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Retrovirus Gene expression of virus RT ENV MOBILE ELEMENTS טרנספוזונים – אלמנטים של DNA שעוברים ממקום למקום בתוך הגנום • Barbara McClintockזיהתה בשנות ה 40-שצבע גרעיני קלח תירס אינדיאני משתנים בפרק זמן קצר .היא טענה שזה נגרם כתוצאה מאלמנטים שעוברים ממקום למקום בגנום ) (transposable elementsוכתוצאה מכך משנים תהליכי התבטאות גנים המעורבים בקביעת צבע גרעין התירס. • עבודתה הוכרה כ 40-שנה לאחר מכן – 1983פרס נובל. • כיום ידוע ש 50%-מגנום התירס (2.5 ) Mbpמכיל רצפי טראנספוזונים. 1 שתי קבוצות של רצפי טראנספוזונים • • • • • • :Class Iאלמנט DNAהמכיל גן המקודד לחלבון טראנספוזאז. חלבון זה מעביר את אלמנט ה DNA-ממקום למקום בתוך הגנום. :Class IIשתי תת-משפחות :אחת שנקרת (LONG )LINE והשניה .(SORT) SINE ה - LINE -אלמנט ה DNA -מתורגם ל mRNA-ממנו מסונטזים חלבונים בניהם ) ,Reverse Transcriptase (RTואינטגראז .ה- RTמכין העתקי DNAמה ,mRNA-שמוכנסים לגנום ע"י איטגראז. - SINEכ 10%-מהגנום האנושי מכיל רצפים כאלה שניקראים רטרו-טראנספוזונים בניהם .Alu, LTRעפי"ר חסרי גנים פונקציונלים. על סמך עבודה זו Richard Dawkinsפיתח את תיאוריית the .selfish genes רטרוטרנספוזונים :רטרו , RNA -טרנספוזוניים – אלמנטיים מדלגים. Mobil DNA 2 Transposon-derived repeats סה"כ = 46%מהגנום האנושי!!! רצפי Alu pA pA • • • • • • • • • ייחודיים לפרימטים בלבד! • כ 11%-מהגנום האנושי 1.1מיליון עותקים בגנום כל 200לידות מופיע ALUחדש הופיעו מגן ה7SL- מכילים פרומוטר לpolIII- היפומתילציה מעורבת בסינדרום מלחמת המפרץ אינם מכילים את הRT- התפשטו בגנום דרך התפרצויות בעלי מנגנון בקרה שמונע השתלטות על הגנום יצירת איזה אלמנטים בגנום יכולים להיות שרידים של טרנספוזונים? 3 What are SINEs? 1. Interspersed Elements 2. 70 - 300 Bases in Length 3. Very High Copy Numbers (>100,000 Copies/Genome) 4 ALU INSERTIONS AND MUTATION Promoter alters gene expression disrupts reading frame disrupts splicing no disruption ALU INSERTIONS AND DISEASE LOCUS BRCA2 Mlvi-2 NF1 APC DISTRIBUTION de novo de novo (somatic?) SUBFAMILY Y Ya5 de novo Familial Ya5 Yb8 about 50% Ya5 Familial Y Familial one Japanese family Ya5 Yb8 familial Ya4 C1 inhibitor ACE de novo about 50% Y Ya5 Factor IX 2 x FGFR2 GK a grandparent De novo ? Ya5 Ya5 PROGINS Btk IL2RG Cholinesterase CaR Sx DISEASE Breast cancer Associated with leukemia Neurofibromatosis Hereditary desmoid disease Linked with ovarian carcinoma X-linked agammaglobulinaemia XSCID Cholinesterase deficiency Hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism Complement deficiency Linked with protection from heart disease Hemophilia Apert’s Syndrome Glycerol kinase deficiency REFERENCE Miki et al, 1996 Economou-Pachnis and Tsichlis, 1985 Wallace et al, 1991 Halling et al, 1997 Rowe et al, 1995 Lester et al, 1997 Lester et al, 1997 Muratani et al, 1991 Janicic et al, 1995 Stoppa Lyonnet et al, 1990 Cambien et al, 1992 Vidaud et al, 1993 Oldridge et al, 1997 McCabe et al, (personal comm.) UNEQUAL Alu/Alu HOMOLOGOUS RECOMBINATION 5 ALU/ALU RECOMBINATION AND GERM-LINE DISEASE LOCUS 8 x LDLR 5 x α-globin 5 x C1 inhibitor C3 HPRT DMD ADA Ins. Rec. β Antithrombin XY Lysyl hydroxylase DISTRIBUTION DISEASE REFERENCE Kindreds Hypercholesterolemia Lehrman et al, 1985, 1987 Yamakawa et al, 1989 Rudiger et al, 1991 Chae et al, 1997 Kindreds Nicholls et al, 1987 α-thalassaemia Flint et al, 1996 Harteveld et al, 1997 Ko et al, 1997 Kindreds Angioneurotic adema Stoppa-Lyonnet et al, 1990 Ariga et al, 1990 Kindred C3 deficiency Botto et al, 1992 Individual Lesch-Nyhan Marcus et al, 1993 syndrome Kindred Duchenne’s muscular Hu et al, 1991 dystrophy Individual ADA deficiency-SCID Markert et al, 1988 Individual Insulin-independent Shimada et al, 1990 diabetes Individual Thrombophilia Olds et al, 1993 Individual XX male Rouyer et al, 1987 Kindreds Ehlers-Danlos Pousi et al, 1994 syndrome ALU/ALU RECOMBINATION AND CANCER LOCUS 10 x ALL-1 DISTRIBUTION Somatic MECHANISM Alu-Alu recomb Dup. intron 1-6 DISEASE Acute myelogenous leukemia 7x BCR/Abl Somatic X-Alu recomb. CML All-1/AF9 Somatic Alu-Alu translocation 2x BRCA1 Somatic & A kindred 2x MLH1 2 kindreds Alu-Alu recomb (del exon 17; del. Promoter) Alu-Alu recomb. (del exon 16) (exons 13-16) Acute