle treated with protease or ribonuclease
Mouse dies
dies
Centrifuge
Harmless bacteria + transforming principle treated with deox yribonuclease
Figure 1.3 the two experiments that suggested that genes are made of DNA. (A) Avery and colleagues showed that the transforming principle is made of DNA. The top two panels show what happens when mice are injected with harmless Streptococcus pneumoniae bacteria with or without addition of the transforming principle, a cell extract obtained from a virulent strain of S. pneumoniae. When the transforming principle is present, the mouse dies, because the genes in the transforming principle convert the harmless bacteria into the virulent form; these virulent bacteria subsequently were recovered from the lungs of the dead mouse. The lower two panels show that treatment with protease or ribonuclease has no effect on the transforming principle but that the transforming principle is inactivated by deoxyribonuclease.
(B) The Hershey–Chase experiment used T2 bacteriophages, each of which comprises a DNA molecule contained in a protein capsid attached
to a body and legs that enable the bacteriophage to attach to the surface of a bacterium and inject its genes into the cell. The DNA of the bacteriophages was labeled with 32P, and the protein was labeled with 35S. A few minutes after infection, the culture was agitated to detach the empty phage particles from the cell surface. The culture was then centrifuged, which collects the bacteria plus phage genes as a pellet at the bottom of the tube but leaves the lighter phage particles in suspension. Hershey and Chase found that the bacterial pellet contained 70% of the 32P-labeled component of the phages (the DNA) but only 20% of the 35S-labeled material (the phage protein). In a second experiment, not depicted here, Hershey and Chase showed that new phages produced at the end of the infection cycle contained less than 1% of the protein from the parent phages. For more details of the bacteriophage infection cycle, see Figure 2.27.
genetic part must wait, however, until some questions ... have been answered.” In retrospect, these two experiments are important not because of what they tell us but because they alerted biologists to the fact that DNA might be the genetic material and was therefore worth studying. This is what influenced Watson and Crick to work on DNA, and as we will see, it was their discovery of the doublehelix structure, which solved the puzzling question of how genes can replicate, that really convinced the scientific world that genes are made of DNA.
DNA is a polymer of nucleotides
The names of James Watson and Francis Crick are so closely linked with DNA that it is easy to forget that when they began their collaboration in October 1951, the detailed structure of the DNA polymer was already known. Their contribution was
Pellet of bacteria
Virulent bacteria
Mouse
Virulent bacteria
(A) The transforming principle
(B) The Hershey–Chase experiment
(A) A nucleotide
Figure 1.4 structure of a nucleotide. (A) General structure of a deoxyribonucleotide, which is the type of nucleotide found in DNA. (B) The four bases that occur in deoxyribonucleotides.
not to determine the structure of DNA per se but to show that in living cells two DNA chains are intertwined to form the double helix. First, therefore, we should examine what Watson and Crick knew before they began their work.
DNA is a linear, unbranched polymer in which the monomeric subunits are four chemically distinct nucleotides that can be linked together in any order in chains that are hundreds, thousands, or even millions of units in length. Each nucleotide in a DNA polymer is made up of three components (Figure 1.4):
• 2ʹ-Deoxyribose, which is a pentose, a type of sugar composed of five carbon atoms. These five carbons are numbered 1ʹ (spoken as one-prime), 2ʹ , and so on. The name 2ʹ-deoxyribose indicates that this particular sugar is a derivative of ribose, in which the hydroxyl (-OH) group attached to the 2ʹ-carbon of ribose has been replaced by a hydrogen (-H) group.
• A nitrogenous base, one of cytosine or thymine (single-ring pyrimidines) or adenine or guanine (double-ring purines). The base is attached to the 1ʹ-carbon of the sugar by a β-N-glycosidic bond attached to nitrogen number one of the pyrimidine or number nine of the purine.
• A phosphate group, comprising one, two, or three linked phosphate units attached to the 5ʹ-carbon of the sugar. The phosphates are designated α, β, and γ, with the α-phosphate being the one directly attached to the sugar.
A molecule made up of just the sugar and base is called a nucleoside; addition of the phosphates converts this to a nucleotide. Although cells contain nucleotides with one, two, or three phosphate groups, only the nucleoside triphosphates act as substrates for DNA synthesis. The full chemical names of the four nucleotides that polymerize to make DNA are
• 2ʹ-deoxyadenosine 5ʹ-triphosphate
• 2ʹ-deoxycytidine 5ʹ-triphosphate
• 2ʹ-deoxyguanosine 5ʹ-triphosphate
• 2ʹ-deoxythymidine 5ʹ-triphosphate
The abbreviations of these four nucleotides are dATP, dCTP, dGTP, and dTTP, respectively, or when referring to a DNA sequence, A, C, G, and T, respectively. In a polynucleotide, individual nucleotides are linked together by phosphodiester bonds between their 5
Figure 1.5 A short DNA polynucleotide showing the structure of the phosphodiester bond. Note that the two ends of the polynucleotide are chemically distinct.
of this linkage, we can see that the polymerization reaction (Figure 1.6) involves removal of the two outer phosphates (the β- and γ-phosphates) from one nucleotide and replacement of the hydroxyl group attached to the 3ʹ-carbon of the second nucleotide. Note that the two ends of the polynucleotide are chemically distinct, one having an unreacted triphosphate group attached to the 5ʹ-carbon (the 5ʹ - or 5ʹ-P terminus) and the other having an unreacted hydroxyl attached to the 3ʹ-carbon (the 3ʹ - or 3ʹ-OH terminus). This means that the polynucleotide has a chemical direction, expressed as either 5ʹ → 3ʹ (down in Figure 1.5) or 3ʹ → 5ʹ (up in Figure 1.5). An important consequence of the polarity of the phosphodiester bond is that the chemical reaction needed to extend a DNA polymer in the 5ʹ → 3ʹ direction is different from that needed to make a 3ʹ → 5ʹ extension. The DNA polymerase enzymes present in living organisms are only able to carry out 5ʹ → 3ʹ synthesis, which adds significant complications to the process by which doublestranded DNA is replicated (Section 15.3).
