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16 views45 pages

(Ebook PDF) Introduction To Bioinformatics 5th Edition Instant Download

The document provides information about various eBooks related to bioinformatics and other scientific topics available for download. It includes links to titles such as 'Introduction to Bioinformatics 5th Edition' and 'Encyclopedia of Bioinformatics and Computational Biology.' Additionally, it outlines the contents of the 'Introduction to Bioinformatics' book, covering topics from genetics to systems biology.

Uploaded by

kpkyaxevp9810
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© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

CONTENTS

Preface to the fifth edition xv


Plan of the book xxi
Introduction to bioinformatics on the web xxii
Acknowledgements xxiii

1 Introduction 1
Life in space and time 4
Phenotype = genotype + environment + life history + epigenetics 4
Evolution is the change over time in the world of living things 5
Biological classification and nomenclature 6
Dogmas: central and peripheral 9
The structure of DNA 9
Transcription and translation 12
The structures of proteins 12
Statics and dynamics 17
Systems biology 17
The human genome 19
Variation in human genome sequences 20
The human genome and medicine 21
Databases in molecular biology 28
Observables and data archives 29
A database without effective modes of access is merely a data graveyard 29
Information flow in bioinformatics 31
Curation, annotation, and quality control 32
The World Wide Web 33
Electronic publication 34
Computers and computer science 34
Programming 35
Après moi, le déluge? Sorry—too late! 38
How much sequencing power is there in the world? 41
How does the amount of data in bioinformatics compare with other large scientific
information archives? 41
Recommended reading 42
Exercises and Problems 43

2 From genetics to genomes 48


The classical genetics background 49
DNA embodies genes 50
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viii Contents

Maps and tour guides 51


Linkage maps 51
Linkage 51
Chromosome banding 53
High-resolution maps, based directly on DNA sequences 55
Restriction maps 56
DNA sequencing 57
Frederick Sanger and the development of DNA sequencing 57
DNA sequencing by termination of chain replication 58
Automation of DNA sequencing 60
Next-generation sequencing 61
Paired-end reads 66
Life in the fast lane 67
Assembly—computational aspects 68
Pattern matching 68
Suffix trees 68
Fragment assembly 70
Genomics in personal identification 73
DNA ‘fingerprinting’ 74
Personal identification by amplification of specific regions has superseded
the RFLP approach 75
Mitochondrial DNA 76
Analysis of non-human DNA sequences 77
Parentage testing 78
Ethical, legal, and social issues 80
Databases containing human DNA sequence information 80
Use of DNA sequencing in research on human subjects 82
Recommended reading 83
Exercises and Problems 84

3 The panorama of life 88


Genomes, transcriptomes, and proteomes 89
Genes 89
Proteomics and transcriptomics 91
Eavesdropping on the transmission of genetic information 93
Genome-sequencing projects 93
Genomes of prokaryotes 94
The genome of the bacterium Escherichia coli 95
The genome of the archaeon Methanocaldococcus jannaschii 97
The genome of one of the simplest organisms: Mycoplasma genitalium 98
Metagenomics: the collection of genomes in a coherent environmental sample 99
The human microbiome 101
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Contents ix

Genomes of eukarya 102


Gene families 103
The genome of Saccharomyces cerevisiae (Baker’s yeast) 103
The genome of Caenorhabditis elegans 105
The genome of Drosophila melanogaster 105
The genome of Arabidopsis thaliana 107
The genome of Homo sapiens (the human genome) 108
Protein-coding genes 109
Repeat sequences 109
RNA 110
Single-nucleotide polymorphisms and haplotypes 110
Systematic measurements and collections of single-nucleotide
polymorphisms 113
Genetic diversity in anthropology 114
DNA sequences and languages 116
Evolution of genomes 116
Please pass the genes: horizontal gene transfer 118
Comparative genomics of eukarya 119
Recommended reading 120
Exercises and Problems 121

4 Alignments and phylogenetic trees 123


Introduction to sequence alignment 124
Dotplots and sequence alignments 130
Measures of sequence similarity 132
Scoring schemes 132
Derivation of substitution matrices: PAM matrices 133
Computing the alignment of two sequences 135
Variations and generalizations 135
Approximate methods for quick screening of databases 135
The dynamic programming algorithm for optimal pairwise sequence
alignment 137
Significance of alignments 141
Multiple sequence alignment 143
Applications of multiple sequence alignments to database searching 143
Profiles 146
PSI-BLAST 147
Complete pairwise sequence alignment of human PAX-6 protein and Drosophila
melanogaster eyeless 151
Hidden Markov Models 152
Phylogeny 154
Determination of taxonomic relationships from molecular properties 155
Use of sequences to determine phylogenetic relationships 159
Use of SINES and LINES to derive phylogenetic relationships 161
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x Contents

Phylogenetic trees 162


Clustering methods 164
The maximum-likelihood method 165
Reconstruction of ancestral sequences 165
Pyruvate decarboxylase: synthesis, activity, and crystal structure of predicted ancestor 167
The problem of varying rates of evolution 168
Bayesian methods 169
Are trees the correct way to present phylogenetic relationships? 169
Computational considerations 170
Putting it all together 171
Recommended reading 171
Exercises and Problems 172

5 Structural bioinformatics and drug discovery 177


Introduction 178
Protein stability and folding 180
The Sasisekharan–Ramakrishnan–Ramachandran plot
describes allowed mainchain conformations 180
The sidechains 181
Protein stability and denaturation 183
Protein folding as a process 185
Applications of hydrophobicity 187
Coiled-coiled proteins 187
Description of the variety of protein structures 190
Superposition of structures, and structural alignments 192
Evolution of protein structures 197
Classifications of protein structures 199
SCOP 199
Protein structure prediction and modelling 201
A priori and empirical methods 202
Critical Assessment of Structure Prediction 203
Secondary structure prediction 204
Homology modelling 205
Fold recognition 205
Conformational energy calculations and molecular dynamics 207
ROSETTA 209
Protein structure prediction from contact maps derived from correlated mutations
in multiple sequence alignments 210
Design of novel proteins 213
Drug discovery and development 215
The lead compound 216
Improving on the lead compound: quantitative structure–activity relationships 217
Bioinformatics in drug discovery and development 218
Molecular modelling in drug discovery 219
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

Contents xi

Recommended reading 225


Exercises and Problems 228

6 Scientific publications and archives: media, content, access,


and presentation 233
The scientific literature 234
Access to scholarly publications 235
Open access 236
The Public Library of Science 237
Traditional and digital libraries 237
How to populate a digital library 238
The information explosion 239
The web: higher dimensions 239
New media: video, sound 240
Searching the scientific literature 240
Bibliography management 241
Databases 242
Database contents 242
Database quality control 243
The literature as a database 244
Database organization 244
Annotation 246
Markup languages 248
Database access 250
Links 250
Database interoperability 251
Data mining 251
Programming languages and tools for database construction and access 255
Traditional programming languages 255
Scripting languages 256
Program libraries specialized for molecular biology 256
Java—computing over the web 256
Natural language processing 257
Natural language processing in mining the biomedical literature 258
Biomedical applications of text mining 260
Hypothesis generation 264
A glaucoma-related network derived by text mining 265
Recommended reading 268
Exercises and Problems 269

