! Review. ! The Central Dogma. ! Gene Expression. ! Complementarity is the secret of life! A-T and G-C! Structure of DNA

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1 Outline : The Central Dogma & Gene Expression Lecture 5 Review!What is the secret of life?!what is a gene? Genetics & Society Honor 3215, Fall 2008 Bryan Benham The Central Dogma Gene Expression 2 Feb. 28, 1953: Two guys walk into a pub and declare they have the answer to the secret of life. Secret of Life? Complementarity is the secret of life! A-T and G-C! Structure of Needed for replication! Copies: fast and accurate Replication is at the heart of all genetic functions! : instructions (blueprints) for biological processes! Instructions need to be replicated for each process 3 4 How does this happen? Cells ~ million million ~200 different types Each makes what it needs to survive and do its job:! grow, multiple, communicate and cooperate with other cells as well as perform its particular function: e.g., carry oxygen and nutrients, flex/ contract, send messages, etc. Process and produce various materials! Water (66%), proteins*, carbohydrates, fats, minerals? 5 6

2 What is a gene? genes A gene is a section of that makes a protein (usually several 10,000 s of base pairs long) A gene is a section of s do things chromosome gene s Organic compounds made of chains of amino acids! Only 20 different amino acids s do things:! E.g., catalysts (enzymes), structure and function (cytoskeleton), cell signaling and communication, metabolism of nutrients, etc. ~ 300, ,000 proteins in humans 9 10 How do genes make proteins? The Central Dogma 11 12

3 The Central Dogma Central Dogma Catachism:! makes! makes! makes Complementarity! At each step Simplification 13 Replication 14 Video: Replication is the long-term storage medium It is too valuable to use for making things is copied when cells divide 17 "It has not escaped our notice that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material" 18

4 Complementarity allows to be copied exactly Replication Video: Replication C C T A G A G G A G A C A T A C T T G C G C C G G A T C T C C T C T G T A T G A A C G C G G C C T A G A G G A G A C A T A C T T G C G C C G G A T C T C C T C T G T A T G A A C G C G G C C T A G A G G A G A C A T A C T T G C G C C G G A T C T C C T C T G T A T G A A C G C G G (Complementarity) Central Dogma Video: Transcription Transcription Replication Transcription Polymerase Transcription Factors Promoters (Regulatory regions) Messenger (m) is a temporary copy of the information Valuable Disposable 23 24

5 is copied from 1 strand Transcription C G C T G A G G A A T A G C A C T A A G T G C G C C C C T T A T C G T G A T T C A C G C G G is copied from 1 strand Transcription C G C T G A G G A A T A G C A C T A A G T G C G C C C C T T A T C G T G A T T C A C G C G G C C T A G A G G A G A C A T A C T T G C G C C C C T A G A G G A G A C A T A C T T G C G C C G G A T C T C C T C T G T A T G A A C G C G G C C U A G A G G A G A C A U A C U U G C G C C G G A T C T C C T C T G T A T G A A C G C G G (Complementarity again) 25 C C U A G A G G A G A C A U A C U U G C G C C (m- messenger) 26 uses U in place of T uses 4 base pairs, but instead of Thymine (T) it uses Uracil (U) Because uses T, not U, the cell automatically assumes that U is the result of a C gone bad and removes all U bases from. Video: Transcription C U T 28 Central Dogma Video: Translation Transcription Replication Translation 29 30

6 is the final product of the information m Translation 31 Translation Messenger (m) Ribosome Codons Transfer Amino Acids s 32 s are made of 20 different amino acids Amino acids can be linked together (you don t have to know these diagrams) s are long chains of amino acids (a real protein would have hundreds of amino acids) s are long chains of amino acids 35 Hemoglobin chains fold into complex shapes that depend on the sequence of amino acids 36

7 An (transfer) adapter is used to convert to Complementarity is used to convert the information in into protein Amino Acid U A C t U A C U C U C C U C U G U A U G A A C G C A U G A G A G G A G A C A U A C U U G C G U G A Amino Acids t m trna is made similarly in transcription Complementarity is used to convert the information in into protein AUG is the translation start UAA UAG or UGA are stop U A C U C U C U G U A U G A A C C U C G C A U G A G A G G A G A C A U A C U U G C G U G A m U A C U C U C U G U A U G A A C C U C G C A U G A G A G G A G A C A U A C U U G C G U G A m 39 START Codons STOP 40 Video: Translation 41 42