In the years before 1950, various lines of evidence had shown that cellular DNA molecules are composed of two or more polynucleotides assembled together in some way. The possibility that unraveling the nature of this assembly might provide insights into how genes work prompted Watson and Crick, among others, to try to solve the structure. According to Watson in his book The Double Helix, their work was a desperate race against the famous American biochemist Linus Pauling, who initially proposed an incorrect triple-helix model, giving Watson and Crick the time they needed to complete the double-helix structure. It is now difficult to separate fact from fiction, especially regarding the part played by Rosalind Franklin, whose X-ray diffraction studies provided the bulk of the experimental data in support of the double helix and who was herself very close to solving the structure. The one thing that is clear is that the double helix, discovered by Watson and Crick on Saturday, March 7, 1953, was the single most important breakthrough in biology during the twentieth century.
The discovery of the double helix can be looked on as one of the first multidisciplinary biological research projects. Watson and Crick used four quite different types of information to deduce the double-helix structure:
• Biophysical data of various kinds were used to infer some of the key features of the structure. The water content of DNA fibers was particularly important because it enabled the density of the DNA in a fiber to be estimated. The number of strands in the helix and the spacing between the nucleotides had to be compatible with the fiber density. Pauling’s triple-helix model was based on an incorrect density measurement that suggested that the DNA molecule was more closely packed than is actually the case.
• X-ray diffraction patterns (Section 11.1), most of which were produced by Rosalind Franklin, revealed the detailed helical structure (Figure 1.7).
• The base ratios, which had been discovered by Erwin Chargaff of Columbia University in New York, enabled the pairing between the polynucleotides in the helix to be deduced. Chargaff had carried out a lengthy series of chromatographic studies of DNA samples from various sources and showed
Figure 1.7 Franklin’s photo 51 showing the X-ray diffraction pattern obtained with a fiber of DNA. The cross shape indicates that DNA has a helical structure, and the extent of the shadowing within the diamond spaces above, below, and to either side of the cross show that the sugar–phosphate backbone is on the outside of the helix (see Figure 1.9). The positions of the various smears that make up the arms of the cross enable dimensions such as the diameter, rise per base pair, and pitch (see Table 1.1) of the molecule to be calculated. The missing smears (the gap in each arm of the cross, marked by the arrows) indicate the relative positioning of the two polynucleotides. These missing smears enabled Watson and Crick to recognize that there are two grooves of different depths on the outer surface of the helix (see Figure 1.9). (From Franklin R & Gosling RG [1953] Nature 171:740–741. With permission from Macmillan Publishers Ltd.)
Figure 1.6 the polymerization reaction that results in synthesis of a DNA polynucleotide. Synthesis occurs in the 5ʹ → 3ʹ direction, with the new nucleotide being added to the 3ʹ-carbon at the end of the existing polynucleotide. The βand γ-phosphates of the nucleotide are removed as a pyrophosphate molecule.
Purify the DNA
Mild acid treatment breaks phosphodiester bonds
Chromatography to quantify each nucleotide
Figure 1.8 the base ratio experiments performed by chargaff. DNA was extracted from various organisms and treated with acid to hydrolyze the phosphodiester bonds and release the individual nucleotides. Each nucleotide was then quantified by chromatography. The data show some of the actual results obtained by Chargaff. These indicate that, within experimental error, the amount of adenine is the same as that of thymine and the amount of guanine is the same as that of cytosine.
that although the values are different in different organisms, the amount of adenine is always the same as the amount of thymine and the amount of guanine equals the amount of cytosine (Figure 1.8). These base ratios led to the base-pairing rules, which were the key to the discovery of the double-helix structure.
• The construction of scale models of possible DNA structures, which was the only major technique that Watson and Crick performed themselves, enabled the relative positioning of the various atoms to be checked, to ensure that pairs that formed bonds were not too far apart and that other atoms were not so close together as to interfere with one another.
The double helix is stabilized by base pairing and base stacking
The double helix is right-handed, which means that if it were a spiral staircase and you were climbing upward, then the rail on the outside of the staircase would be on your right-hand side. The two strands run in opposite directions (Figure 1.9A). The helix is stabilized by two types of chemical interaction:
• Base pairing between the two strands involves the formation of hydrogen bonds between an adenine on one strand and a thymine on the other strand, or between a cytosine and a guanine (Figure 1.9B). Hydrogen bonds are weak electrostatic interactions between an electronegative atom (such as oxygen or nitrogen) and a hydrogen atom attached to a second electronegative atom. Hydrogen bonds are longer than covalent bonds and are much weaker; typical bond energies are 8–29 kJ mol–1 at 25°C, compared with up to 348 kJ mol–1 for a single covalent bond between a pair of carbon atoms. As well as their role in the DNA double helix, hydrogen bonds stabilize protein secondary structures. The two base-pair combinations—A base-paired with T and G base-paired with C—explain the base ratios discovered by Chargaff. These are the only pairs that are permissible, partly because of the geometries of the nucleotide bases and the relative positions of the atoms that are able to participate in hydrogen bonds, and partly because the pair must be between a purine and a pyrimidine: a purine–purine pair would be too big to fit within the helix, and a pyrimidine–pyrimidine pair would be too small.
• Base stacking involves attractive forces between adjacent base pairs and adds stability to the double helix once the strands have been brought together by base pairing. Base stacking is sometimes called π–π interactions, because it is thought to involve the p electrons associated with the double bonds of the purine and pyrimidine structures. However, this hypothesis is now being questioned, and the possibility that base stacking involves a type of electrostatic interaction is being explored.