7 Artificial intelligence and machine learning 271


What are artificial intelligence and machine learning? 272
Classification and clustering 273
Binary classifier 276
Receiver Operating Characteristic (ROC) curves 277
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xii Contents

Artificial neural networks 279


Self-organizing maps 281
Decision trees 281
Support vector machines (SVMs) 286
Kernel methods 286
Clustering 287
Clustering by graph spectral theory 291
Recommended reading 293
Exercises and Problems 293

8 Introduction to systems biology 296


Introduction 297
Networks and graphs 298
Connectivity in networks 299
Dynamics, stability, and robustness 301
Some sources of ideas for systems biology 302
Complexity of sequences 302
Shannon’s definition of entropy 303
Complexity of sequences 304
The relationship between complexity, randomness, and compressibility 305
The Burrows-Wheeler Transform 305
Inverting the Burrows-Wheeler Transform 306
The Burrows-Wheeler Transform brings repeats together, facilitating compression 306
Use of the Burrows-Wheeler transform for searching for patterns in strings 306
Complexity of other types of biological data 308
Static and dynamic complexity 308
Predictability and chaos 309
Analysis and comparison of networks 310
Analysis of graphs by matrix algebra 311
Graph isomorphism 312
Recommended reading 314
Exercises and Problems 314

9 Metabolic pathways 317


Introduction 318
Classification of protein function 320
The Enzyme Commission 320
The Gene OntologyTM Consortium protein function classification 320
Prediction of protein function 321
Catalysis by enzymes 324
Active sites 325
Cofactors 325
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Contents xiii

Protein–ligand binding equilibria 326


Enzyme kinetics 327
Measures of effectiveness of enzymes 328
How do enzymes evolve new functions? 329
Control over enzyme activity 329
Structural mechanisms of evolution of altered or novel protein functions 329
Pathways and limits in the divergence of sequence, structure,
and function 334
Evolution by gene duplication 335
Databases of metabolic pathways 337
The Kyoto Encyclopedia of Genes and Genomes (KEGG) 339
Evolution and phylogeny of metabolic pathways 341
Pathway comparison 341
Alignment of metabolic pathways 343
Comparing linear metabolic pathways 343
Comparing non-linear metabolic pathways: The pentose phosphate pathway
and the Calvin-Benson cycle 346
Dynamics of metabolic networks 347
Robustness of metabolic networks 347
Dynamic modelling of metabolism 347
Simulation of metabolic pathways in Plasmodium falciparum 351
The Human Metabolome Database supports clinical applications to the study
of inborn errors of metabolism, and to cancer 352
Recommended reading 353
Exercises and Problems 353

10 Control of organization and organization of control 355


Transcriptomics 356
The ENCODE Project 357
Determination of RNA sequences 358
RNAseq v. microarrays 358
DNA microarrays 359
RNAseq 363
The Genotype-Tissue Expression (GTEx) project 366
Expression patterns in different physiological states 367
Variation of expression patterns during the life cycle of Drosophila
melanogaster 368
Different life stages make different demands on different genes 370
Protein complexes and aggregates 373
Properties of protein–protein complexes 373
Protein interaction networks 375
Components of the primosome assembly in Bacillus subtilis 378
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

xiv Contents

Regulatory networks 380


Signal transduction and transcriptional control 380
Structural biology of regulatory networks 382
Examples of relatively simple regulatory control networks 383
Regulation of the lactose operon in E. coli 383
The genetic switch of bacteriophage λ 385
The diauxic shift in Saccharomyces cerevisiae 389
Logical structure of regulatory networks 391
The transcriptional regulatory network of E. coli 391
The transcriptional regulatory network of Saccharomyces cerevisiae 392
Adaptability of the yeast regulatory network 393
Recommended reading 396
Exercises and Problems 396

Conclusions 399
Index 400
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

PREFACE TO THE FIFTH EDITION

On June 26, 2000, the sciences of biology and to prevent Celera—or anyone else—from applying
medicine changed forever. Prime Minister of the for patents.
United Kingdom Tony Blair and President of The academic groups lined up against Celera were
the United States Bill Clinton held a joint press a collaborating group of laboratories based primar-
conference, linked via satellite, to announce the ily but not exclusively in the UK and USA. These
completion of the draft of the Human Genome. The included the Wellcome Trust Sanger Institute in Eng-
New York Times ran a banner headline: ‘Genetic land; Washington University in St. Louis, Missouri;
Code of Human Life is Cracked by Scientists’. The the Whitehead Institute at the Massachusetts Institute
sequence of 3 billion bases was the culmination of of Technology in Cambridge, Massachusetts; Baylor
over a decade of work, during which the goal was College of Medicine in Houston, Texas; the Joint
always clearly in sight and the only questions were Genome Institute at Lawrence Livermore National
how fast the technology could progress and how Laboratory in Livermore, California; and the RIKEN
generously the funding would flow. The Table shows Genomic Sciences Center, now in Yokahama, Japan.
some of the landmarks along the way. Both sides could dip into deep pockets. Celera had
Next to the politicians stood the scientists. The its original venture capitalists; its current parent com-
late John Sulston (later Sir John, CH, FRS), Direc- pany, the PE Corporation; and, after going public,
tor of the Wellcome Trust Sanger Institute in the anyone who cared to take a flutter. The UK Medical
UK, had been a key player since the beginning of Research Council and The Wellcome Trust supported
high-throughput sequencing methods. He had grown the Sanger Institute. The US National Institutes of
with the project from the earliest ‘one man and a Health and Department of Energy supported the US
dog’ stages to the large international consortium. academic labs.
In the US, appearing with President Clinton were On June 26, 2000 the contestants agreed to declare
Francis Collins, director of the US National Human the race a tie, or at least a carefully out-of-focus
Genome Research Institute, representing the US pub- photo finish.
licly funded efforts; and J. Craig Venter, President The sequencing of the human genome ranks
and Chief Scientific Officer of Celera Genomics Cor- with the Manhattan project that produced atomic
poration, representing the commercial sector. It is weapons during the Second World War, and the
difficult to introduce these two without thinking, ‘In space program that sent people to the moon, as one
this corner . . . and in this corner . . . ’. Although never of the great bursts of technological achievement of
actually coming to blows, there was certainly intense the last century. These projects share a grounding in
competition, in the later stages a race. fundamental science, and large-scale and expensive
The race was more than an effort to finish first and engineering development and support. For biology,
to receive scientific credit for priority. It was a race neither the attitudes nor the budgets will ever be
after which the contestants would be tested not for the same. Soon a ‘one man and a dog project’ will
whether they had taken drugs, but whether they and refer only to an afternoon’s undergraduate practical
others could discover them. Clinical applications experiment in sequencing and comparison of two
were a prime motive for support of the Human mammalian genomes.
Genome Project. Once the courts had held that The human genome is only one of the many
gene sequences were patentable—with enormous complete genome sequences known. Taken together,
potential payoffs for drugs and diagnostic tools based genome sequences from organisms distributed widely
on them—the commercial sector rushed to submit among the branches of the tree of life give us a
patents on sets of sequences that they determined, sense, only hinted at before, of the very great unity
and the academic groups rushed to place each bit of in detail of all life on Earth. These results have
sequence that they determined into the public domain changed our perceptions, much as the first pictures
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

