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Biology 205 Spring 2008 Week 1 Lecture 3 Reading assignment for Monday’s Lecture: In Alberts: Chapter 2 pp. 50-52, 55-56 Panel 2-1 (chemical bonds) Panel 2-2 (water) Panel 2-5 (amino acids) Chapter 4 pp 119 -143

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One goal of the genome projects is to determine the complete genome sequence for a variety of orgamisms What is meant by the DNA sequence?

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What is meant by the DNA sequence? The complete order (linear arrangment) of monomer units in the DNA polymers that make up the genome Some things we know so far about the human genome http://www.ornl.gov/sci/techresources/Human_Genome/publicat/primer2001/4.shtml

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The genetic information contained in DNA is • one dimensional: encoded along the length of a

molecule • digital: because the basic information unit (the

nucleotide or base) can exist in only one of four discrete states abbreviated: G, A, T, C

>gi|17488858|ref|XM_010627.4| Homo sapiens SRY (sex determining region Y chromosome)

Shorthand abbreviation of part of the DNA sequence of the SRY gene GGCATGTGAGCGGGAAGCCTAGGCTGCCAGCCGCGAGGACCGCACGGAGGAGGAGCAGGAGCGCGGAGCCGCGAGCCCCGAGCCCCGAGCCCGGCGCCTGGCTGAGTAGATGTCCATGAGGAGCCCCATCTCTGCCCAGCTGGCCCTGGATGGCGTTGGCACCATGGTGAACTGCACCATCAAGTCAGAGGAGAAGAAAGAGCCTTGCCACGAGGCCCCCCAGGGCTCAGCCACTGCCGCTGAACCTCAGCCTGGAGACCCAGCCCGGGCCTCCCAGGATAGTGCTGACCCCCAAGCTCCAGCCCAGGGGAATTTCAGGGGCTCCTGGGACTGTAGCTCTCCAGAGGGTAATGGGTCCCCAGAACCCAAGAGACCAGGAGTGTCGGAGGCTGCCTCTGGAAGCCAGGAGAAGCTGGACTTCAACCGAAATTTGAAAGAAGTGGTGCCAGCCATAGAGAAGCTGTTGTCCAGTGACTGGAAGGAGAGGTTTCTAGGAAGGAACTCTATGGAAGCCAAAGATGTCAAAGGGACCCAAGAGAGCCTAGCAGAGAAGGAGCTCCAGCTTCTGGTCATGATTCACCAGCTGTCCACCCTGCGGGACCAGCTCCTGACAGCCCACTCGGAGCAGAAGAACATGGCTGCCATGCTGTTTGAGAAGCAGCAGCAGCAGATGGAGCTTGCCCGGCAGCAGCAGGAGCAGATTGCAAAGCAGCAGCAGCAGCTGATTCAGCAGCAGCATAAGATCAACCTCCTTCAGCAGCAGATCCAGCAGGTTAACATGCCTTATGTCATGATCCCAGCCTTCCCCCCAAGCCACCAACCTCTGCCTGTCACCCCTGACTCCCAGCTGGCCTTACCCATTCAGCCCATTCCCTGCAAACCAGTGGAGTATCCGCTGCAGCTGCTGCACAGCCCCCCTGCCCCAGTGGTGAAGAGGCCTGGGGCCATGGCCACCCACCACCCCCTGCAGGAGCCCTCCCAGCCCCTGAACCTCACAGCCAAGCCCAAGGCCCCCGAGCTGCCCAACACCTCCAGCTCCCCAAGCCTGAAGATGAGCAGCTGTGTGCCCCGCCCCCCCAGCCATGGAGGCCCCACGCGGGACCTGCAGTCCAGCCCCCCGAGCCTGCCTCTGGGCTTCCTTGGTGAAGGGGACGCTGTCACCAAAGCCATCCAGGATGCTCGGCAGCTGC…….. ………………………….. etc, etc, etc,