myelogenous leukemia Breast cancer TRE RB EWS 6 REFERENCE Strout et al, 1998 So et al, 1997; Schichman et al, 1994 Jeffs et al, 1998 Chen et al, 1989 de Klein et al, 1986 Super et al, 1997 Somatic Ewing's sarcoma Puget et al, 1997 Swensen et al, 1997 Nystrom-Lahti et al, 1995 Mauillon et al, 1996 Onno et al, 1992 Common Association with glioma Protective against Ewing Sarcoma? Rothberg et al, 1997 Zucman-Rossi et al, 1997 Interchromosomal Alu-Alu recomb Alu-Alu recomb. (799 bp del.) Subset of Africans Alu-Alu recomb. (del 2 kb) HNPCC 7 הטרנספוזונים כנראה גרמו לשינויים,DNA-למוטציות ב בתהליך התבטאות הגנים ובכך .גרמו לשונות גנטית Identification of alternatively spliced Alu exon I II III IV Alu C9, NT_008541 AF010316 AF217965 AF217972 BE614743 BE616884 AI972259 5.2% of the alternatively spliced exons (1182) has a significant hit to an Alu sequence (E < 10-10). But, none of the constitutively spliced exons (4152) has a significant hit to an Alu sequence. That means, that Alu-containing exons are alternatively spliced. Sorek et al., 2002 Alu are Retrotransposons. Alu elements Alu sequences both comprise more than 11% of the genome and have reached a copy number of about 1.4 million. Alu elements are short interspersed elements (SINEs), typically 300 nucleotides long, containing two cassettes separated by a polyA tail. Alu elements are unique to primates 8 pA pA All introns of >1000 bp contain at least 1 Alu Exsonization of Alu elements Exon Exon 1 Alu Exon 2 splicing Alport Sly Exon 1 Exon 1 OAT Exon 2 Isoform A A Exon 2 Isoform B מהם התהליכים שעיצבו את הגנום האנושי Origin of life Who’s first DNA, RNA or Protein? What is the advantage of having introns? The Origin of Life – a Fact and an Assumption • Unity of life – all extant living organisms are constructed of the same materials, and function according to the same principles . כל היצורים מורכבים מאותן מולקולות ופועלים על סמך אותם .עקרונות • All organisms are descendants of a single ancestral form of life. האם לכל האורגנזמים אב קדמון משותף ?אחד De duve ,chap1 9 Two Big Questions 1. What is the manner in which the ancestor emerged from materials available then? Can we reconstruct it? האם,כיצד האב הקדמון נוצר המולקולות שהיו זמינות ?אנו מסוגלים לשחזר את התהליך 2. How did all extant living organisms evolve from the common ancestor? ?כיצד כל האורגנזמים החיים התפתחו מאב קדמון אחד Are we alone? A. Yes B. No How do you think life originated on earth? Extraterrestrial aliens brought it Came with meteors from other planets Some superhuman powers created it Chemical from primordial soup combined to make life None of the above 10 .A .B .C .D .E המפץ הגדול 11 History of Life Stromatolites Early prokaryotes 12 Cyanobacteria fossils Possible Sources of Life’s Origin Which came first? A. DNA B. RNA C. Protein D. Carbohydrates E. Lipids PROTEIN Æ (Catalytic and Information) Structural) 13 RNA (Information Æ and catalytic) DNA (Genetic Abiotic RNA Replication Primitive RNA and Proteins Which of the following is/are testable hypothesis about origin of life on earth? Extraterrestrial aliens brought it Came with meteors from other planets Some superhuman powers created it Chemical from primordial soup combined to make life None of the above 14 .A .B .C .D .E The Five Kingdom System Domain Systems 15 16 17 18 19 20 21 Origin of Life: Another idea Biogenic-looking features in ALH84001 Martian meteorite http://ares.jsc.nasa.gov/astrobiology/biomarkers/images.html Conditions on the Early Earth A hot reducing environment High temperatures H2O, CO2, N2 H2S, CH4, NH3, H2 No O2 Text pg. 451 22 • • • • • • Subsequent modifications of the atmosphere have produced representatives or precursors of all four organic macromolecular classes. Including the molecules below: Miller Experiment In 1950, a student, Stanley Miller, designed an experiment in which he discharged an electric spark into a mixture thought to resemble the primordial composition of the atmosphere. From the water receptacle, designed to model an ancient ocean, Miller recovered some amino acids. The History of Life on Earth When did life arise on Earth? • The Earth is thought to be approximately 4.6 billion years old, but life is believed to have occurred approximately 4 billion years ago (bya) •How did life begin??? 