xvi Preface to the fifth edition

Landmarks in the Human Genome Project


1953 Watson–Crick structure of DNA published.
1975 F. Sanger, and independently A. Maxam and W. Gilbert, develop methods for sequencing DNA.
1977 Bacteriophage ϕX-174 sequenced: first ‘complete genome’.
1980 US Supreme Court holds that genetically modified bacteria are patentable. This decision was the basis for
patenting of genes.
1981 Human mitochondrial DNA sequenced: 16 568 base pairs.
1984 Epstein–Barr virus genome sequenced: 172 281 base pairs
1990 International Human Genome Project launched: target horizon 15 years.
1991 J. Craig Venter and colleagues identify active genes via expressed sequence tags, sequences of initial
portions of DNA complementary to messenger RNA.
1992 Complete low-resolution linkage map of the human genome.
1992 Beginning of the Caenorhabditis elegans sequencing project.
1992 Wellcome Trust and UK Medical Research Council establish the Sanger Centre for large-scale genomic
sequencing, directed by J. Sulston.
1992 J. Craig Venter forms The Institute for Genome Research (TIGR), associated with plans to exploit sequencing
commercially through gene identification and drug discovery.
1995 First complete sequence of a bacterial genome, Haemophilus influenzae, by TIGR.
1996 High-resolution map of human genome: markers spaced by ∼600 000 base pairs.
1996 Completion of yeast genome, first eukaryotic genome sequence.
May 1998 Celera claims to be able to finish human genome by 2001. Wellcome responds by increasing funding to
Sanger Centre.
1998 Caenorhabditis elegans sequence published.
September 1, 1999 Drosophila melanogaster genome sequence announced, by Celera Genomics; released Spring 2000.
1999 Human Genome Project states goal: working draft of human genome by 2001 (90% of genes sequenced to
>95% accuracy).
December 1, 1999 Sequence of first complete human chromosome published.
June 26, 2000 Joint announcement of complete draft sequence of human genome.
2003 Fiftieth anniversary of discovery of the structure of DNA. Announcement of completion of human genome
sequence.

of Earth from space engendered a unified view of Computing is an essential component of the first
our planet. three of these; CRISPR is spawning bioinformatics
support.
Molecular biology has seen four major break- Where will this lead? We can study the present as
throughs since the previous edition of this book thoroughly as we wish, and the past as extensively as
appeared: we can. What of the future? Molecular biologists used
to be like astronomers, in that we could observe our
• Explosive growth in next-generation genome
subjects but not affect them. This is no longer true:
sequencing
we now have the ability, and the challenge, of direct
• Consistent successful prediction of protein struc- control over living things, including but not limited
ture from amino acid sequence to ourselves.
• Achievement of atomic resolution in cryo-electron A gratifying consequence of this progress is its con-
microscopy tributions to medicine, agriculture, and technology.
• CRISPR for genome editing. A better understanding of life processes empowers us
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

Preface to the fifth edition xvii

to deal with them when they go wrong, and even to lengthier answers or in some cases calculations. The
improve them when they do not. third category, ‘weblems,’ require access to the World
The human genome is fundamentally about Wide Web. Weblems are designed to give readers
information, and computers were essential both practice with the tools required for further study and
for the determination of the sequence and for the research in the field.
applications to biology and medicine that are flowing Examples and problems appear in the text.
from it. Computing contributed not only the raw Weblems are on the Online Resource Centre, a
capacity for processing and storage of data, but also website companion to the book.
the mathematically sophisticated methods required Some computing, based on the widely available
to achieve the results. The marriage of biology and language PERL, is introduced in this book. PERL
computer science has created a new field called is a relatively simple but extremely effective
bioinformatics. programming language. It is one of the languages
Today bioinformatics is an applied science. popular in the bioinformatics community. Similar
Computers have been an essential component of
the projects that determine sequence, structure, and
other types of data. We use computer programs to PERL, PYTHON, and RUBY
make inferences from the data archives of molecular
biology and medicine, to make connections among
As languages, PERL, PYTHON, and RUBY have roughly
them, and to derive useful and interesting predictions.
equivalent ranges of expression. However, applica-
This book is aimed at students and practising
tions of bioinformatics have begun to coalesce around
scientists who need to know how to access the
PYTHON: PYTHON arguably has a richer literature,
data archives, including but not limited to those of
both in training material and in available program mod-
genomes and proteins, how to use the tools that
ules (see, for example, http://rosalind.info/problems/
have been developed to work with these archives, locations/).
and the kinds of questions that these data and tools Nevertheless sample programs in the text are in PERL.
can answer. In fact, there are a lot of sources of this There are two reasons for this. The main one is that PERL
information. Sites treating topics in bioinformatics programs are more self-contained. PYTHON programs
sprawl out all over the Web. Our challenge is to select tend to invoke external ‘black boxes’ and are therefore
an essential core of this material and to describe it, less perspicuous. It is also true that PYTHON is divided
together with the necessary biological background, between PYTHON 2 and PYTHON 3—which to choose?
clearly and coherently, at an introductory level. Unfortunately they are not fully compatible. It is likely
It is assumed that the reader already has some that PYTHON 3 will eventually take over, but a large
knowledge of modern molecular biology, and some amount of legacy software exerts a viscous drag. Also,
facility at using a computer. The purpose of this book presenting PERL programs in the book has the advantage
is to build on and develop this background. It is that readers can be asked to provide PYTHON or RUBY
suitable as a textbook for advanced undergraduates versions as exercises!1
or beginning postgraduate students. Many worked- PERL, PYTHON, and RUBY each has an extensive
out examples are integrated into the text, and refer- repertoire of available components utilizable as ‘stand-
ences to useful websites and recommended reading alone’ modules, or for combination into novel programs:
are provided. A useful list of biomedical courses on- https://bioperl.org, https://biopython.org and https://
line appears at https://www.science.co.il/biomedical/ bioruby.org, and ‘Cookbooks’: Christiansen, T. & Tork-
ington, N. (2009). Perl cookbook 2nd edn; Beazley, D.
Courses.php.
& Jones, B.K. (2013). Python cookbook 3rd edn; and
Problems test and consolidate understanding, pro-
Carlson, L. & Richardson, L. (2015). Ruby cookbook 2nd
vide opportunities to practise skills, and explore addi-
edn; all published by O’Reilly Media, Sebastopol, CA.
tional topics. Three types of problems supplement the
texts of the chapters. Exercises are short and straight- 1 For a comment about PERL to PYTHON conversion see