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TTACCCATTCAGCCCATTCCCTGCAAACCAGTGGAGTATCCGCTGCAGCTGCTGCAC AGCCCCCCTGCCCCAGTGGTGAAGAGGCCTGGGGCCATGGCCACCCACCACCCCCTGCAGGAGCCCTCCCAGCCCCTGAACCTCACAGCCAAGCCCAAGGCCCCCGAGCTGCCCAACACCTCCAGCTCCCCAAGCCTGAAGATGAGCAGCTGTGTGCCCCGCCCCCCCAGCCATGGAGGCCCCACGCGGGACCTGCAGTCCAGCCCCCCGAGCCTGCCTCTGGGCTTCCTTGGTGAAGGGGACGCTGTCACCAAAGCCATCCAGGATGCTCGGCAGCTGC…….. ………………………….. etc, etc, etc,

THis is a shorthand for TTACCCATTCA GCCCATTCCCTGC AAACCAGTGGAGTATCCGCTGCAGCTG AATGGGTAAGTCGGGTAAGGGACGTTTGGTCACCTCATAGGCGACGTCGAC ETC. ETC. ETC.

What does this symbolism mean chemically? What does this symbolism mean biologically?

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What does this symbolism mean chemically?

Lets take this molecule apart:

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DNA is a type of macromolecule macromolecule: giant molecule Most macromolecules polymers What’s a polymer?

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polymer: long molecule consisting of many similar (or identical) building blocks linked by covalent bonds monomer: the repeating unit of a polymer

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DNA contains two polymers wound around each other:

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DNA is a polymer of four different monomer units Each monomer unit contains: 1. a carbohydrate: deoxyribose (in ring form) 2. a phosphate attached to the deoxyribose 3. one of four different nitrogenous bases The nitrogenous bases are called A = adenine G = guanine T = thymine C = cytosine

P

ribosesugar

phosphate

base

Each monomer unit has this generic structure.The monomer units differ in the structure of the base

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P

ribosesugar

phosphate

base

Each monomer unit has this generic structure.The monomer units differ in the structure of the base

monomer units are called: nucleotides or bases When paired (via hydrogen bonds) in double-stranded DNA - base pairs or nucleotide pairs

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Some impressive facts about DNA polymers: • A single copy of the human genome contains 3 X 109

base pairs • Each single copy of the human genome is divided into

23 polymers of DNA (representing the 23 chromosomes present in a single copy of genome)

• So each chromosome consists of ONE continuous polymer of double-stranded DNA

• If all chromosomes were equal in size then the average length of a DNA molecule (double helical polymer) would be 130 million (3 X109/23) base pairs

• The chromosomes vary in size though and the so the actual length of the DNA molecules vary in size.

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Cartoon of the chromosomes of the human genome Note scale on vertical arrow= 50 X 106 base pairs Base pairs = nucleotide pairs = bases = monomer units The SRY (human sex-determining) gene is located at the upper tip of the Y chromosome.

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TTACCCATTCA GCCCATTCCCTGC AAACCAGTGGAGTATCCGCTGCAGCTG AATGGGTAAGTCGGGTAAGGGACGTTTGGTCACCTCATAGGCGACGTCGAC

In terms of a digital code a T in the first position (top strand) is differentiated from G, C and A by a different H-bonding surface or capacity – we will explore this issue in detail when we examine replication, transcription and translation What does this symbolism mean biologically? The chemical structure of DNA must explain • How genetic information is stored in the

molecule • How the replication of genetic information is

accomplished • How the stored information is expressed in

the living organism • How changes in the stored information come

about: how mutations occur

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permanent chemical carrier of genetic instructions short-term copy DNA mRNA PROTEIN genetic information genetic information ↓ is copied over is converted to a different or transcribed chemical form or translated ↓ from one chemical language ↓ to another ↓ Control of Biological of processes/Specification of an organism Basic themes in Molecular biology • DNA is the permanent chemical record of the genetic

instructions for an organism • genetic information is stored in the linear arrangement or

sequence of the nucleotide residues (bases) that constitute the DNA chain

• The information stored in DNA is converted by the cell into a different chemical form: proteins (and RNA)

• Proteins directly or indirectly control most aspects of the development and functioning of an organism

DNA --- (triplet genetic code) -- proteins proteins ----- ? ------- organism

rRNAs, tRNAs miRNAs siRNAs and others

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The information associated with living organisms exists at three levels of complexity: The first level is genetic information encoded in DNA • one dimensional: encoded along the length of a molecule • digital: because the basic information unit (the nucleotide) can

exist in only one of four discrete states The second level of biological information is encoded in proteins • Proteins contain 3-dimensional information which is specified

by the one-dimensional information in the DNA polymer • Proteins operate as molecular machines that carry out the

functions of life by virtue of their shape and chemistry The broad third level of biological information is a biological system: • A biological system is any complex interacting network of

molecules or groups of cells that function in a coordinated manner (such as the nervous system)