Both base pairing and base stacking are important in holding the two polynucleotides together, but base pairing has added significance because of its biological implications. The limitation that A can only base-pair with T and G can only base-pair with C means that DNA replication can result in perfect copies of a parent molecule through the simple expedient of using the sequences of the preexisting strands to dictate the sequences of the new strands. This is templatedependent DNA synthesis, the system used by all cellular DNA polymerases
3‘ end Figure 1.9 Double-helix structure of DNA. (A) Two representations of the double helix. On the left, the structure is shown with the sugar–phosphate backbone of each polynucleotide drawn as a gray ribbon with the base pairs in green. On the right, the chemical structure for three base pairs is given. (B) A base-pairs with T, and G base-pairs with C. The bases are drawn in outline, with the hydrogen bonding indicated by dotted lines. Note that a G-C base pair has three hydrogen bonds whereas an A-T base pair has just two.
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(Section 2.1). Base pairing therefore enables DNA molecules to be replicated by a system that is so simple and elegant that as soon as the double-helix structure was publicized by Watson and Crick, every biologist became convinced that genes really are made of DNA.
The double helix has structural flexibility
The double helix described by Watson and Crick, and shown in Figure 1.9A , is called the B-form of DNA or B-DNA. Its characteristic features lie in its dimensions: a helical diameter of 2.37 nm, a rise of 0.34 nm per base pair, and a pitch (the distance taken up by a complete turn of the helix) of 3.4 nm, corresponding to 10 base pairs (bp)per turn. The DNA in living cells is thought to be predominantly in this B-form, but it is now clear that genomic DNA molecules are not entirely uniform in structure. This is mainly because each nucleotide in the helix has the flexibility to take up a slightly different molecular shape. To adopt these different conformations, the relative positions of the atoms in the nucleotide must change slightly. There are a number of possibilities but the most important conformational changes are as follows:
• Rotation around the β-N-glycosidic bond changes the orientation of the base relative to the sugar: the two possibilities are called the anti- and synconformations (Figure 1.10A). Base rotation influences the positioning of the two polynucleotides.
Figure 1.10 changes in nucleotide configuration that can affect the conformation of the double helix. (A) Structures of anti- and syndeoxyadenosine. The two structures differ in the orientation of the base relative to the sugar component of the nucleoside; rotation around the β-N-glycosidic bond converts one form into the other. The three other nucleosides also have antiand syn-conformations. (B) Sugar pucker, illustrating the positioning of the sugar carbons in the C2ʹ -endo- and C3ʹ -endoconfigurations.
• Sugar pucker refers to the three-dimensional shape of the sugar. The ribose component of the nucleotide does not have a planar structure: when it is viewed from the side, one or two of the carbon atoms are either above or below the plane of the sugar (Figure 1.10B). In the C2ʹ -endo-configuration, the 2ʹ-carbon is above the plane and the 3ʹ-carbon is slightly below, and in the C3ʹ -endo-configuration, the 3ʹ-carbon is above the plane and the 2ʹ-carbon is below. Because the 3ʹ-carbon participates in the phosphodiester bond with the adjacent nucleotide, the two pucker configurations have different effects on the conformation of the sugar–phosphate backbone.
Conformation changes resulting from rotation around the β-N-glycosidic bond and sugar pucker can give rise to major changes in the overall structure of the helix. It has been recognized since the 1950s that changes in the dimensions of the double helix occur when fibers containing DNA molecules are exposed to different relative humidities. For example, the modified version of the double helix called A-DNA has a diameter of 2.55 nm, a rise of 0.23 nm per base pair, and a pitch of 2.5 nm, corresponding to 11 base pairs per turn (Table 1.1). Like the B-form, A-DNA is a right-handed helix and the bases are in the anti-conformation relative to the sugar. The main difference lies with the sugar pucker: the sugars in the B-form are in the C2ʹ -endo-configuration, and those in A-DNA are in the C3ʹendo-configuration. Other right-handed variations of the double helix include Bʹ -, C-, Cʹ -, Cʹʹ-, D-, E-, and T-DNAs.
A more drastic reorganization is also possible, leading to the left-handed Z-DNA, in which the sugar–phosphate backbone adopts an irregular zigzag conformation. Z-DNA is a more tightly wound version of the double helix with 12 bp per turn and a diameter of only 1.84 nm (Table 1.1). It is known to occur in regions of a double helix that contain repeats of the motif GC (that is, the sequence of each strand is ...GCGCGCGC...). In these regions, each G nucleotide has the syn- and C3ʹ -endo-conformations and each C has the anti- and C2ʹ -endo-conformations.
Number of base pairs per turn 11 10 12 Base orientation
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the other; but they stand well-breathed on the summit, while their comrades are panting at the halfway station. One must not swerve to the right or left, but, setting his face toward duty, like Marcus Curtius who rode to death in the Roman Forum, he must push forward, with an honest ambition to reach the goal of success. It is not always the boy of aristocratic birth, wealthy parentage or social standing that wins the world’s laurels, but usually those boys who are unfortunately situated, who hew their way in the world instead of having it laid out and smoothed for them.
One of our Presidents, when asked what was his coat-of-arms, remembering that he had been a chopper of wood in his youth, replied, “A pair of shirt-sleeves.” Lord Tenterden was proud to point out to his son the shop in which his father had shaved for a penny. A French doctor once taunted Flechier, bishop of Nimes, who had been a tallow-chandler in his youth, with the meanness of his origin, to which Flechier replied, “If you had been born in the same condition that I was, you would still have been a maker of candles.”
Where is the boy with nobility of soul and purpose, who, though poor, is not tidy; who, being of humble origin, is not industrious; who, ridiculed by others, is not kind; and who, cramped by circumstances, is not heroic? That boy will rise to honor and fill an important place in life. He, like other boys of this country, may be a star rather than a flashing meteor in the realm of society.
ASPIRING BOYS.
From a farm to the Presidential chair seems a long distance, but Abraham Lincoln traveled it, and left behind him a name and reputation never to die. Andrew Johnson began life as a tailor and subsequently rose to be the chief officer of the nation. George Peabody was an apprentice in a country store, and ended as a millionaire philanthropist. Cyrus W. Field was in early life a clerk, but the world is indebted to him for the successful completion of the Atlantic cable. Samuel F. B. Morse, from an artist, became the inventor of the electric telegraph. Charles Dickens, the great novelist, began life as a newspaper reporter. Levi P. Morton was a clerk, John Wanamaker a messenger-boy, Lyman J. Gage a night-watchman and
James Whitcomb Riley a wandering sign-painter. The record, instead of being in the tens, could be increased to thousands of statesmen, governors, generals, business and professional men who have risen from the farm, the shop, the store, to important offices within the nation’s gift. There is no reason why a boy cannot make his way in the world. He may not be President, or banker, or lawyer, but he can fill an honorable position. He may be a master mechanic, a model business man, a useful educator, if he is willing to begin at the lowest round in the ladder, namely, neatness.