forward applications. Problems also require no http://code.activestate.com/lists/python-list/292576/


information not contained in the text, but require
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

xviii Preface to the fifth edition

languages include PYTHON and RUBY (see Box on The most striking change in attitude has been
previous page); each of these has its adherents. a refocus on integration; that is, of trying to see
Examples of simple programs appear in the context life processes as unified systems. As I wrote at the
of biological problems. Many simple programming end of Introduction to Protein Science: Architecture,
tasks are assigned as exercises, problems, or weblems Function and Genomics, ‘During the last century,
at the ends of the chapters. molecular biologists have been taking living things
Bioinformatics has grown, explosively, since the apart. Our task now is to understand how to put
first edition of this book appeared. Underlying this them back together.’ We have large amounts of data.
surge are the multiplication and growth of data Now we want to see how they interrelate. At the heart
streams. In addition to genomics, these include, but of life processes are complicated patterns of interac-
are not limited to, transcriptomics, metabolomics, tion among the components, in space and in time.
and regulatory networks. The human genome, To understand these patterns, the field has moved
available in draft form when the first edition towards combining information into networks, and
appeared, is now complete. Large-scale human analysing their structures and dynamics. Many tools
genome sequencing projects are underway. Joining are now available for storing, visualizing, analysing,
these results are the complete genomes of hundreds and comparing networks. Contemporary bioinfor-
of other eukaryote species, very large numbers of matics could not do without them.
prokaryotes, and many other organelle and viral Research and applications require that the data be
sequences. The extension to metagenomics—the available in useful form. It is not enough to make the
survey of distributions of sequences in a region of data public. The information must be subjected to
the land or ocean, or the human body—is a recent quality control, annotation, and a logical structure
development but a copious producer of data. These must be imposed on it to make information retrieval
data illuminate one another. One story that they tell possible. For this we are indebted to the institutions
is about unsuspected underlying unities of all living that archive, curate, organize, and distribute the data.
things, despite the obvious and profound differences A trend has seen mergers of these groups into col-
in morphology and lifestyle. laborative projects spanning the continents. In accord
These genome data are the harvest of new and with the need to integrate the study of different types
more powerful DNA sequencing methods. Of course of data, we are moving in the direction of a large-
particular attention is focused on human genomes: scale unified biological data archive and repository.
several hundred thousand individual genomes are Conversely, individual scientists will be able to define
known. The goal of the US$1000 human genome has ‘virtual databanks’ tailoring access to the information
been achieved. This enterprise continues to grow: it to suit particular needs and interests.
is likely that during the lifetimes of many readers, Major changes in information distribution involve
human genome sequencing will be nearly universal the transition from paper to electronic libraries. The
in many countries. implications for scientific research are only a part
Genomic sequences are supplemented by other of the great social revolution that has flowed from
data streams. Patterns of gene expression, and the development of the Web; comparable to, if not
networks of regulatory interactions, show how cells exceeding, the one impelled by the printing press
and organisms implement the information in the 500 years ago. Only connect.
DNA. The potential for the life of an organism is The natural habitat of bioinformatics is the Web.
contained in its genome, but it would be impossible To achieve their scientific goals most projects begin by
to deduce a biography from it. Genomes are not identifying the relevant data on one or more websites;
formulae or scripts. It is in the RNAs and proteins, analysing them, usually applying tools available on
and their interactions amongst themselves and the Web; and reaching robustly justified conclusions;
with DNA, that we must seek the set of life’s ultimately leading to a publication also distributed on
activities, tragic and comic, contingent on and the Web. However, a serious problem with the Web
responsive to developmental programmes and/or the is its volatility. Sites come and go, leaving trails of
environment. dead links in their wake. Databases proliferate. Many
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

Preface to the fifth edition xix

new databases represent different ways of ‘slicing and available tools rather than creating new ones.
dicing’ information from other resources. Changes Many programs are freely available. As with
in a source database may trickle down slowly—or the data, the challenges are often to recombine
not at all—to derived resources. The resulting lack available programs. Constructing a cart requires
of consistency is a serious problem. not reinventing wheels, but assembling them.
It is necessary to try to find a few gateways that
Practitioners of bioinformatics must assimilate these
are stable: not only continuing to exist but also kept
attitudes and reflect them in their training.
up-to-date in both their contents and links. I have
Accordingly, there is somewhat more mention of
suggested some such sites, but many others are just
topics from computer science in this edition than in
as good. The problem is not to create a long list
the previous ones. This is in part because of critical
of useful sites—this has been done many times, and
comments received, but also because it is easier to use
is relatively easy—but to create a short one—this
these tools than before. Instead of needing to write a
is much harder! The site https://www.science.co.il/
sophisticated program, it is often possible to find an
biomedical/databases/ is comprehensive but useful.
available distributed one, or even a web server.
All research in contemporary biology and medicine
Indeed, one of the arguments for the suggestion
depends on data, and on programs to retrieve and
that sophisticated programming skills are not gener-
analyse them. There is consensus that all biomedical
ally required is the great panoply of freely available
scientists must achieve a minimum of programming
programs, written by acknowledged professionals.
skills, but there is vigorous debate over what this
What is essential is developing skill in using these
minimum level should be. In the preface to the fourth
programs, and in intelligent interpretion of the results
edition I wrote: ‘The point of view expressed in this
that they produce.
book is that molecular biologists based primarily
This is the goal of the problems and projects in the
in a “wet” lab must dip no more than their toes
the text and in the Online Resource Centre. Many of
into the stream; those based primarily at a computer
them are ‘weblems’ based on data and facilities on the
must wade in up to their waist perhaps; but only
web. Some are programming exercises. Some of these
those specializing in computer science and software
involve modifying programs. Such challenges can be
development must undergo total immersion.’ Today,
more focused than writing programs from scratch.
this appears as a gross understatement, given that:
Moreover, such exercises better exemplify situations
1. The growth in the amounts, and kinds, of that arise in actual research.
data. Traditional input streams, such as DNA Some of the exercises, problems, and weblems,
sequences; and novel ones, such as tissue- although not requiring any programming, can be
dependent inventories of RNAs (transcriptomics), solved more easily by writing short programs. Read-
produce torrential output. There is danger in ers are encouraged to try this approach whenever
adopting too-casual an attitude. appropriate.
The minimal computing skills essential for a
2. A revolution in approach to data has been the
biomedical scientist would also include facility
recognition that the structure of data is as impor-
with using social media for communication (it is
tant as the values (it would be going a bit too far
assumed that readers are familiar with Facebook and
to say more important).
YouTube, but there are others that are in use for
3. Different ways to recombine data provide novel communication among scientists), and the ability to
approaches. An example would be to combine create a website. Studying from this book and the
genome sequences with signatures of protein func- Online Resource Centre affords an opportunity to
tion to assign roles to gene products. practise these skills. You might, for instance, ‘turn in’
4. The data have elicited new sets of tools for the answers to homework assignments by gathering
analysis and application. The breadth of the them into a Web page. Questions about statements
software literature is so encompassing that that you and the other students found unclear in
research applications tend to involve the selecting your instructor’s lectures—or, conceivably, even in
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

