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Chapter 1. Introduction
1.1. WHAT IS A GENE?
Contents
1.1. What is a Gene?
1.2. What is a Genome?
1.3. What is Genomic Biology?
1.3.1. Structural Genomics
1.3.2. Comparative Genomics
1.3.3. Functional Genomics
1.4. Genomic Databases
 CHAPTER 1. INTRODUCTION
To begin our study of genomic biology we need to
gain a common vocabulary with which we can move
forward. At this point the definitions should come from
your background knowledge equivalent to a beginning
biology course. If these definitions are unfamiliar, you
will need to refresh them using either the enclosed
hyperlinks or a general biology or genetics textbook. As
we move forward with our study of genomic biology all
of these definitions will become more refined and more
meaningful, so that by the end of the course you might
wish to use a more thorough definition than our
beginning point here.
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What is a Gene? There are really two definitions of a
gene that could be given. These are:
Classical genetic definition – A gene is the unit of
heredity that carries genetic information that
produces the trait of an organism from one
generation to the next. Subsequently, it has been
demonstrated that genes reside on chromosomes,
and chromosomes are passed from one
generation to the next.
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Molecular genetic definition - A gene is a locatable
region of genomic sequence, usually associated
with a chromosome, corresponding to a unit of
inheritance, which is associated with regulatory
regions, transcribed regions, and or other
functional sequence regions ultimately generating
a phenotypic trait. The diagram below describes
some of these terms, but for now you only need
understand that a gene can be defined in terms of
specific DNA sequences residing on the DNA
molecule carrying genetic information that is part
of the chromosome.
Note that the molecular definition of a gene suggests
that there is a region of a chromosome on which a gene
resides within something called a genome. This
definition draws on our background in cell biology and
genetics that we have learned about in other courses.
We will expand on this further in the remainder of the
book.
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1.2. WHAT IS A GENOME?
What is a Genome?
The term genome originated in the early part of the 20th
century apparently as a combination of the terms gene
and chromosome. It was originally meant to indicate
the sum of all of the genes on all of the chromosomes of
an organism, or alternatively, the entire set of
hereditary information for building, running, and
maintaining an organism (or virus). As such the
definition of a genome applies to all living things
including:
Figure 1.2. The parts of the Gene in the DNA sequence. This sequence
is coded for during translation to produce a pre-mRNA which is
processed into an mRNA that can be translated to produce a protein.
CONCEPTS OF GENOMIC BIOLOGY
Viruses
Prokaryotes
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Archaea
terms of DNA itself. What we know is that an organisms
genome is made up of chromosomes, that
chromosomes carry genes, and that DNA is the
substance carrying the information of the genes.
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1.3. WHAT IS GENOMIC BIOLOGY?
Eukyotes
Note that of these various groups of organisms some
have a genome consisting of but a single chromosome,
while others (mostly Eukaryotes have genomes made
up of multiple chromosomes. Further note that most
Eukaryotic organisms have organelles such as
chloroplasts and/or mitochondria that each contain
separate genomes from the nucleus.
Once it was determined that DNA carries the genetic
information that makes up genes and that this was
physically the basic substance required to produce the
traits that we all have, genomes took on a definition in
There is more to genomic biology than merely
obtaining the genetic information carried in DNA
molecules (sequence of base pairs in the DNA). There is
other important information required for a gene to
specific a trait, for example, other information is
sustained in each cellular generation at the
chromosomal level, and finally the genome as a whole
produces interactions that further determine gene
function and the influence of the environment on the
expression of genes.
Thus, the study of genomic biology must incorporate
not just the simplicity of DNA as the informationcarrying molecule, but also the myriad of complex and
sophisticated interactions between all things inside
biological systems that mediate the complex regulation
of that simple genetic information.
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To organize our study of the genomic universe,
typically 3 sub disciplines are considered. These are:
structural genomics, the techinques, strategies, and
analysis of primary genomes of organisms; comparative
genomics, the comparison of genes and genomes from
an array of related or unrelated organisms; and
functional genomics, understanding the factors that
mediate the function of genes. A brief overview of
these subdisciplines is given below.
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1.3.1. Structural Genomics
Structural genomics (Genome Structure) may be the
original definition of genomics that involves the
application of recombinant DNA technology, DNA
sequencing methods, and bioinformatics to sequence,
assemble, and analyze the complete structure of
genomes. Advances in genomics have triggered a
revolution in discovery-based research. The field
includes efforts to determine the entire DNA sequence
of organisms and fine-scale genetic mapping.