Boys are men of a smaller growth, and if they fail to cultivate selfrespect, it means the blighting of manhood, the ostracism of society, and the closing of the gate of opportunities to success. Self-respect is a robe with which every boy should clothe himself. It lies at the root of all virtues. It begets a stability of character, is the sentinel of the soul as the eyelid of the eye, and the corner-stone of all virtues.
NEATNESS SHOWS ITSELF BY CLEANLINESS.
There is no need in this day and country for a boy to go around with dirty face and hands. It is injurious to health, unbecoming and repulsive to any self-respecting person. On the other hand from
“The body’s purity, the mind Receives a secret, sympathetic aid.”
When Isaac Hopper, the Quaker, met a boy with dirty face or hands, he would stop him, and inquire if he ever studied chemistry. The boy, with a wondering stare, would answer, “No.” “Well then, I will teach thee how to perform a curious chemical experiment. Go home, take a piece of soap, put it in water, and rub briskly on thy hands and face. Thou hast no idea what a beautiful froth it will make, and how much whiter thy skin will be. That’s a chemical experiment; I advise thee to try it.” There is great virtue in soap and water vigorously applied, which doubtless gave rise to the old adage, “Cleanliness is next to godliness,” for virtue never dwells long with filth. An eminent man said, “I believe there never was a person scrupulously attentive to cleanliness who was a consummate villain.”
The singing birds are remarkable for the neatness and cleanliness of their plumage. The gay and cheerful animals of the fields avoid filth, and are usually of a clean appearance. The beauty and fragrance of the flowers owe all to this characteristic, and so also does the boy who is bright, intelligent, moral and ambitious. You will not find his finger nails long, but carefully trimmed and devoid of dirt, his ears and neck will be spotless, and his teeth clean and white like “drops of snow in banks of pretty pink roses.”
NEATNESS IN DRESS.
Self-respect will also show itself in neatness of dress. “It has,” says Barrington, “a moral effect upon the conduct of mankind. Let any gentleman find himself with dirty boots, soiled neck-cloth, and a general negligence of dress, he will, in all probability, find a corresponding disposition by negligence of address.” To be tidy does not mean to have costly attire. It is no mark of neatness for a boy to deck his fingers with rings, to sport a gold-headed cane, to wear flashy neck-wear, to have a bouquet of flowers on the lapel of his coat, for while these are not unbecoming in themselves, they give the impression of that sin which overthrew the angels, pride.
Dean Swift was an enemy of extravagance in dress, and particularly of that destructive ostentation in the middle classes, which led them to make an appearance above their condition in life. Of his mode of reproving this folly in those persons for whom he had an esteem, the following instance has been recorded:
When George Faulkner, the printer, returned from London, where he had been soliciting subscriptions for his edition of the Dean’s works, he went to pay his respects to him, dressed in a lace waistcoat, a big wig and other fopperies. Swift received him with the same ceremonies as if he had been a stranger. “And pray, sir,” said he, “what can be your commands with me?” “I thought it was my duty, sir,” replied George, “to wait on you immediately on my arrival from London.” “Pray, sir, who are you?” “George Faulkner, the printer, sir.” “You, George the printer! why, you are the most impudent barefaced scoundrel of an impostor I have ever met! George Faulkner is a plain sober citizen, and would never trick himself out in lace and
other fopperies. Get you gone, you rascal, I will immediately send you to the house of correction.” Away went George as fast as he could, and having changed his dress he returned to the deanery, where he was received with the greatest cordiality. “My friend George,” said the Dean, “I am glad to see you returned safe from London. Why, there has been an impudent fellow just with me dressed in lace waistcoat, and he would fain pass himself off for you, but I soon sent him away with a flea in his ear.”
Dress is certainly an index to the mind. It shows the spirit and internal quality of the soul, and “there cannot be a more evident gross manifestation of a poor, degenerate breeding, than a rude, unpolished, disordered and slovenly outside.” The boy that does not polish his shoes, comb his hair, brush his clothes, is in all probability morally affected. To consider such things matters of small importance is a grave mistake, for they often prove to be hinges on which the doors of opportunity swing.
THE BOY’S RECOMMENDATION.
Said a friend to a business man on coming into the office, “I should like to know on what ground you selected that boy, who had not a single recommendation.” “You are mistaken,” said the gentleman, “he had a great many. He wiped his feet when he came in and closed the door after him, showing that he was careful; he gave his seat instantly to that lame old man, showing that he was thoughtful; he took off his cap when he came in, and answered my questions promptly, showing that he was gentlemanly; he waited quietly for his turn, instead of pushing and crowding, showing that he was honorable and orderly. When I talked to him I noticed that his clothes were brushed, his hair in order, and when he wrote his name, I noticed that his finger-nails were clean. Don’t you call those things letters of recommendation? I do, and I would give more for what I can tell about a boy by using my eyes ten minutes than all the letters he can bring me.”
Be neat and clean in appearance, and not less so in habit. At home never throw your hat in one chair and your coat in another. Have a place for everything and put everything in its place. In school or at
work let the same principle govern you, for “what is worth doing is worth doing well.” The boys now wanted are
“Boys of neatness, boys of will, Boys of muscle, brain and power, For to cope with anything These are wanted every hour.”
CHAPTER II
Be Polite
INTRODUCTION TO CHAPTER II
B A S .
Conduct is three-fourths of life. Matthew Arnold.
Character makes the man; character and politeness mark the perfect man. The first is the diamond in the rough; the second the cut stone. The former may attract the attention of a few, the latter discloses hidden beauties and compels the admiration of all.
