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Biology 205 Spring 2008

During the past several years, molecular geneticists and cell biologists have announced (usually with great fanfare and attention from the popular press) specific accomplishments with respect to the study of biology and medicine

Biology in the Popular Press: What topics have caught your eye? What do you know about the topic? Why should we care as biologists or as ordinary citizens?

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Biologists of the 21st century live in privileged times

In other words we now have unprecedented amounts of data about these resevoirs of genetic information

Over the past decade or so the complete genome sequences of representatives from all the major groups of organisms on Earth have been determined and many more genome projects are underway

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These organisms were among the first to have their genomes sequenced. But who else is in the priviledged category?

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome The Genome database provides views for a variety of genomes, complete chromosomes, sequence maps with contigs, and integrated genetic and physical maps. The database is organized in six major organism groups: Archaea, Bacteria, Eukaryotae, Viruses, Viroids, and Plasmids and includes complete chromosomes, organelles and plasmids as well as draft genome assemblies.

Is(has) the genome of your favorite organism being(been) sequenced? Let’s check here: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genomeprj or here http://www.ncbi.nlm.nih.gov:80/genomes/static/EG_T.html

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Genome: • the collection of instructions that

specifies a given species • the entire genetic complement of an

organism • the collection of genes that specify an

organism • the DNA sequence that specifies an

organisms What is a gene?

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What is a gene? Mendelian definition of the Gene: the fundamental functional unit of heredity, which carries information from one generation to the next Biochemical definition of the Gene: a unit of heredity that specifies a protein Molecular definition of the Gene: segment of DNA composed of a transcribed region and adjacent regulatory region that control transcription We will explore each of these definitions over the next several weeks

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What is meant by the DNA sequence?