23 The Origin of Life: Early Ideas Spontaneous Generation • idea popular in the 1600-1700’s – living things come from the nonliving – evidence: beetles and other insect larvae arise from cow – dung; frogs emerge from mud In 1688, the Italian Francisco Redi In 1668, Francesco Redi, an Italian physician, did an experiment with flies and wide-mouth jars. He demonstrated that meat that was covered did not produce maggots • This may have been the first true scientific experiment… • Francesco Redi experiment with flies and wide-mouth jars The Origin of Life generation Spontaneous Mid-1800s—disproved by Louis Pasteur and John • Tyndall no growth Broth in flask is boiled to kill preexisting microorganisms. 24 Condensing water collects as the broth cools, sealing the mouth of the flask. growth If neck is later broken off, outside air can carry microorganisms into broth. Other Ideas: Life from a Biblical Creation? Christian Creationism states that the world, including all life, was created about 6,000 years ago in six literal days by a God. …But how does one accurately and fairly test for this?... What’s the observation, hypothesis, test…? This idea does not really fit into the confines of a Science course. Like the study of French Impressionist painters, Religion is not part of, nor adequately covered in, a Science course. Origin of Life: Another idea Biogenic-looking features in ALH84001 Martian meteorite http://ares.jsc.nasa.gov/astrobiology/biomarkers/images.html 25 Extra-terrestrial Origins In 1969, a meteorite (left-over bits from the origin of the solar system) landed near Allende, Mexico. The Allende Meteorite (and others of its sort) have been analyzed and found to contain amino acids, the building blocks of proteins. This idea of panspermia hypothesized that life originated out in space and came to earth inside a meteorite. The amino acids recovered from meteorites are in a group known as exotics: they do not occur in the chemical systems of living things. The ET theory is now discounted by most scientists, although the August 1996 discovery of the Martian meteorite and its possible fossils have revived thought of life elsewhere in the Solar System. Anyway….This only moves the problem to elsewhere! The Latest on Extra-terrestrial Origins… The Raelians Raelians believe that humanity • was created from the DNA of superior alien scientists Follow the teachings of a former • French magazine sportswriter and wannabe race-car driver Claude Vorilhon, 56. He took the name "Rael" after he claimed a close encounter of the third kind…. Origin of Life: Current Theory Chemical Evolution .....The idea that long ago complex collections of chemicals formed the first cells. Life began in the oceans 4 bya from simple chemicals joining together in a “primordial soup” Complex chemicals evolved into living cells 26 • • • • What were the conditions like on Earth when life arose? • Up to about 4 bya, asteroid impacts and volcanic eruptions resulted in the release of various gases that began to form an atmosphere • It consisted mainly of CO2, with some nitrogen, water vapor and sulfur gases; hydrogen quickly escaped into space • CO2 in the atmosphere trapped solar radiation, making the Earth’s surface rather warm • Earth was cool enough to form a crust, and water vapor condensed to form oceans • Oceans in turn helped to dissolve CO2 from the atmosphere and deposit it into carbonate rocks on the seafloor What were the conditions like on Earth when life arose? • Organic molecules were undoubtedly being formed on the Earth’s surface • Lightening and ultraviolet radiation from the Sun acted on the atmosphere to forms small traces of many different gases, including ammonia (NH3), methane (CH4), carbon monoxide (CO) and ethane • Also, cyanide (HCN) probably formed easily in the upper atmosphere, from solar radiation and then dissolved in raindrops The Origin of Life