The “grand old name of gentleman” can only belong to him who unites the qualities of gentleness and manliness, and politeness is essentially gentleness.
The exercise of politeness benefits all, chiefly him who practises it, and this is a sure road to success.
CHAPTER II
B P .
William of Wickham, Bishop of Winchester, and founder of Winchester and of New College, Oxford, was so convinced of the value of manners that he had the phrase “Manners Make a Man,” inscribed in several places upon the walls of those structures. “Good manners,” said Emerson, “are made up of petty sacrifices.” Pleasant expression and action, pleasing exterior and true kindness are gentle delights which win the esteem of others and often contribute to one’s advancement more than real merit. Coarseness and gruffness, loose habits and “don’t-care” manners, never fail to lock doors and close hearts. “You had better,” wrote Chesterfield to his son, “return a dropped fan genteelly, than give a thousand pounds awkwardly; better refuse a favor gracefully than grant it clumsily. All your Greek can never advance you from secretary to envoy, or from envoy to ambassador; but your address, your air, your manners, if good, may.” These will give, as Emerson says, “The mastery of palaces and fortunes wherever one goes without the trouble of earning or owning them.”
Cultivation of politeness is like putting the finishing touch upon the picture, it sets one off to the best advantage. Like a flower bed encircling the lawn, it beautifies character. Like a lamp in a dark room, it makes one’s presence cheerful. Nothing has greater influence, and as Matthew Arnold said, “It is three-fourths of life.” As honey on the skin is a protection from the sting of the bee, so politeness will be a safeguard from the stings of the world. Doors will open at its knock. Sunbeams will sparkle in its presence, and everywhere, with everyone, it will act as a magic passport.
DEFINITION OF POLITENESS.
Politeness has been defined in various ways, but all meet at the same point, like the spokes of a wheel which center in the hub. “It is the art of showing, by external signs, the internal regard we have for others.” “It is,” said Lord Chatham, “benevolence in little things,” as
the giving others the preference in every enjoyment at the table, walking, sitting or standing. “It is a willingness to please and to be pleased.” “It consists in treating others just as you love to be treated yourself.” Henry IV, King of France, was once taken to task for returning the salute of a poor man as he was passing through a village. He replied, “Would you have your king exceeded in politeness by one of his meanest subjects?” Because Nicholas I, Czar of Russia, saw an officer of his household treat an old beggar woman discourteously, he summoned him to his imperial presence. The official was quite pleased. Nicholas soon undeceived him, and in the presence of a dozen courtiers cut him to the quick with his indignant reproof. “Enough!” he said, finally, “you will walk up and down that corridor all night, and every time you turn you will say, in a loud voice, ‘I am a puppy! I am a puppy!’”
“I treat him as well as he treats me,” said a boy to his mother. She had just reproved him because he did not attempt to amuse or entertain a boy friend who had gone home. “I often go in there and he doesn’t notice me,” said the boy. “Do you enjoy that?” asked the mother. “O! I don’t mind, I don’t stay long,” was the reply. “I should call myself a very selfish person,” remarked the mother, “if friends came to see me and I should pay no more attention to them.” “Well, that’s different, you’re grown up,” answered the son. “Indeed!” replied the mother, “then you really think that politeness and courtesy are not needed among boys?” The boy thus pressed, said he didn’t mean exactly that. His father, having overheard the conversation, turned to him and said: “A boy or a man who measures his treatment of others by their treatment of him, has no character of his own. He will never be kind or generous. If he is ever to be a gentleman, he will be so in spite of the boorishness of others. If he is to be noble, no other boy’s meanness will change his nature. Remember this, my son, you lower yourself every time you are guilty of an unworthy action because someone else is. Be true to your best self, and no boy can drag you down, nor will he want to.”
Years ago, when Queen Victoria began her reign, the famous Lord John Russell was the minister in attendance upon her majesty at her Scottish home. There came late one evening a messenger—a little old man buried in a greatcoat—to the Aboyne telegraph office, and delivered to the clerk a message from Lord John Russell to one of the
officials of the government in London. The message did not bear a signature. On seeing this, the ill-mannered clerk flung it back to the old man, and said, “Put your name to it; it’s a pity your master doesn’t know how to send a telegram.” The name was added and the message handed back. “Why, you can’t write either,” cried the enraged clerk, after vainly trying to make out the signature; “here, let me do it for you. What’s your name?” “My name,” said the little old man, very deliberately, “is John Russell.” Through his impoliteness that clerk lost his position.
POLITENESS A BADGE OF TRUE GENTILITY.
In some European countries the word gentleman stands for a titled or wealthy man. When Sir Lawrence Alma-Tadema was knighted a lady expressed herself to his lordship thus: “O, dear Sir Lawrence, I am awfully glad to hear of the honor you have received; I suppose now that you have been knighted you’ll give up painting pictures and live like a gentleman.” Many are they who have this idea of gentlemanship. But in our land the real gentleman stands for such personal qualities as honesty, truthfulness, gentleness and gracefulness which characterize a boy or man. Such a gentleman subjects his appetite, refines his taste, subdues his feelings and controls his speech. When accidentally running against or passing before another, it will be, “I beg your pardon.” “Please excuse me.” When receiving a gift or extending a favor, it will be, “I thank you.”
Some boys are not careful in their expressions. “Sir,” said Doctor Johnson, “A man has no more right to say a rude thing to another than to knock him down.” A young man once accosted Zachariah Fox, a Quaker, a rich merchant of Liverpool, with “Old chap, how do you make all your money?” The Quaker replied, “By dealing in an article that thou may’st deal in if thou wilt—civility.”
Monroe was so polite that he was called “A Gentleman of the Old School.” Henry Clay was said to make the most engaging bow of any gentleman of his day. Madison made it a point to touch his hat to everyone who bowed to him, and the front part of it was always worn threadbare in consequence of his lifting it. William Penn’s formal but kindly politeness impressed even the Indians with whom he dealt, so
that they named him: “The Good-Big Chief.” James Russell Lowell was as courteous to a beggar as to a lord, and was once observed holding a long conversation in Italian with an organ-grinder whom he questioned about scenes in Italy with which both were familiar. “You should not have returned their salute,” said the master of ceremonies, when Clement XIV bowed to the ambassadors who had bowed in congratulating him on his election. “Oh, I beg your pardon,” replied Clement, “I have not been pope long enough to forget good manners.”