Because structural genomics has a heavy reliance on the
sequencing of complete genomes this area of genomics
has evolved rapidly as DNA sequencing technology has
evolved. A parallel emphasis on com-puter algorithms
for assembling shorter sequences obtained from
Figure 1.3. Structural genomics involves
primary DNA sequencing. This is a
compomparison of the output from
dideoxy Sanger sequencing showing
either black and white or color outputs.
modern DNA sequencers has allowed the rapid
development of genomic sequencing and a tremendous
lowering of sequencing costs.
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1.3.2. Comparative Genomics
Comparative genomics is a subdiscipline of genomic
biology in which the genomic features of different
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organisms are compared. Genomic features may include
the DNA sequence, genes and gene order, regulatory
sequences, and other genomic structural features. In
this branch of genomics, whole or large parts of
genomes resulting from genome sequencing projects
are compared to study basic biological similarities and
differences as well as evolutionary relationships
between organisms.
The major principle of comparative genomics is that
common features of two organisms will often be
encoded within the DNA that is conserved through
Figure 1.4. The interrelationships of all living
organisms to eachother can be investigated at
the DNA sequence level. One of the results of
this effort is the Tree of Life Project. This
project is an outstanding example of the power
of comparative genomics.
(evolutionary) time. Therefore, comparative genomic
approaches typically begin by making some form of
sequence alignment of genome sequences and looking
for orthologous sequences (sequences that share a
common ancestry) and checking the extent that those
sequences are conserved. Based on this orthology, the
genome and molecular evolution of the genomes are
made and interpreted in the context of, for example the
phenotype of the organism or in the context of the
genetics of whole populations.
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1.3.2. Comparative Genomics
Comparative genomics is a subdiscipline of genomic
biology in which the genomic features of different
organisms are compared. Genomic features may include
the DNA sequence, genes and gene order, regulatory
sequences, and other genomic structural features. In
this branch of genomics, whole or large parts of
genomes resulting from genome sequencing projects
are compared to study basic biological similarities and
differences as well as evolutionary relationships
between organisms.
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1.3.3. Functional genomics
Functional genomics is the subdiscipline of genomic
biology that focuses on how genes and genomes
function. Once the genes in a genome are discovered
by DNA sequencing (such as genome sequencing
projects) functional studies seek to describe gene and
protein functions. Functional genomics focuses on the
dynamic aspects of the genome, such as gene
transcription,
translation,
and
protein–protein
interactions, as opposed to the static aspects of the
genomic information such as DNA nucleotide sequence
or structures. Functional genomics attempts to answer
questions about the function of DNA at the levels of
genes, RNA transcripts (transcriptomics), and protein
products (proteomics). A key characteristic of functional
genomics studies is their genome-wide approach to
these questions, generally involving high-throughput
methods such as microarrays (see below) rather than a
more traditional “gene-by-gene” approach.
The goal of functional genomics is to understand the
relationship between an organism's genome and its
phenotype. Functional genomics involves studies of
natural variation in genes, RNA, and proteins over time
(such as an organism's development) or space (such as
its body regions), as well as studies of natural or
experimental functional disruptions affecting genes,
chromosomes, RNA, or proteins such as environmental
stresses.
The promise of functional genomics is to expand and
synthesize genomic and proteomic knowledge into an
understanding of the dynamic properties of an organism
at cellular and/or organismal levels. This would provide
a more complete picture of how biological function
arises from the information encoded in an organism's
Figure 1.5. A colorized microarray. Colors represent
different levels gene expression. Microarras are used to
examine genomewide gene expression data.
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genome. As such functional genomics is the major
ongoing focus of genomic biology today, and although
we have learned a great deal about gene function, much
remains to be learned.
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1.4. GENOMIC DATABAES
Much of the structural, comparative, and functional
genomic information is collected into various databases.
There are many international specialty database-sites
that are available, but the largest single database is the
National Center for Biotechnology Information (NCBI)
database at the National Library of Medicine (NLM)
sponsored be the National Institutes of Health (NIH).
Figure 1.6. A colorized microarray. Colors represent
different levels gene expression. Microarras are used to
examine genomewide gene expression data.
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