• There are several layers of biological systems: organ, organism, community of organisms

• This information is four dimensional because it changes over time and thus includes the three dimensions of space and one dimension of time

• One of the more complex examples of the third level of biological information is the human brain

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Functional categories of proteins • enzymes: the biological catalysts (almost all reactions that occur in

living organisms are catalyzed by enzymes) • transport: hemoglobin binds and transports O2 and CO2 in red blood

cells • nutrient and storage: seed proteins of grains, ovalbumin (major

protein of egg white); casein (major protein of milk) • structural proteins: provide mechanical support and shape to cells

(include keratin -- hair protein) • contractile and motile proteins: assemblies of proteins that can do

mechanical work: contraction of muscles, movement of chromosomes at mitosis

• regulatory proteins: polypeptide hormones and other regulators of cellular or physiological activities (including the decoding of the information in DNA)

• defense proteins: immunoglobulins (antibodies) are one class of proteins that function in the immune system; blood clotting proteins (fibrinogen and thrombin)

• other proteins: functions are exotic and not easily categorized (antifreeze proteins found in Antarctic fish)

Recall the SRY gene which was mentioned in passing last week: this gene codes for a developmental regulatory protein: • it orchestrates the development of a testes (rather

than an ovary) from the developing gonad • the SRY protein controls the "expression" of specific

genes associated with the sexual identity of the gonad (testes or ovary)

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>gi|17488858|ref|XM_010627.4| Homo sapiens SRY (sex determining region Y chromosome) Shorthand abbreviation of part of the DNA sequence of the SRY gene GGCATGTGAGCGGGAAGCCTAGGCTGCCAGCCGCGAGGACCGCACGGAGGAGGAGCAGGAGCGCGGAGCCGCGAGCCCCGAGCCCCGAGCCCGGCGCCTGGCTGAGTAGATGTCCATGAGGAGCCCCATCTCTGCCCAGCTGGCCCTGGATGGCGTTGGCACCATGGTGAACTGCACCATCAAGTCAGAGGAGAAGAAAGAGCCTTGCCACGAGGCCCCCCAGGGCTCAGCCACTGCCGCTGAACCTCAGCCTGGAGACCCAGCCCGGGCCTCCCAGGAT AGTGCTGACCCCCAAGCTCCAGCCCAGGGGAATTTCAGGGGCTCCTGGGACTGTAGCTCTCCAGAGGGTAATGGGTCCCCAGAACCCAAGAGACCAGGAGTGTCGGAGGCTGCCTCTGGAAGCCAGGAGAAGCTGGACTTCAACCGAAATTTGAAAGAAGTGGTGCCAGCCATAGAGAAGCTGTTGTCCAGTGACTGGAAGGAGAGGTTTCTAGGAAGGAACTCTATGGAAGCCAAAGATGTCAAAGGGACCCAAGAGAGCCTAGCAGAGAAGGAGCTCCAGCTTCTGGTCATGATTCACCAGCTGTCCACCCTGCGGGACCAGCTCCTGACAGCC

Proteins are polymers of amino acids http://www.clunet.edu/BioDev/omm/aa/aa.htm Shorthand abbreviation of the protein sequence coded for by the SRY gene >gi|17384045|emb|CAD13147.1| sex determining region Y [Homo sapiens] MQSYASAMLSVFNSDDYSPAVQENIPALRRSSSFLCTESCNSKYQCETGENSKGNVQDGVKRPMNAFIVWSRDQRRKMALENPRMRNSEISKQLGYQWKMLTEAEKWPFFQEAQKLQAMHREKYPNYKYRPRRKAKMLPKNCSLLPADPASVLCSEVQLDNRLYRDDCTKATHSRMEHQLGHLPPINAASSPQQRDRY

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Protein is polymer of amino acids connected by peptide bonds -- also called polypeptides

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Scale: how long are these protein polymers? Range from relatively short to very long: most polypeptides contain fewer than 2000 amino acids the average yeast polypeptide is 466 amino acids long insulin is only 51 amino acids long Apolipoprotein B (human): 4,536 aa long (involved in cholesterol transport in the blood)