A number of years ago a company of workmen was standing before a store in Oxford street, London, looking at some pictures. The Honorable William E. Gladstone, who was then at the height of his popularity, halted a moment to look at the artist’s work. One of the workmen recognized him and stepping up, said, “Excuse me, Mr. Gladstone, but I should like to shake hands with you.” “Why, of course, I shall be glad to do so,” the Premier of England responded, as he extended his hand not only to the man who had accosted him but also to the little group of men who stood near, taking no notice of soiled hands or garments. Then he directed their attention to a fine engraving in the window, quietly pointing out not only its beauty, but some special feature in its execution that constituted its charm. Then raising his hat with a smile he bade the men “Good morning,” and passed on his way up the street. No wonder that in later years his fellow-countrymen called him “The Grand Old Man,” “The People’s William.” He was a gentleman, exhibiting a lovely spirit of true friendship and absolute equality.
POLITENESS SHOULD BE FIRST PRACTISED AT HOME.
What one is in the home is a fair criterion as to what he will be away from home. The manner in which a person conducts himself in the home determines largely his course and conduct in life. He who is polite and kind to his parents, considering their wishes, and heeding their advice and counsel, paves the way to future happiness and success. But he who spurns paternal suggestions, speaks and acts disrespectfully, is seldom respected and is always at a disadvantage. When Prince Bismarck was a boy, he was rebuked by his father for speaking of the King as Fritz. “Learn to speak
reverently of his Majesty,” said the old squire of Varzin, “and you will grow accustomed to think of him with veneration.” Bismarck laid the advice to heart and from that day profited by it.
The truly polite boy is not only respectful to his parents but also to his sisters and brothers, always returning a pleasant “Thank you” for any kindness received at their hands, and showing as much courtesy to all at home as to those in the home of a neighbor. “A beautiful form,” says an American essayist, “is better than a beautiful face, and a beautiful behavior is better than a beautiful form; it gives a higher pleasure than statues or pictures; it is the finest of the fine arts,” it gives grace to one’s bearing and enables one to look on the bright and beautiful side of things.
POLITENESS SHOULD BE ACCORDED ALL.
Politeness is a universal debt that each boy owes to every person. The matter of caste, sex, position and intelligence have nothing whatever to do with it. It should be the rule of conduct wherever and in whatever society one may be, to practise politeness.
Charles V was renowned for his courtesy. When he passed John Frederick, Elector of Saxony, he took off his hat and bowed to him, though his prisoner, who had been taken by him in battle. The poet Burns was one day walking in the street of Edinburgh when an honest farmer saluted him, which salute he returned, when some one rebuked him. Mr. Burns replied that it was not the greatcoat, the scone bonnet or the saunders boot-hose that he spoke to, but the man that was in them. Daniel Webster was once walking with a friend in Washington when a colored man passing by bowed very low to him. Mr. Webster promptly returned as deep an obeisance. “Do you bow in that way to a darky?” asked his friend. “Would you have me outdone in politeness by a negro?” replied the great statesman.
WHAT POLITENESS DID.
Mr. Winans, of Philadelphia, became independently rich through his courteous manner. One day two strangers called on him. One was
a foreigner who had visited some larger establishments in the city, but on their coming to Mr. Winans’, a third or fourth rate factory, he took so much pains to show all its parts and workings, and was so patient in his explanations and answers to their inquiries, that within a year he was surprised by an invitation to transfer his labors to St. Petersburg and manufacture locomotives for the Czar of Russia, He went, accumulated a large fortune, and ultimately received from his Russian workshops a hundred thousand dollars a year. Investing his money in real estate he laid the foundation of one of the largest private fortunes in Philadelphia; and all this was the result of civility. It pays to cultivate politeness. To this day the Japanese people revere the memory of General Grant. While visiting the emperor, he was invited to cross the imperial foot bridge near the palace at Tokyo, across which none but the blood royal had ever trod. General Grant accepted the invitation and walked beside the Mikado until they reached the center of the bridge. Then he stopped, profoundly saluted the emperor, and said: “Your majesty, I have come so far to show you that I was not insensible to the honor you would do me, but I cannot violate your traditions. Let us return the way we came.”
Politeness serves one well. It is keener than sharpened steel. It is more magnetic than loadstone and worth more than jewels. At home or abroad, among young and aged, employers or teachers, inferiors or superiors, this glorious characteristic is a diadem from which sparkles a jewel, which is, as Chesterfield said: “The treatment of others just as you love to be treated yourself.” In the words of One greater than he, it is, “Do unto others as ye would they should do unto you.” All other things being equal, the boy who adheres to these mottoes is the one who succeeds. It makes him an acceptable companion, wins friendship and creates popularity. “Give a poor boy fine manners and accomplishments,” said Voltaire, “and he will become the master of fortunes and palaces, while princes stand upon their threshold to solicit his friendship.” Charles II. is described by Macaulay as being “the grandest rascal and most popular man in England.” Hume in giving the reason of this says, “He was the best bred man alive.” “What thou wilt, Thou must rather enforce it with thy smile, Than hew to it with thy sword.”
CHAPTER III
Be Truthful
INTRODUCTION TO CHAPTER III
B J L
Once to every man and nation comes the moment to decide, In the strife of Truth with Falsehood, for the good or evil side. Lowell.
It is related of Cyrus, that when asked what was the first thing he learned, he replied, “To tell the truth.” Truthfulness is the foundation stone of character. Without it, a life, as it is developed, becomes more and more marred and falls short of its highest opportunity and calling. All qualifications that go to make up noble manhood count for naught, where there is not a persistent adherence to truthfulness. Therefore be true to yourself and the nobler impulses and yearnings of your heart by always speaking the truth, acting the truth, and living the truth.