xx Preface to the fifth edition

this book—could be shared and discussed in a blog. Bioinformatics is one of them. I have also written
Indeed, there is now a trend to integrating websites about genomics, and about proteins, in companion
and social media. However, there are security issues. volumes also published by Oxford University
Your instructor might be unhappy if everyone copied Press: Introduction to Protein Science: Architecture,
the answers to the exercises from the first student Function, and Genomics and Introduction to
to post them. A class taught from this book would Genomics. As a result, this book is focused more
afford a fine opportunity to explore the possibilities tightly on the applied science of bioinformatics.
and challenges. Readers are urged to put the books together
There are many different possible points of for a more rounded appreciation of the pageant
view from which to present molecular biology. of life.
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

PLAN OF THE BOOK

• Chapter 1 sets the stage and introduces all of the paper to electronic form. This transition has many
major players: DNA and protein sequences and consequences, both intellectual and practical. It
structures, genomes and proteomes, databases and has had profound effects on research in bio-
information retrieval, the World Wide Web, and informatics.
computer programming. Before developing indi- • Chapter 7 treats the topics of artificial intelligence
vidual topics in detail it is important to see the and machine learning. Few activities, even outside
framework of their interactions. science, have escaped applications of these meth-
• Chapter 2 presents the background of genetics ods. They are playing a role of growing importance
and genomes, and the development of DNA in molecular biology.
sequencing. • Chapter 8 introduces systems biology. The key idea
• Chapter 3 contains a survey and some important of systems biology is integration: how do all the
examples of genome sequencing. pieces fit together? How do they interact? How
• Chapter 4 treats the analysis of relationships among do the individual molecules and processes together
sequences: alignments and phylogenetic trees. create a whole that so far transcends the pieces in
These methods underlie some of the major compu- self-sufficiency?
tational challenges of bioinformatics: detecting • Chapter 9 describes metabolic pathways. The
distant relatives, understanding relationships activities of individual enzymes are the subject
among genomes of different organisms, and tracing matter of classical biochemistry. Understanding
the course of evolution at the species and molecular their controls has been a goal of molecular biology,
levels. revealing a variety of mechanisms at the levels
• Chapter 5 moves into three dimensions, treating of transcription, translation, post-translational
protein structure and folding. Sequence and struc- modifications, and the interaction of inhibitors
ture must be seen as full partners, with bioinfor- and allosteric effectors with enzymes themselves.
matics developing methods for moving back and The integration of these controls is a development
forth between them as fluently as possible. Under- of systems biology, as a continuation of Chapter 8.
standing protein structures in detail is essential • Chapter 10 deals with more general control
for determining their functions and mechanisms mechanisms, including gene expression. Control
of action, and for clinical and pharmacological of gene expression is involved in responses to
applications. stimuli and changes in the cell’s environment,
• Chapter 6 describes the current state of the and governs short- and long-term developmental
scientific literature as it makes the transition from processes.
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

INTRODUCTION TO BIOINFORMATICS ON THE WEB

Bioinformatics is intimately bound up with the World 3. Animations of structural diagrams.


Wide Web. This book is closely coordinated with 4. World Wide Web resources, to supplement treat-
its own website: http://www.oxfordtextbooks.co.uk/ ments of specific topics. Some of these sites imple-
orc/leskbioinf5e/. ment methods, such as sequence alignment, or
This site contains: homology modelling of protein structures. Others
1. References to all sites mentioned in the book, provide curated lists of links to other websites spe-
in context, so that the reader can link to them cialized to particular subjects, such as expression
directly instead of needing to type their locations. databases.
2. In previous editions, the weblems appeared in 5. In general, all material from the book that the
the text. These are now in the Online Resource reader would find useful to have in computer-
Centre. They have been developed and now fea- readable form, including data for exercises and
ture challenges with a range of difficulties, from problems, and all programs, now appears in the
relatively straightforward exercises to extended Online Resource Centre.
projects.
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi

ACKNOWLEDGEMENTS

I am grateful to many colleagues for discussions and T. Madden, J. Magré, M. McFall-Ngai, J. McInerney,
advice during the preparation of this book, and to the P. Miller, C. Mitchell, J. Moult, E. Nacheva, C.
universities of Uppsala, Umeå, Rome ‘Tor Vergata’, Notredame, C. Ouzounis, A.P. Pandurangan, H.
Bologna, and Cambridge for the opportunity to try Parfrey, D. Parkinson, A. Pastore, M. Peitsch,
out this material. D. Penny, J. Pettitt, C.A. Praul, C. Ravarani, S.
I thank S. Adhya, D.J. Abraham, S. Aparicio, Reikine, F.W. Roberts, G.D. Rose, P.B. Rosenthal,
M.M. Babu, T. Baglin, D. Baker, S. Balaji, M. B. Rost, B. Santhanam, E.J. Simon, M. Segal,
Bashton, A. Bateman, A. Bench, J.M. Bollinger, V. O. Skovegaard, G. Slodkowicz, E.L. Sonnham-
Bonazzi, M. Brand, A. Brazma, A. Buckle, C. Cantor, mer, R. Srinivasan, R. Staden, J. Sulston, I.
R.W. Carrell, S. Chavali, C. Chothia, D. Crowther, Tickle, A. Tramontano, A.A. Travers, A.R. Venki-
T. Dafforn, A. P. Diz, I. Dodd, R.B. Eckhardt, taraman, G. Vriend, P. Welsch, J.C. Whisstock,
J.G. Ferry, R. Foley, A. Friday, M. Galperin, M. Wildersten, A.S. Wilkins, S.H. White,
M.B. Gerstein, T. Gibson, J. Gough, J. Irving, B. V.E. Womble, and E.B. Ziff for advice and critical
Jorden, J. Karn, K. Karplus, P. Klappa, A.S. Kon- reading.
agurthu, E.V. Koonin, M. Krichevsky, P. Lawrence,
E.L. Lesk, M.E. Lesk, V.E. Lesk, V.I. Lesk, A. Lister, A.M.L.
L. Lo Conte, D.A. Lomas, A.D. MacKerell Jr, Cambridge, July 2018
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
Exploring the Variety of Random
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Title: Race Riot

Author: Ralph Williams

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Release date: February 15, 2019 [eBook #58893]

Language: English

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*** START OF THE PROJECT GUTENBERG EBOOK RACE RIOT ***


RACE RIOT
BY RALPH WILLIAMS

McCullough was not a native lover, nor was


he particularly bull-headed. He just felt there
was a certain difference between right and
wrong
and nobody was going to change his mind.
Take that Sunday afternoon....