Early Speculations What are the possible scenarios? • When ocean tidal pool evaporates – Salts get highly concentrated • Could have happened in ancient oceans – Concentrating aminos, may allow protein • to form 27 The Origin of Life Early Speculations Phospholipids arrange themselves into bubbles • Chemicals could be concentrated in bubbles (might – contain protein, etc.) These bubbles would persist aided by natural selection – If they burst, spew contents into air where other – reactions occur Over hundreds of millions of years, similar processes – could have filled oceans with proteins, carbohydrates, phospholipids, nucleotides The Origin of Life Early Speculations Phospholipids arrange themselves into • bubbles Eventually they reach a level of – complexity Called protocells (not living) • Still can’t reproduce, no DNA • The Origin of Life Early Speculations Is DNA essential? • Scripps Institute, 1993 found small molecules – of synthetic RNA that within an hour began making copies of itself & the copies made more copies Then copies began to change - evolve- – acquiring new chemical characteristics, but not alive 28 The Origin of Life Early Speculations Is DNA essential? • Protocells might qualify as the first cells if they have – RNA that: Can make copies of itself & evolve • Could synthesize enzymes capable of breaking down • other organic compounds Could synthesize enzymes capable of building and • maintaining cell membranes Later DNA could have evolved as method of conveniently – & safely Storing vital chemical info contained in cell RNA • The Origin of Life Early Speculations First Cell Types Heterotrophic cells • Incapable of producing their own food – Autotrophs • Can produce chemicals to store energy – Chemoautotrophs • Store energy found in certain inorganic chemicals – 29 First Cell Types Most organisms found free oxygen intolerable • In oceans – Organisms that built simple and complex organic • compounds Removed CO2 from the atmosphere • More advanced autotrophs removed most of the rest & • replaced it with oxygen The excess oxygen changed forever chemical nature of • atmosphere to today’s Further Evolution of First Cells First cells, prokaryotes, were always simple in • structure 2 - 1.5 billion years ago • A new cell appeared – eukaryotes – Had membranes to isolate certain chemical – reactions Cellular life then evolved into what we know • today Archaea & Bacteria Domains Directly related to oldest organisms on earth • Have had lots of time to evolve & differentiate – Thrive nearly everywhere • Depths of oceans & Earth, all surfaces – 30 Multicellular organisms A. Advantages of multicellularity • B. Challenges of multicellularity • C. The first multicellular organisms • 1. Plants—primitive marine algae 2. Animals—marine invertebrates • • D. The transition to land 1. Advantages of terrestrial living 2. Challenges of terrestrial living • • • III. Multicellular organisms The transition to land • The evolution of land plants • a. The first land plants 1) Mosses and ferns 2) Continued water dependency • • • b. Conifers—the invasion of dry habitats • c. Flowering plants • 1) The dominant plant form today 2) Pollination by insects • • • III. Multicellular organisms D. The transition to land • The evolution of terrestrial animals • a. Arthropods • b. Lobefin fish to amphibians • c. Amphibians to reptiles • 1) The age of the dinosaurs 2) Reptiles and maintenance of body temperature • • d. Birds 1) Insulating feathers retain body heat 2) Evolution of feathers for flight 31 • • • III. Multicellular organisms The evolution of terrestrial animals e. Mammals 1) Insulating hair retains body heat • 2) Live births and mammary glands • • IV. Human evolution A. Primate evolution 1. Grasping hands—precision grip and power grip • 2. Binocular and color vision with overlapping fields of view • 3. Large brain—allows fairly complex social systems • H.habilis H.sapiens Homo ergaster H. heidelbergensis Australopithecus afarensis H. neanderthalensis H. erectus A. robustus Ardipithecus ramidus A. africanus A. boisei 32 • • IV. Human