CHAPTER III
B T
While a vessel was crossing the English Channel, a gentleman stood near the helmsman. It was a calm pleasant evening, and no one expected a storm. The flapping of a sail as if the wind had suddenly shifted, caught the ear of the officer on watch, and springing to the wheel, he examined the compass. “You are half a point off the course,” he sharply said to the man at the wheel. The deviation was corrected, and the officer returned to his post. “It must be necessary to steer very accurately,” said the observer, “if half a point is of so much importance.” “Ah!” remarked the officer, “a half a point, sir, is liable to bring us directly on the rocks.” What a lesson for every boy. The half a point deviation from strict truthfulness strands one on the rocks of falsehood.
WHAT IS A LIE?
The shortest definition of a lie is, “The intention to deceive.” It may not be telling an out-and-out falsehood to conceal a crime, or to shield one’s self, but telling it to mislead or deceive others. “The essence of the thing,” said Dewey, “lies in the intention,” and if the intention is to mislead, such, as Immanuel Kant says, “is forfeiture of personal worth, a destruction of personal integrity.” As he contends, “a lie is the abandonment, or, as it were, the annihilation of the dignity of man.” It will undermine the noble instincts of any boy and cause his character to collapse.
TELL THE TRUTH.
A story of Abraham Lincoln shows his love for truth. It was a bright autumn evening, when Abraham, a great awkward boy of sixteen or seventeen said to his mother, “I’m going to the woods tomorrow. I’ve got a good job at Laird’s and as I shall be obliged to start by day-break, I thought there might be some chores you wished
to have done.” “You are a good boy, Abram, always thinking of helping me,” said his step-mother. “If I was your own mother you could not be more kind, and God will reward you sometime. Tomorrow, I am going to wash, and I would be very thankful if you would bring me a few buckets of water from the spring.” Back and forth the tall boy hurried, until all the tubs and kettles about the cabin were filled. Early next morning, when Abraham was ready to start for the place where the rails were to be split, his little sister Sally said, “Can’t I go, Abram?” “Just as mother says,” replied he, pausing to give the little girl an opportunity to consult her mother. The mother would not consent. No sooner had Abram started than she determined to follow him, and at once cut across the field intending to reach the ravine before him and give him a genuine surprise by jumping out unannounced in the path as he came up. She carried out her plan successfully, and when she heard his merry whistle in the distance she climbed upon the bank to be ready to make the spring for his shoulders when the proper moment arrived. But the poor child had forgotten all about the sharp axe which he carried, and although she gained her coveted seat on his broad shoulders, her little bare foot received a gash from the cruel axe, which changed her merry laugh into a bitter cry. “Why, Sally! How did you get here?” was all the boy could say as he placed her tenderly on the bank and began an examination of the wounded foot. Finding it to be a deep cut, he gathered some broad plantain leaves which grew near, and by their aid soon succeeded in staunching the flow of blood. This accomplished, he tore the sleeve from his shirt, and in his clumsy way bandaged the injured foot. Carrying her home, he learnt the story of her disobedience. She would have been willing to evade the truth in order to screen herself from her mother’s displeasure, but honest, truthful Abraham would not permit this. “Tell the truth, Sally, no matter what the consequences may be,” he insisted; “better suffer punishment than lie about it. I don’t think mother will be hard on you when she sees how sorely punished you are; but never tell a lie to shield yourself, never.” Such was the course taken through life by that boy who later became the honored President of these United States.
WHITE AND BLACK LIES.
Much is said nowadays about degrees in lying. That is lying in a small way. There is the so-called white lie of custom when a certain article is slightly misrepresented to make a bargain; the white lie of courtesy when one makes politeness the garb behind which he deceives; the white lie of necessity, when one would evade the truth by nodding the head, or giving a wrong impression. Some men, and even great men, have maintained that this is sometimes a necessity, but would it not be a fine moral precept to say, “You must speak the truth generally, but you may utter a falsehood when it suits your convenience?” Who ever licensed one thus? Justin Martyr said, “Is life at stake? We would not live by telling a lie.” When Atillius Regulus was a prisoner of the Carthaginians he was sent by that great people to Rome with several ambassadors to arrange for peace, on the understanding that if peace-terms were not agreed upon he was to return to prison. He took the oath and swore to return. Arriving at Rome he urged his countrymen to continue in war and not agree to the exchange of prisoners. This meant to him the return to Carthage. The senators and priests held that as his oath had been forced from him he ought not to return. Then came the answer from Regulus which has made him imperishable: “Have you resolved to dishonor me? I am not ignorant that death and tortures are preparing for me. But what are those to the shame of infamous action, or the wounds of a guilty mind? Slave as I am to Carthage, I have still the spirit of a Roman. I have sworn to return. It is my duty to return. Let the gods take care of the rest.”
“One should never lie,” said Crispi, the great Italian statesman. “I will not stain speech with a lie,” said Pindar. “The genuine lie is hated by all gods and men,” said Plato. “That man has no fair glory,” said Theognis, “in whose heart dwells a lie, and from whose mouth it has once issued.” A lie is never justifiable, and to lie a little, is, as Victor Hugo remarked, “not possible.” The person who lies tells the whole lie, lying in the face of the fiend, and “Satan has two names, Satan and lying.” Therefore
“Let falsehood be a stranger to thy lips; Shame on the policy that first began To tamper with the heart to hide its thoughts! And doubly shame on that inglorious tongue That sold its honesty and told a lie.”
WHAT LYING DOES.
Nothing so corrupts early simplicity, quickly destroys the nobler instincts, and depraves the heart as falsehood. If a boy will lie about one thing, can he be trusted in anything? If he is branded as a liar, what teacher will respect him, what business man will engage him, and what court will accept his testimony? “I have seldom known anyone,” said Paley, “who deserted truth in trifles, who could be trusted in matters of importance.” Oliver Wendell Holmes said: “Sin has many tools, but a lie is the handle which fits them all.” It destroys confidence, establishes false relations among men, blights the bloom of life, and saps the vital springs of existence. It is the progenitor of all wrongs, oppressions, cruelties and crimes, and what boy is there who dare do it when God prohibits it?
