Chapter 1. IntroductionContents

1.1. What is a Gene?1.2. What is a Genome?1.3. What is Genomic Biology?

1.3.1. Structural Genomics1.3.2. Comparative Genomics1.3.3. Functional Genomics

1.4. Genomic Databases

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.

CHAPTER 1. INTRODUCTION

1.1. WHAT IS A GENE?

CONCEPTS OF GENOMIC BIOLOGY Page

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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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.

1.2. WHAT IS A GENOME?

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CONCEPTS OF GENOMIC BIOLOGY Page

Viruses Prokaryotes Archaea

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.

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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.

1.3. WHAT IS GENOMIC BIOLOGY?

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CONCEPTS OF GENOMIC BIOLOGY Page

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

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 GenomicsComparative genomics is a subdiscipline of genomic biology in which the genomic features of different

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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CONCEPTS OF GENOMIC BIOLOGY Page

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 .

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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

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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CONCEPTS OF GENOMIC BIOLOGY Page

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

genome. As such functional genomics is the major ongoing focus of genomic biology today, and although

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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CONCEPTS OF GENOMIC BIOLOGY Page

we have learned a great deal about gene function, much remains to be learned.

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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).

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1.4. GENOMIC DATABAES

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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