8 Where do these events occur in the cell? Nucleus Replication! Nucleus! Not shown Transcription! Nucleus Replication m Transcription m Translation 43 Translation! Cytoplasm s! Cellular! Outside 44 A cartoon look Central Dogma Exceptions 45 viruses ( >, no ) Retroviruses ( > ) Prions ( > ) Catalytic ( >, no ) i ( >, no or ) Alternative Splicing (1 > multi-) 46 Alternative Splicing 35-59% of genes have at last one alternative splice form. Quick Review The secret of life is complementarity. is the blueprint for biological processes. Genes are a section of Genes make protein! Central Dogma 47 s do things 48

9 Question If every cell has identical, how each cell know what to do and what not to do? Gene Expression Gene Expression Different cells perform different functions, because the different cells have different genes turned on and others turned off. Gene expression: how some genes get turned on and others turned off. Turn on or Turn off means expressing or not expressing proteins (central dogma) Different cells copy different parts of the into Hemoglobin Different cells copy different parts of the into Hemoglobin Blood cell Insulin Insulin m hemoglobin Different cells copy different parts of the into Hemoglobin Insulin m Pancreas cell insulin 53 Gene Expression How genes make their products (i.e., perform their function) at the right time and in the right place. Promoters and Transcription Factors! Junk? Epigenetics! Mythelation and Histones Environment 54

10 Promoters and Transcription Factors Not all of the gets copied into Promoters are parts of a gene that identify that gene and determine when, where and how much of its product gets produced. Transcription Factors are proteins which interact with (e.g., attach to beginning of gene) to control transcription. A gene is a piece of that makes a protein Not all of the gets copied into A gene is a piece of that makes a protein Transcription factors control gene expression Transcription factor promoter promoter Some of the encodes when, where and how much of the to make. This is called the promoter Transcription factors control gene expression Transcription factor Question Where do transcription factors come from? promoter 59 60

11 Junk? Junk refers to the non-coding regions of, but research shows that junk ain t so much junk. It appears that the non-coding regions regulate some gene expression. Epigenetics Another way that gene expression is controlled is by limiting physical access to that gene. Methylation: attaching a methyl group to, at the C, which effectively blocks transcription. Histones: is packaged in loops around ball-like structures, called histones. In regions of that are tightly packaged, those genes are not accessible for transcription. Those regions that are looser are accesible. In both cases, the mechanism for transcription ( polymerase, etc.) can not reach the genes Lifestyle and environment may effect one s epigenetic code. Also, may be inherited FYI: Nova Science Now video: sciencenow/3411/02.html Sun Smoking Exercise Food Atmosphere Etc. Environment Environment The gene may not be central to the phenotype at all, or at last It shares the spotlight with other influences. Environmental, tissue and cytoplasmic factors clearly dominate the phenotypic expression processes, which may, in turn, be affected by a variety of unpredictable protein-interaction events. Paul Sliverman 65 66

12 Genotype does not equal phenotype Genes provide possibility or propensity, but do not independently determine product or expression. The exact types and amounts of protein made by our make us what we are panda.com/ Genes in some well known organisms Genes in some well known organisms /articles/12_03/yeast_screen.shtml <10!m 12 M base pairs 6,300 genes ~1 mm 97 M base pairs 19,100 genes ~1 cm 180 M base pairs 13,600 genes ~10 cm 125 M base pairs 25,500 genes Genes in some well known organisms The exact types and amounts of protein made by our make us what we are. 2,500 M base pairs ~30,00 genes 2,900 M (~3 billion) base pairs ~30,000 genes panda.com/

13 What is the central dogma? A T G C How does complementarity fit into the central dogma? Central Dogma! Replication Heliocase Polymerase (I-III)! Transcription Polymerase Transcription Factors Promoters Messenger (m)! Translation Riobsome & Codons Transfer & Amino Acids s! Not very dogmatic Summary Gene Expression! Alternative Splicing! Promoters and Transcription Factors Genes controlling genes! Epigenetics Methylation Histones! Environment Cytoplasmic Cellular Organismic External environment 74