WHAT LYING BRINGS.
Like begets like, thus lies beget lies. Said Owen, “One lie must be thatched over with another, or it will soon rain through.” Lying brings misery. It troubles the conscience, destroys the peace of mind and makes one suspicious of others. Because of this, Eugene Field, when a young man, walked thirty miles to confess to his employer and to ask forgiveness for an untruth he had told him. Lying brings punishment, for “lying lips are an abomination unto the Lord.” Because of this Elisha’s servant was struck with leprosy, Ananias and Sapphira with death, and many others have had the seal of God’s wrath placed upon them.
One day, as Archbishop Leighton was going from Glasgow to Dumblane, a storm of lightning and thunder burst upon him. He was observed, when at a considerable distance, by two men of bad character. They had not the courage to rob him; but, wishing to extort money from him, one said, “I will lie down by the wayside as if I were dead, and you shall inform the archbishop that I was killed by the lightning and beg money of him to bury me.” When the Archbishop arrived, the wicked wretch told the fabricated story. The Archbishop sympathized with the pretended survivor, gave him money, and proceeded on his journey. But when the man returned to
his companion, he found him really lifeless. Immediately he began to cry aloud: “Oh, Sir! he’s dead! Oh, Sir, he’s dead!” On this the Archbishop discovered the fraud and turning to the living man said, “It is a dangerous thing to trifle with the judgment of God.” How much better and safer to speak the truth, for
“There is nothing so kingly as kindness, And nothing so royal as truth.”
Truthfulness is the foundation of character. It is the basis of true manhood. Its spirit pervades the closest relation and highest intercourse, its law holds the planets in their course, and it is the presiding principle of every true and noble life. A greater tribute could not be paid to anyone than “his word is as good as his bond.” No more worthy epitaph or eloquent remark could be uttered of Colonel Huchurin, than when a friend, attesting the simplicity and nobility of him, said: “He never professed the thing he intended not.” No eulogy can surpass Xenocrates of Petrarch, who, standing before an ecclesiastical tribunal where an oath had been required of others, said, “As for you, Petrarch, your word is sufficient.”
An important conference was being held in the Executive Mansion in Washington. A caller had sent in his card, but either the caller was unwelcome or the time was quite unsuitable for his admission. One of the persons turned to a servant and said, “Tell the person who sent up the card that the President is not in.” “No,” said General Grant, “tell him no such thing.” Then, turning to his friends, he remarked: “I don’t lie myself, and I don’t want any of my servants to lie for me.”
A “Mental Photograph” book was once presented to Charles Kingsley in which to write. One question was “What is your bête noire?” “A lie,” he penned. In dedicating her delightful biography of him his wife wrote:
“To the beloved memory of A righteous man
Who loved God and truth above all things. A man of untarnished honor
Loyal and chivalrous gentle and strong
Modest and humble tender and true
Pitiful to the weak yearning after the erring
Stern to all forms of wrong and oppression, Yet most stern toward himself Who being angry yet sinned not.”
TRUTHFULNESS IS THE MOST HONORABLE AND SAFE COURSE.
Truthfulness underlies all honest and faithful work, all social confidence, all right fulfillment of relations and self-respect. It regulates lives and improves and elevates those it characterizes. It is one great secret of success in business, a magnet that draws confidence and wields a power second to none in the universe. A poor Persian boy was about to leave his mother’s home, to engage in business in the city. Within the lining of his coat she sewed forty golden dinars which she had saved during years of labor. Before the boy started she cautioned him to beware of robbers as he went across the desert, and as he left the home, she said: “Fear God, and never tell a lie.” The boy started, and toward evening saw in the distance the glittering minarets of the great city, but between the city and himself he saw a cloud of dust. It came nearer. Presently he saw that it was caused by a band of robbers. One of them approached him, and unceremoniously inquired what valuables he had. The boy answered with candor: “Forty golden dinars are sewed up in my garments.” Discrediting the boy’s story he wheeled his horse around and rode back to his companions. Soon another robber came and said: “Boy, what have you got?” “Forty dinars sewed in my garments,” he answered. The robber laughed and rode away. At last the chief came and asked him what he had. The boy replied, “I have already told two of your men that I have forty dinars sewed up in my clothes.” The chief ordered his clothes torn open, and the money was found. He was then asked what induced him to make such a revelation. “Because,” said the boy, “I would not be false to my mother, whom I solemnly promised never to tell a lie.” The robber leaned upon his spear and after reflecting said, “Wait a moment.” He mounted his horse and rode back to his comrades, but soon returned dressed as a merchant. “Boy,” said he, “art thou so mindful of thy mother, while I am insensible at my age of that duty I owe God? Give me thy hand, that I may swear repentance on it.” He did so, and his
followers were struck with the scene. Said he, “I am a merchant. I have a large business house in the city. I want you to come and live with me to teach me about your God, and you will be rich, and your mother some day shall come and live with us.” Then one of the robbers turned to the chief and said, “You have been our leader in guilt, be the same in the path of virtue.” And taking the boy’s hand, they all promised to lead new lives.
Boys, speak only that which is true. You may do much good by it, although you may never lead a band of robbers to God and honesty. But—
“Nothing good shall ever perish, Only the corrupt shall die; Truth, which men and angels cherish, Flourishes eternally.”
TRUTHFULNESS IS THE WINNING SIDE.
Good old Matthew Henry used to say, “Truth is mighty and will prevail.” “Falsehood,” as one of the kings of Prussia said, “sometimes does good for twenty-four hours, but like a battle well fought, right comes off more than conqueror.” Falsehood is always defeated. It shrinks at detection and in due time is compelled to confess. Truth is sure and has a firm foundation because it is an attribute of God. And “God and truth,” said Theodore Parker, “are always on the same side.” Therefore
“Seize upon truth, where’er ’tis found, Amongst your friends, amongst your foes, On Christian or on heathen ground; The flower’s divine where’er it grows. ”