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What is meant by the DNA sequence? the complete order of monomer units in the DNA polymers that make up the genome >gi|17488858|ref|XM_010627.4| Homo sapiens SRY (sex determining region Y chromosome) GGCATGTGAGCGGGAAGCCTAGGCTGCCAGCCGCGAGGACCGCACGGAGGAGGAGCAGGAGCGCGGAGCC GCGAGCCCCGAGCCCCGAGCCCGGCGCCTGGCTGAGTAGATGTCCATGAGGAGCCCCATCTCTGCCCAGC TGGCCCTGGATGGCGTTGGCACCATGGTGAACTGCACCATCAAGTCAGAGGAGAAGAAAGAGCCTTGCCA CGAGGCCCCCCAGGGCTCAGCCACTGCCGCTGAACCTCAGCCTGGAGACCCAGCCCGGGCCTCCCAGGAT AGTGCTGACCCCCAAGCTCCAGCCCAGGGGAATTTCAGGGGCTCCTGGGACTGTAGCTCTCCAGAGGGTA ATGGGTCCCCAGAACCCAAGAGACCAGGAGTGTCGGAGGCTGCCTCTGGAAGCCAGGAGAAGCTGGACTT CAACCGAAATTTGAAAGAAGTGGTGCCAGCCATAGAGAAGCTGTTGTCCAGTGACTGGAAGGAGAGGTTT CTAGGAAGGAACTCTATGGAAGCCAAAGATGTCAAAGGGACCCAAGAGAGCCTAGCAGAGAAGGAGCTCC AGCTTCTGGTCATGATTCACCAGCTGTCCACCCTGCGGGACCAGCTCCTGACAGCCCACTCGGAGCAGAA GAACATGGCTGCCATGCTGTTTGAGAAGCAGCAGCAGCAGATGGAGCTTGCCCGGCAGCAGCAGGAGCAG ATTGCAAAGCAGCAGCAGCAGCTGATTCAGCAGCAGCATAAGATCAACCTCCTTCAGCAGCAGATCCAGC AGGTTAACATGCCTTATGTCATGATCCCAGCCTTCCCCCCAAGCCACCAACCTCTGCCTGTCACCCCTGA CTCCCAGCTGGCCTTACCCATTCAGCCCATTCCCTGCAAACCAGTGGAGTATCCGCTGCAGCTGCTGCAC AGCCCCCCTGCCCCAGTGGTGAAGAGGCCTGGGGCCATGGCCACCCACCACCCCCTGCAGGAGCCCTCCC AGCCCCTGAACCTCACAGCCAAGCCCAAGGCCCCCGAGCTGCCCAACACCTCCAGCTCCCCAAGCCTGAA GATGAGCAGCTGTGTGCCCCGCCCCCCCAGCCATGGAGGCCCCACGCGGGACCTGCAGTCCAGCCCCCCG AGCCTGCCTCTGGGCTTCCTTGGTGAAGGGGACGCTGTCACCAAAGCCATCCAGGATGCTCGGCAGCTGC TGCACAGCCACAGTGGGGCCTTGGATGGCTCCCCCAACACCCCCTTCCGTAAGGACCTCATCAGCCTGGA CTCATCCCCAGCCAAGGAGCGGCTGGAGGACGGCTGTGTGCACCCACTGGAGGAAGCCATGCTGAGCTGC GACATGGATGGCTCCCGCCACTTCCCCGAGTCCCGAAACAGCAGCCACATCAAGAGGCCCATGAACGCCT TCATGGTGTGGGCCAAGGATGAGCGGAGGAAGATCCTGCAAGCCTTCCCAGACATGCACAACTCCAGCAT CAGCAAGATCCTTGGATCTCGCTGGAAGTCCATGACCAACCAGGAGAAGCAGCCCTACTATGAGGAACAG GCGCGGCTGAGCCGGCAGCACCTGGAGAAGTATCCTGACTACAAGTACAAGCCGCGGCCCAAGCGCACCT GCATCGTGGAGGGCAAGCGGCTGCGCGTGGGAGAGTACAAGGCCCTGATGAGGACCCGGCGTCAGGATGC CCGCCAGAGCTACGTGATCCCCCCGCAGGCTGGCCAGGTGCAGATGAGCTCCTCAGATGTCCTGTACCCT CGGGCAGCAGGCATGCCGCTGGCACAGCCACTGGTGGAGCACTATGTCCCTCGTAGCCTGGACCCCAACA TGCCTGTGATCGTCAACACCTGCAGCCTCAGAGAGGAGGGTGAGGGCACAGATGACAGGCACTCGGTGGC TGATGGCGAGATGTACCGGTACAGCGAGGACGAGGACTCGGAGGGCGAAGAGAAGAGCGATGGGGAGTTG GTGGTGCTCACAGACTGATCCCGGCTGGGTGGGCCTGGCCCCTTCTCCTCTGGGGAAGACCTTGTCCCAA CTCGATGGGCACAGCCAGCCAACCTAAGACTATGTTGGTACTTGGACTTGTTCGTGCCCCAGAGATGGGC AAAGCTGTGCACTTGCAGATACATTCATGAGGGGAGAGGCGCCCTCCCTTCCTGAGGAGCTGTTGGCCTG GGTGGGCAGGAACTGCAGTATGGCCATGGGCTGAGCAGGCTGAGCACCTCAGCCTTTAGGGCTTATGGCC AGGGGACACTGTATGACTCTCCTCTCCTGCAGGTGTCTATCCACCTGGGGTATGGCATCTACCGACCTGT CTCCCTGGGGTCACATGCTTTGTTTCCATTCTTGTCCTGGCTGGACCAGCCACTGTGGGACCAACACCCC TCCCACACTCCCCCAGACTGCTCGTCTATCACCAGGATCGCTTTGTACTTTGTGCAAAAGGGTCTGGCTG TCCCTTGCTGTTTTCATCTCTGCCAAGCCTATTGTGCCTCTGGCTGCTGTATGTGTGCGCGTGCACGTGT GTGTGTTTCATCTGTTCATTCACTGCACAAGATATTTATTGAGTGCCCACTACGTGCCAGGCACTGTTGC TGAGTTCCTGTGGGTGTGTCTCTCGATGCCACTCCTGCTTCTCTGGGGGCCTCTTTCTGTGCTTCTCTTT GTCCCCAAATTGCTACCTCTTTGTCAGTCTGGGTGTCTCAGGTTCTGTGTGTCCTTGTGTGCATTTCTGT CTCTCTCTGTCCTCGTCTCTCTGCAAGGCCCTCTATTTCTCTCTTTCTTGGTGTCTGTCCTTTGCCCCCT GTGCCCTCTGGATTCTCTGGGTCTATGTAGGCCCCTGGTCTGCCCTGGGCTCATCAGCCTTCCTGACCTC CTCCTGCCCTCCCCTTCACTCCCTCCCTGGCTCTGCCAGTCGGTTCCCACGGAGCCATTTTTAGCTCTGA TCAGCATGGGAATGTGCCTCGGCCTCCAAGGGGCTTTGTCCTGGTGCCCCCGCCCCTGGTCCCAACCTGA