[Transcriber's Note: This etext was produced from


Worlds of If Science Fiction, January 1955.
Extensive research did not uncover any evidence that
the U.S. copyright on this publication was renewed.]
The riot started late Sunday afternoon, in the alley back of John
McCullough's house. McCullough was in at the start of it, and he was
in at the end.
Sunday is thirty hours long on Centaurus II, as are all the other days
of the week, of course; and in summer, at the latitude of Port
Knakvik, the afternoons are very long indeed. John McCullough that
Sunday had finished hanging the windows in the log house he was
building, and now he was relaxing on the back stoop with a bottle of
local whiskey. The whiskey was distilled from a native starchy root,
and had a peculiar taste, but it was alcoholic, and one got used to it.
In the kitchen McCullough's wife was getting Sunday dinner on the
new inductor stove, still marvelling at its convenience—back on the
farm they had cooked with wood. The two children were playing in
and out of the house. His neighbors, Henry Watts from across the
street, and Pete Tallant from next door, had been helping him with
the windows, and now they were helping him with the bottle. They
were discussing the native question. In a way, this was the
beginning of the riot.
"It's not that I got anything against them, in their place," Henry
Watts said. "Their place just ain't in an Earthman's town, that's all.
They keep crowding in, first thing you know there'll be more natives
than there is Earthmen, then you just watch out. They're snotty
enough already in their sly way, you let them get the upper hand
once, mark my word, it won't be safe for a woman to walk down the
street."
"Yeah, I guess so," McCullough said. He was really not much
interested. His people were from the flats upriver from Knakvik, a
long-settled country where the first colonists had been brought two
generations before to form the nucleus of an agricultural community.
He had never seen more than half a dozen native Centaurans until
he came down to Knakvik to work on the spaceport the new federal
colonial government was building, and it was not his nature to worry
about problems which did not directly concern him. Mostly, he liked
to mind his own business, it was characteristic of McCullough that
his friends came to visit him at his house, he did not go to visit
them.
"What the government ought to do," Watts said, "it ought to take
the whole bunch and round them up and put them away on a
reservation somewhere. You can't civilize a grayskin, they ain't even
human to start with, so why try?"
"Nuts," Pete Tallant said. Where Watts was a redneck miner and
construction worker; and McCullough a farmer picking up a little
easy money on a temporary job; Tallant was an intellectual, a dark
restive young Earthman working his way around to see how Earth's
far colonies looked. Watts' yapping irritated him, but there was no
point in arguing against that sort of brainless conviction, he knew.
He stared gloomily off at the mountains across the river, rising clean
and snow-capped above the shanties and garbage piles of the
transient workers who had overflowed the city to camp on the flats
along the river; thinking:
Just over a hundred years ago this planet was first discovered by
men. Less than sixty years ago the first colonists were brought here.
They came to a brand-new planet, almost as naked as the day they
were born—two hundred pounds per colonist, including their own
weight—with a free hand to build a new world as they pleased. And
already the same old pattern, hate and distrust and envy, greed and
oppression. How many men on Centaurus II? Perhaps a hundred
thousand. How many native Centaurans? Perhaps five million, on a
planet larger than Earth. But not enough room for both—
"You think I'm prejudiced," Watts said heavily, the need of the
frontiersman to justify his opinions before the cosmopolite rankling
in his voice. "Well, I ain't. I just know those buggers, that's all. You
greenhorns come out here from Earth, you figure you got an answer
to everything, just because we don't have the schooling you got,
we're a bunch of fools. Ain't that right, John?"
"Yeah, I guess," McCullough said absently. The next thing to do, he
thought, now that they had inductor power from the central station,
was to get running water in the house. Plastic bubbles and tents and
shanties and hauling water from the pump were well enough for
bums and single men, but a family man might as well be building a
decent home while he was about it. There would always be rental
value in a good house here in town, especially with the new
spaceport and the government moving here; and later, when the
kids had to go to high school, it would be handy. Some day, too, he
would be retiring, turning the farm over to Jimmy, he and Mary
would need a place to live then.
"The old ones ain't so bad," Watts said. "They know their place, and
they remember what happened at Artillery Bluff. But some of these
young bucks, especially the smart-alecky kind the government has
been sending to school—" He shook his head forebodingly.
"Nuts," Tallant said wearily. "Let's talk about something we can all be
stupid about, huh? Women or baseball or something."
Watts flushed. "I know what I'm talking about now, and I didn't get
it out of books, either, I've lived with the buggers. You greenhorns
read all this sob stuff in the high-brow magazines back on Earth
about the noble Centaurans, and you figure we're a bunch of jerks
because we don't slobber all over them too. Noble Centaurans!
Jesus! Dirty, sneaking non-humans, that's what." He lifted the bottle
and drank deeply, tilting back his head and letting his eyes rove.
"There," he said abruptly. "There's your noble Centaurans, look at
'em!"
A group of natives were coming up the alley—in Port Knakvik,
natives did not walk in the street—shuffling along with downcast
eyes. They were a small gray-skinned people, roughly humanoid,
viviparous but not mammalian. There were five males followed half a
dozen steps behind by a female carrying an infant on her hip.
"You see that kish there with her fotin?" Watts asked. "Lemme show
you something, you probably wouldn't believe this if I told you,
these grayskins are just like animals, they got no decency at all." He
stood up and waved an arm in a beckoning gesture. "Hey, you kish,
come over here," he called.
The female Centauran paused uncertainly, looking at him with
frightened eyes out of a small triangular noseless face.
"Yes, you," Watts barked. "Come here!"
She glanced at the males ahead of her, who had also stopped and
were looking at Watts from the corners of their eyes. One mumbled
something to her. She began to shuffle slowly across the yard toward
Watts, looking at her feet. Watts took a steel five-dollar piece from
his pocket and held it out toward her.
"Here, you kish," he said, "feed baby, viptiv fotin, get money."
The native took the coin and looked doubtfully at the three men.
"Viptiv?" she asked in a light high voice.
"That's right," Watts said. "Viptiv fotin." He grinned at Tallant.
"Watch this, kid, you want to see your noble Centauran do
something'll really make you gag."
"Oh, for Pete's sake," Tallant said. "I know these people feed their
young by regurgitation. So it's disgusting to mammals? So what?"
He jumped down from the stoop and took the Centauran mother's
arm and turned her gently around. "No viptiv," he said. "Run along."
Watts' face was almost purple now. "What the hell you think you're
doing?" he shouted. He grasped the female's other arm. "Viptiv," he
gritted in her face. "You took my money, now viptiv!"
"Let go that woman," Tallant said, "or I'll push your face in." He
turned toward the group of males, who still stood stupidly staring.
"Come on over here," he called. "Take your woman and get out."
One of them started reluctantly across the yard. Tallant dropped the
native woman's arm and stepped past her to face Watts. "I told you
to let go," he said.
Watts thrust his face out. "Make me, wise guy."
Tallant hit Watts in the face with his fist.
Watts was a big man, and tough. He shook his head, wiped his nose,
looked incredulously at the blood on his hand, and let out a roar of
rage. It was not much of a fight. Watts' first blow dazed Tallant, the
second knocked him down, and before he could get up Watts
stepped in and kicked him in the head.
The Centauran woman still stood where the men had left her, wide-
eyed with confusion. She ran awkwardly over to Watts, shoving in
between him and Tallant's prostrate body, and pushed the five-dollar
piece at him, chattering excitedly in her own tongue. Watts twisted
the money from her fingers and shoved her roughly down on top of
Tallant. "There, you goddam native-lover," he roared, "get a real
good whiff of one once, see how you like it."
She was still carrying the baby, she tried to shield it as she fell, but
her body twisted and she came down heavily on it. The baby
screamed, a high-pitched, nerve-tearing sound. The male who had
started back to get her pulled a long sharp knife from somewhere
beneath his rags and broke into a trot, his eyes beadily intent on
Watts.
McCullough had started down off the porch when Watts put the boot
to Tallant. He changed his intent and ran in behind the native, and
hit him solidly with his fist in the back of the neck. The native went
sprawling and his knife flew out of his hand.
People were turning to look and popping out of tents and shelters all
around now.
"Why, that dirty native," Watts bellowed, "he tried to knife me!"
He stepped over to the Centauran and kicked him savagely several
times. The other four males had been watching open-mouthed. They
turned abruptly and started back down the alley the way they had
come, but there was a small knot of men there, watching them. The
natives paused uncertainly. One broke away and ran toward the
street, between McCullough's house and Tallant's tent, and the
others followed.
Most of the Earthmen had no idea what was happening. The closer
ones could see a couple of natives and a man lying on the ground,
another man with a bloody face shouting something about knifing,
and four natives running.
"Head 'em off!" someone called. "They'll get away in the street!"
That was how the riot at Port Knakvik started.

