Download Chapter 1. Introduction

Chapter 1. Introduction
Contents
1. Introduction
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
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1.1. WHAT IS A
GENE? (RETURN)
What is a Gene? There are really two definitions of
a gene that could be given. These are:
 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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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.
1.2. WHAT IS A
GENOME? (RETURN)
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.
Viruses
Prokaryotes
Archaea
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1.3. WHAT IS
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 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.
GENOMIC BIOLOGY? (RETURN)
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
information-carrying 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.
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
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the factors that mediate the function of genes. A
brief overview of these subdisciplines is given below.
1.3.1. Structural Genomics
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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
computer algorithms for assembling shorter
sequences obtained from modern DNA sequencers
has allowed the rapid development of genomic
sequencing and a tremendous lowering of sequencing
costs.
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.
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1.3.2. Comparative Genomics (return)
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.
The major principle of comparative genomics is
that common features of two organisms will often be
encoded within the DNA that is conserved through
(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
1.3.3. Functional genomics
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.
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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
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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 genome. As such functional
genomics is the major ongoing focus of genomic
Figure 1.5. A colorized microarray. Colors represent
different levels gene expression. Microarras are used to
examine genomewide gene expression data.
biology today, and although we have learned a great
deal about gene function, much remains to be
learned.
CONCEPTS OF GENOMIC BIOLOGY
1.4. GENOMIC DATABAES
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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.