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Huh? to understand what a DNA sequence is and to understand this last definition of the gene, we must look at the biochemistry of DNA and protein polymers and how they relate to the genome projects

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So what are the Genome Projects? Huh? What? Who cares? Why? Project goals: • To determine the complete sequence of the 3 billion DNA subunits (bases) that are contained in one complete copy of the human genome: two rough drafts have been completed and high quality sequence is available for some chromosomes • To identify and understand the function of all of the approximately 25,000-30,000(?) human genes • As part of the Human Genome Project, parallel studies have been carried out on selected model organisms • The genomes of many other organisms are also being studied What is a chromosome? What does a chromosome have to do with DNA? What does it have to do with a genome?

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What have we learned from the completed genome projects? What sort of genetic information is contained in the genome of these organisms? What sorts of activities do genes control? The genome projects: http://www.ornl.gov/hgmis/ Click below for an optional reading assignment on the genome projects http://fire.biol.wwu.edu/trent/trent/genomeproject.pdf

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In order to address these questions, we need to consider the following questions: How does a living system differ from one that is not alive? What essential characteristics are found in all living systems yet known? What does a cell need to do to be alive?

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EAT: translates into Metabolism Living matter has the ability to accumulate, convert and transform nutrients and energy SURVIVE: Homeostasis -- a way to respond to stress, that is the maintenance of the physical structure under stress Response to external stimuli (from the environment) by individuals cells and organisms REPRODUCE Living matter must have a hereditary mechanim for transferring its properties to offspring

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Three essential characteristics found in all living systems known: Metabolism

• organisms must be able to transform energy • chemical reactions in a living system follow a controlled

program operated from an information center (genome) • these chemical reactions maintain an ordered, stable

cellular system • without metabolism the biological system would regress

to equilibrium Self-reproduction

• a living organism must propagate itself (and its genetic program)

• without self-reproduction, the information would be lost after each generation Mutation

• living organsims evolve • without mutation the genome is ‘unchangeable’ and

hence variation cannot arise Optional reading assignment click below to see an essay on the definition of life from Science 295: 2215 March 22, 2002 The Seven Pillars of Life http://fire.biol.wwu.edu/trent/trent/life.pdf

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Back to the original question: What sort of genetic information is contained in the genome of us and chimps and all of these organisms? The genetic information contained in the genome confer the ability of living organisms to transform energy, to reproduce, to maintain an ordered structure, to respond to the environment and so on… So, the categories of genes found in all genomes must reflect the essential characteristics of living systems

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The Arabidopsis thaliana (weedy plant) genome project was recently completed. Here is a breakdown of the functional analysis of the genes discovered in the genome of this organism. Note that a large proportion of the genes are unclassifed -- meaning no one knows yet what they do for the organism.

Nature 408: 796 Dec. 14, 2000

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A short digression: Biodiversity and species number How many different species are there on earth?