evolution Hominid evolution • 1. The evolution of dryopithecines—between • 20 and 30 million years ago 2. Australopithecines—the first true hominids • a. Appeared 4 million years ago as evidenced by • fossils b. Walked upright • c. Large brains • IV. Human evolution 3. Homo habilis—2 million years ago • a. Larger body and brain • b. Ability to make crude stone and bone tools • 4. Homo erectus—1.8 million years ago • a. Face of modern human b. More socially advanced c. Sophisticated stone tools aided in hunting d. Used fire • • • • IV. Human evolution 5. Homo sapiens—200,000 years ago a. Neanderthals evolved 100,000 years ago • • 1) Similar to humans–muscular, fully erect, • dexterous, large brains 2) Developed ritualistic burial ceremonies • b. Cro-Magnons evolved 90,000 years ago 1) Direct descendants of modern humans • 2) Were artistic and made precision tools • 33 • Panspermia Possible Steps in the Origin of Life Protobionts and Liposomes 34 The Origin of Life The possible origin of organic molecules a. 1953—the Stanley Miller experiment • What is the simplest living cell that one can imagine? A universal minimal cell must contain the following:: • Cell membrane • Cytoplasm • DNA and RNA • Proteins • Enzymes • Ribozymes The Origin of Life Early Speculations More circumstantial evidence • accumulated Astronomers found simple organic – compounds in meteorites They were convinced that Earth’s initial – atmosphere could not have matched OparinHaldane’s model 35 The Origin of Life Early Speculations More circumstantial evidence • Fossils of ancient bacteria (3.5 billion years old) were – found in Australia Suggested life may have evolved rapidly in less than a – billion years The First Cells Age of microbes—3.5 billion years ago 1. The earliest living cells—anaerobic prokaryotes • 2. Photosynthetic bacteria and the evolution of an oxygen-rich environment • 3. Development of aerobic metabolism • II. The first cells The rise of eukaryotes—about • 1.4 billion years ago 1. Endosymbiotic hypothesis • 2. The origin of the nucleus • 36 • 1. Anaerobic, predatory prokaryotic cell engulfs an aerobic bacterium. aerobic bacterium 2. Descendants of engulfed bacterium evolve into mitochondria. 3. Mitochondria-containing cell engulfs a photosynthetic bacterium. 4. Descendants of photosynthetic bacterium evolve into chloroplasts. תא בקטריאלי מול תא הומאני 37 Searching for the Origin Domain Bacteria Domain Archaea Domain Eukarya Common Ancestor 1. Anaerobic, predatory prokaryotic cell engulfs an aerobic bacterium. aerobic bacterium 2. Descendants of engulfed bacterium evolve into mitochondria. 3. Mitochondria-containing cell engulfs a photosynthetic bacterium. 4. Descendants of photosynthetic bacterium evolve into chloroplasts. 38 .(כל האורגנזמים החיים בנויים באותו אופן – תא )יצור חד או רב תאי כל התאים מפעילים את אותה תוכנית – תהליך התבטאות הגנים RT Human vs. Human • A variation every 1000 nucleotides. • 90% of human variation is within African populations. • There are enough humans, and the mutation rate is high enough, that on average each base is mutated several times in each generation. • Humans each carry hundreds of bad mutations. Most are recessive, only show up with inbreeding. 39 Human vs. Chimpanzee • A difference every 100 bases. • A new transposon every 50,000 bases • Two chromosome in one species fused compared to the other. Human vs. Mouse אב קדמון משותף 110 - 70 לפני .מליון שנה In general 40% of bases have changed. • In functional regions only 15% of bases have • changed. Looking for conserved regions between human • and mouse helps identify functional parts of human genome. MouseMouse-human synteny. synteny. Human chromosomes can be cut into ~150 pieces, then shuffled into a reasonable approximation of the mouse genome. 40 There are genegene-dense (urban centers) and genegene-poor (deserts) chromosomes From 23 genes per million base pairs on chromosome 19 (3% (3%)) to only 5 genes per ). million base pairs on chromosome 13 (0.7% (0.7%). 