Watts ran off after the mob chasing the natives, perhaps with some
idea of explaining, more likely not—he was in a half mindless rage of
excitement with the whiskey and the fighting. McCullough was left
alone with Tallant and the two natives. The native woman seemed
unhurt, she was picking herself up and examining the infant, which
still whimpered. Tallant was unconscious. McCullough picked him up
and carried him into the house.
His wife was standing white-faced at the door.
"Get some water," he said. He laid Tallant on a cot and began to
wipe off his face. There was a scalp cut where Watts' boot had
clipped him, most of the blood was coming from that; but it was
high and it did not feel like a fracture. Presently Tallant groaned and
shook his head and opened his eyes. The pupils did not look bad.
"How do you feel?" McCullough asked.
"Rough," Tallant mumbled. "Rough. Side ... hurts...."
McCullough pulled up the shirt and looked. There was a swelling
purplish bruise on the chest. He touched it gently and drew a gasp
of pain.
"Looks like maybe you got a cracked rib," he said. "Get me some
tape, will you, Mary?" He took the roll of tape and wound it tightly
about Tallant's chest.
"That'll hold till you get to a doctor," he said.
Tallant drew a light experimental breath. "Feels better," he said.
"What the hell happened anyway?"
McCullough told him.
"That's bad," Tallant said. "That fool Watts could touch off a real riot,
there's plenty more around here with no more brains than he has,
and just spoiling for trouble. Somebody ought to get the marshal's
office working on it before things get out of hand." He took the wet
rag he had been holding to his head away and examined the cut
with squeamish fingers. "Have to get this stitched up too, I guess,
before it sets up hard. Look, could you back my truck out into the
street? I don't feel up to driving, but if I get it in the street, it can
take me in to the dispensary on auto, and I can call Administration
from there."
There were very few private vehicles in Port Knakvik, or indeed
anywhere on Centaurus II; but Tallant, who was an electrician, had
a company panel which he drove to and from the job. Though it was
chemically powered—the new inductor station was the first nuclear
installation on the planet—it had the same cybernetic controls as any
Earthside vehicle. They worked fine on paved roads. On Knakvik
streets, however—
"I don't know," McCullough said dubiously, "You think you can make
it on auto? Suppose you get stalled?"
Port Knakvik lay on a silty alluvial plain. In the downtown area, the
streets were stabilized, but back along the river where the shanties
of the construction workers sprawled, they were simply ruts
punctuated at frequent intervals by chuckholes where churning
wheels had ripped off the overburden, exposing the bottomless
muck beneath.
"I'd go with you," McCullough said, "except I kind of hate to leave
Mary and the kids right now—I tell you, maybe I could find
somebody else. You lay down for a minute, take it easy, I'll look
around."
Tallant seemed to have guessed right about the riot, there were
people running by outside toward a commotion at the lower end of
the street where the native shanties clustered. McCullough saw a
man he knew from the job. "Hey, George," he called, "you got time
to do a little favor?" He explained about Tallant.
The man had not yet been in any fighting, he was simply curious
about what was going on, and this was part of it. "Sure, John," he
said. "Be glad to."
They helped Tallant into the truck. George backed it out into the
street on manual. "What's the dispensary coordinates?" he asked.
"Three-two-three, oh-one-five, local," Tallant told him.
George pushed the keys and they started off toward town.
McCullough turned to see what he could make out of the excitement
at the other end of the street. There were two columns of smoke
billowing up now, and scattered shots. Two men came back up the
street helping another with his trouser leg split away and a bloody
bandage about his thigh.
"What's it all about, John?" A man called across the street to him.
"Don't know. Fighting with the natives, I guess. Henry Watts and
some other fellows chased a couple of them down there. Looks like
they mean to clean the whole bunch out."
"Dammit, that's not right," the man across the street said. "The
natives got a right to live too, they had a village here before we
came. Somebody ought to do something about it."
"Pete Tallant just went into town to tell the marshal."
"Yeah, well, I wouldn't holler copper on my neighbors myself, but I
won't have anything to do with killing those poor natives either. They
can get along without me." The man went back in his house and
closed the door.
McCullough walked a few steps out into the street to get a better
view. The riot was none of his business, and he had no intention of
getting mixed up in it, but the idea of the fighting excited him and
made him nervous. He could not see much, except that there was a
lot of activity.
He shook his head helplessly. My God, he thought, all this from two
men with nothing to do on a Sunday afternoon but get half-drunk
and start arguing....

Someone screamed—Mary's scream, suddenly choked off!