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Nature 418: 362 July 25, 2002 “ there is currently no concensus on the total number of species: estimates range from 4 million to 100 million….. roughly 1.7 million organisms have been named and formally described”

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Figure 4 Species richness in major groups of organisms. The main 'pie' shows the species estimated to exist in each group; the hatched area within each slice shows the proportion that have been formally described. Data from ref.

Nature 405: 212 May 11, 2000

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Some Organisms with sequenced genomes

Arabidopsis thaliana: a weed

Saccharomyces cerevisiae: yeast

Caenorhabditis elegans: free-living roundworm

Drosophila melanogaster

What question comes to mind when you view these organisms?

Esherichia coli: a gut bacteria

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We can’t study all organisms, so we single out a collection of “model” organisms to study model organism: a label we apply to species that biologists (i) study in detail (ii) use as a basis for constructing a general understanding of how biological processes work Reasons for choosing these particular organisms : • some practical - • some serendipitous • some carefully considered • some related to the importance of the organism

to human health and welfare (or commercial value)

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Almost everything we know about the fundamental properties of living cells – how they grow and divide, how they express their genetic information, and how they use and store energy—has come from the study of model organisms How can this be? Why is a fly or a worm a credible model system for humans or other organisms?

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We can justify the use of these organism based on practical arguments (limited time, space, money, etc.) But how do we establish the biological (theoretical) credibility for using studying these organisms This argument is based on knowledge of history of life on earth In other words, Why is a fly or a worm a credible model system for other organisms? Why do biologists care so much about the genome projects of non-human animals?

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Why do biologists care so much about the genome projects of non-human animals? • These model systems are credible because of our common evolutionary history • This common evolutionary origin has insured that all genomes share the same chemical composition and critical features of replication and information management. • And many different genomes share many of the same genes -- as a result of the common origin of all species on earth So studying the function of a gene in one organism may lead to an understanding of what the gene does in another organism, such as humans

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How similar is the human genome to the genome of other organisms? Some remarkable data from the mouse genome project: • The last common ancestor of mice and humans lived alongside the dinosaurs • Despite 75 million years of separate evolution, of the 30,000 genes found in the mouse genome, 99% have direct counterpoints in the human genome

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Fraction of genes in the mouse genome that are shared with each taxonomic grouping: For example, the mammalian wedge indicates

fraction of genes shared with other mammals (14%) but not with other chordates

Note large wedge of genes shared by all eukaryotic organisms (29%)

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Figure 1. (continued). Fly (F), worm (W), and yeast (Y) genes showing similarity to human disease genes. This collection of human disease genes was selected to represent a cross section of human pathophysiology and is not comprehensive. The selection criteria require that the gene is actually mutated, altered, amplified, or deleted in a human disease, as opposed to having a function deduced from experiments on model organisms or in cell culture. Results are scaled according to various levels of statistical significance, reflecting a level of confidence in either evolutionary homology or functional similarity: • White boxes: indicating no or weak similarity; • light blue boxes • purple boxes represent E • dark blue boxes: indicate the highest degree of sequence conservation. A plus sign indicates our best estimate that the corresponding Drosophila gene product is the functional equivalent of the human protein, based on degree of sequence similarity, A minus sign indicates that we were unable to identify a likely functional equivalent of the human protein.

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Other reasons why biologists care so much about the genome projects of non-human animals: Despite the commonalities unifying plants, animals, and microbes, genomic information is also key to the incredible biodiversity that exists on this planet • It is the differences in our genomes that make you and I different from a sunflower or a dragonfly • And some of the differences between individuals within a given species are genetically encoded

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Which of our genes makes us human? • The DNA sequence of our genome and that of the

chimpanzee differ by only a few % • Which of these genetic differences between the two

genomes make us human?

Some things we know about the human genome http://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer2001/4.shtml

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Want a model organism poster? Check out this link: http://www.nigms.nih.gov/Publications/modelorg_factsheet.htm