959 cells 1,031 cells ~108 cells 19,000 genes 13,600 genes K-value paradox: Complexity does not correlate with chromosome number. Homo sapiens 46 41 Lysandra atlantica 250 Ophioglossum reticulatum 1260 C-value paradox: Complexity does not correlate with genome size. 3.4 × 10 9 bp Homo sapiens 6.7 × 1011 bp Amoeba dubia N-value paradox: Complexity does not correlate with gene number. ~31,000 genes ~26,000 genes ~50,000 genes 42 Building a Body from DNA • 3 billion bases of human DNA contain roughly 30,000 genes. . גנים30,000- בליון בסיסים מכילים כ3 • The products of the genes are the parts that make up a cell. .תוצרי הגנים יוצרים את התא • These genes are turned on and off in a very intricate fashion to form and maintain a human body. הפעלת הגנים הינו תהליך מורכב שבונה ומתחזק את .הגוף האנושי • Some genes regulate other genes. חלק מהגנים מבצעים .רגולציה לגנים אחרים How DNA is Used by the Cell Promoter Tells Where to Begin Different promoters activate different genes in different parts of the body. תוצרי.פרומוטורים שונים מאקטבים גנים המתבטאים ברמות שונות ברקמות גופנו כך,הגנים – החלבונים – יכולים להיות מעורבים בכמה מעגלים שונים בתוך התא .שתהיה להם יכולת לשלוט במספר תהליכים תוך תאיים ולתאם ביניהם 43 תהליכים שגרמו להתהוות הגנום האנושי תהליכי דופליקציה שיחררו את הסט השני להתמחות בפונקציות חדשות מוטציות גרמו לתהליך שיוצר שונות גנים פרוקריוטים פלשו לגנום האוקריוטי200-כ והמערכת האימוניתDNA תיקון,שיפור של מערכות כמו הפעלות גנים Retrovirus Gene expression of virus RT ENV הכמיה של ראקצית splicing-ה lariat שלבית-ראקציה דו המורכבת משתי ראקציות אסטרפיקציה עוקבות-טראנס The Exon Theory of Genes • Theory of origin of protein function • LUCA and before: – – – – – – – – 44 many linear small proto-chromosomes introns provide recombination opportunity short stretches of exon RNA coding for proteins 15-20 amino acids long selection for function in these short proteins precursors of functional domains exon shuffling gives functional diversity linking of functioning proteins The Human Genome ?בשביל מה אנחנו זקוקים לאינטרונים 2.91 billion base pair 26,000-38,000 genes גנים50-100,000 הערכה ראשונית דיברה על 1.1% of the genome is exons 24% introns 75% intergenic (no-genes) Average size of a gene is 27,894 bases Contain an average of 7-7.8 exons The gene with most exons is Titin containing 234 exons האם האינטרונים הופיעו לאחר שהגנום היה קיים (introns first or invaded) ?או במהלך התהוותו Introns Early, Introns Late Two views of Life 45 • Introns Early • Introns Late • Eukaryotic nuclear genome original • Prokaryotic genome derived • Exons old • Exon shuffling old form of gene increase • Prokaryotic genome original • Eukaryotic nuclear genome derived • Exons young • Exon shuffling recent form of gene increase The network of RNA interactions in the spliceosome snRNP אבולוציה של ה 46 The route of intron invasion of new chromosomal sites מהגנים40% Alternative splicing סוגים שונים של חלבונים הנוצרים מאותו חלבון נקראים איזופורמים Why do we even have introns? • Regulatory role? – Control gene activity – Regulate movement of mRNA from nucleus to cytoplasm Alternative splicing • Evolution of new proteins-EXON SHUFFLING – Homologous recombination – Change particular domains/exons – Get Recombination of different exons, not the whole gene 47 The Path to DNA/proteins System stability Abiotic ( )דומםworld catalytic RNARNA-World DNA /proteins replication flexibility Who Was First ? Proteins or Nucleic Acids? Proteins Nucleic acids Both It is easier to polymerize proteins than nucleotides special conditions in the soup enabled replication without proteins relation from the start: (A) proteins-nucleotids (B) Amino acids codons RNA World Model: Evolution from RNA to DNA Emerging of RNA as an outcome of 2. Catalytic polymerizationRNA self function ? replicating without enzymes RNA - proteins 1. How ? system Who/Which? DNA-RNA-proteins 3. The path? system mechanism to path ? 48 5S rRNA proteins A-site tRNA 23S rRNA peptidyl transfer reaction: P-site tRNA הבדלים בדפוסי התבטאות חלבונים בין מוח של אדם לשימפנזה Chimpanzee Human מהם התהליכים שעיצבו את הגנום האנושי Origin of life Who’s first DNA, RNA or Protein? What is the advantage of having introns? 49