McCullough ran back across the yard and up the steps, raging at
himself for having left Mary and the children alone in the house.
There was no one in the front room, but through the kitchen door he
could see a native with his back turned, peering out the kitchen
window.
McCullough's gun was hanging over the door, on pegs set into the
logs, a gun made from the first steel smelted on Centaurus II. He
reached down the gun as he stepped in the door.
There were two natives in the kitchen; one with a roughed-up look
who might have been the one Watts had kicked, watching Mary as
she huddled in a corner by the stove with her arms about the two
children; the other still looking out the window. Both spun around to
face him as McCullough burst into the room.
For a moment they eyed each other in silence, the two Centaurans
and the Earthman.
"You hurt, Mary?" McCullough asked.
She was frightened almost speechless, but she managed a squeak
and a negative shake of her head.
McCullough took his eyes from the natives for a moment and studied
her searchingly. "You sure?" he asked. She nodded. Some of the
color was coming back in her face again now, and she looked all
right.
He looked back at the two natives. He should have them arrested,
he supposed, but to file a complaint meant going to court and losing
a day's work. It did not even occur to him to hold them for the mob.
He gestured with the gun muzzle. "OK," he said roughly. "Get out of
here, now. Get!"
The natives looked at each other. Outside, there was a rattle of shots
in the alley, and several high-pitched screams. The native by the
window wet his lips and shook his head, and the other turned back
toward McCullough. He had a knife in his hand, which he swung
menacingly.
"No," he said. "No go outside. Kill."
It was not clear if he meant the verb passively or actively, but with
the knife not six feet from Mary and the children, it did not seem a
proper time to discuss fine points of grammar. McCullough shot him
in the belly. At that range, the charge almost tore the slight native in
half.
The other Centauran turned and came lunging toward him, and
McCullough fired again. The native stumbled and fell in a heap in the
middle of the floor, half across the body of the first.
McCullough stepped over them to the back door and glanced out,
dropping fresh charges in the gun as he did so. There were no
natives in sight but several white men were in the alley, looking
around, trying to decide where the shots had come from. Henry
Watts was with them. He saw McCullough at the door and called out
to him: "You hear those shots? Two of 'em ran back up this alley.
You see them?"
"They came in my house," McCullough said. "I shot both of them."
"Good, by God," Watts yelled. "That's two we don't have to worry
about."
"There's one more left," another man called from up the alley. "He
ducked around through Gordon's lot."
The men ran off up the alley on the new scent, and McCullough
turned back into the kitchen. Mary had collapsed into a chair and
was sobbing with her head in her arms. The two children clung to
her, staring wide-eyed at the bodies of the natives.
McCullough walked over and patted her on the back. "It's OK now,
Mary," he said. "It's OK, nothing to worry about now." His wife went
on crying, and he stood there awkwardly, not quite knowing what to
do.
He noticed that the dark purplish blood of the natives, almost black,
was spreading in little rivulets and pools over the kitchen floor. The
floor was of sanded white wood, and stained easily. There were
some folded tarps in the lean-to where McCullough kept his tools. He
got one and rolled the bodies over onto it. As he did so, he saw that
one of them, the second one he had shot, was still alive. The shot
had gone low and mangled the native's upper leg. He stared up at
McCullough with opaque expressionless eyes, slowly bleeding to
death.
It was an embarrassing situation. McCullough was not any more
callous than the next man, but he found himself wishing his aim had
been better. He could hardly allow the Centauran to lie there and
bleed to death while he watched, but neither did he feel any
particular responsibility in the matter. The native had got what he
was asking for, and that was that.
Finally he took the native's leather belt and tightened it around the
leg for a tourniquet, got another tarp and spread it on the cot, and
laid the native on it. The corpse he rolled in the first tarp and pushed
under the cot. Throughout the injured Centauran said nothing, either
in thanks or protest, although the leg must have been painful.
He had just finished when he heard voices in the front yard.
Henry Watts was there with half a dozen other men carrying guns
and clubs, all looking the worse for wear. Two were dragging a
Centauran corpse by the pants legs.
Watts mopped at his sweaty, blood-stained face with his shirt-tail.
"You still got those two grayskins in there?" he asked.
McCullough nodded.
"Fine, we'll take 'em off your hands now." Watts half-turned to the
men behind him. "Come on, give me a hand to drag 'em out." He
started up the steps.
"Wait a minute," McCullough said. He did not move out of the door,
he was not quite sure why, a moment ago he had been wondering
what to do with the natives, and here was Watts offering to take
them. It may have been the way they were dragging the Centauran,
face down in the mud, that bothered him. "What you going to do
with them?" he asked.
"We got a use for 'em," Watts said with relish. "We're going to drag
all the bodies up in front of Dubois' place and string 'em up to poles
there, for a warning. We'll learn those grayskins what to expect, they
come messing around here any more. Come on, toss 'em out, we'll
take these two along with the rest."
"Well, I don't know," McCullough said. "One of these is still alive, I
didn't kill him, just crippled him."
Watts showed his teeth. "That won't be a problem," he said.
McCullough shook his head slowly. He had counted Henry Watts as
his friend, but he was not so sure now that he liked him. "No," he
said. "I think we better just leave them till the cops come."
Watts laughed. "Cops? There ain't going to be any cops coming.
We're handling this ourselves. Don't worry about the cops, even if
they could get an indictment, there ain't a jury in this town would
convict for killing a native."
"I'm not worrying about that," McCullough said stolidly, "but I don't
like what you fellows are doing, I might as well say right now, and
I'm not going to be a party to it. Those natives stay right where they
are till the law comes and gets them."
Watts' grin faded. "John," he said, "we ain't fooling. I know you're no
native-lover, but we're going to clean those devils out once for all. If
you won't let us in for them, we'll come in anyway and take 'em."
McCullough shook his head again. "This is my house. Henry, you've
been my friend, but I just shot two people for coming in here
without knocking."
Watts looked around at the men behind him. Most of them knew
McCullough. They did not seem taken with the idea of breaking into
his house. Watts swung back to McCullough. "John," he said
ominously, "you're just making trouble for yourself, that's all."
McCullough simply shook his head and stood blocking the doorway.
Watts glanced around at the other men again. One of them
shrugged self-consciously and turned away, and after a moment the
others trailed after.
"All right," Watts growled. He shook his fist under McCullough's
nose. "All right, John McCullough, I'll remember this, and I'll be
back. Native-lover!" He spat on the step and went off after the
others.
McCullough watched them go, uneasy under his surface stolidity. He
liked to be on good terms with his neighbors, not enough to give in
to them on anything he felt strongly about, but he knew this would
be held against him, and it worried him, more for the sake of Mary
and the kids than for himself.
He sensed his wife standing behind him.
"What did they want?" she asked.
He told her.
"But, John, why? Haven't we had enough trouble today? Do you
have to get in a fight with your neighbors over a stupid native? What
difference does it make to you?"
McCullough shook his head helplessly. "I don't know. I just don't like
the idea, that's all."
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