1
Retrovirus
Gene expression of virus
RT
ENV
MOBILE ELEMENTS
DNAשלאלמנטים–טרנספוזוניםהגנוםבתוךלמקוםממקוםשעוברים
•Barbara McClintockזיהתהתירסקלחגרעינישצבע40-הבשנות
היא. קצרזמןבפרקמשתניםאינדיאנימאלמנטיםכתוצאהנגרםשזהטענה
בגנוםלמקוםממקוםשעוברים(transposable elements)וכתוצאה
גניםהתבטאותתהליכימשניםמכך.התירסגרעיןצבעבקביעתהמעורבים
מכןלאחרשנה40-כהוכרהעבודתה•.נובלפרס1983–
2.5)התירסמגנום50%-שידועכיום•Mbp) טראנספוזוניםרצפימכיל.
2
טראנספוזוניםשתי קבוצות של רצפי •Class I :אלמנטDNAטראנספוזאזלחלבוןהמקודדגןהמכיל .
. הגנוםבתוךלמקוםממקוםDNA-האלמנטאתמעבירזהחלבון•Class II :אחת שנקרת : משפחות-שתי תתLINE )(LONG
. SINE ) (SORT והשניהמסונטזיםממנוmRNA-למתורגםDNA- האלמנט - LINE-ה•
-ה. ואינטגראז, Reverse Transcriptase (RT)בניהםחלבוניםRTהעתקימכיןDNAמה-mRNA ,י "עלגנוםשמוכנסים
. איטגראז•SINE - שניקראיםכאלהרצפיםמכילהאנושימהגנום%10-כ
חסרי גנים ר"עפי .Alu, LTRבניהםטראנספוזונים-רטרו.פונקציונלים
theתיאורייתאתפיתחRichard Dawkinsזועבודהסמךעל•selfish genes.
אלמנטיים – טרנספוזוניים , RNA -רטרו: רטרוטרנספוזונים•.מדלגים
Mobil DNA
3
Transposon-derived repeats
!!! מהגנום האנושי46%= כ "סה
Aluרצפימהגנום האנושי11%-כ•מיליון עותקים בגנום1.1•חדשALUלידות מופיע 200כל •7SL-המגןהופיעו•polIII-ל פרומוטר מכילים• בסינדרום מעורבת היפומתילציה•
המפרץ מלחמתRT-האתמכיליםאינם•התפרצויותדרךגנוםבהתפשטו•השתלטותשמונעבקרהמנגנוןבעלי•
הגנוםעליצירת •
?טרנספוזוניםאיזה אלמנטים בגנום יכולים להיות שרידים של
pApA
!ייחודיים לפרימטים בלבד
4
What are SINEs?
1.1. Interspersed ElementsInterspersed Elements
2.2. 70 70 -- 300 Bases in Length 300 Bases in Length
3.3. Very High Copy NumbersVery High Copy Numbers(>100,000 Copies/Genome)(>100,000 Copies/Genome)
5
Promoter
disrupts reading frame
disrupts splicing
no disruption
ALU INSERTIONS AND MUTATION
alters gene expression
ALU INSERTIONS AND DISEASE
LOCUS DISTRIBUTION SUBFAMILY DISEASE REFERENCEBRCA2 de novo Y Breast cancer Miki et al, 1996Mlvi-2 de novo (somatic?) Ya5 Associated with
leukemiaEconomou-Pachnis andTsichlis, 1985
NF1 de novo Ya5 Neurofibromatosis Wallace et al, 1991APC Familial Yb8 Hereditary desmoid
diseaseHalling et al, 1997
PROGINS about 50% Ya5 Linked with ovariancarcinoma
Rowe et al, 1995
Btk Familial Y X-linkedagammaglobulinaemia
Lester et al, 1997
IL2RG Familial Ya5 XSCID Lester et al, 1997Cholinesterase one Japanese family Yb8 Cholinesterase
deficiencyMuratani et al, 1991
CaR familial Ya4 Hypocalciurichypercalcemia and
neonatal severehyperparathyroidism
Janicic et al, 1995
C1 inhibitor de novo Y Complement deficiency Stoppa Lyonnet et al, 1990ACE about 50% Ya5 Linked with protection
from heart diseaseCambien et al, 1992
Factor IX a grandparent Ya5 Hemophilia Vidaud et al, 19932 x FGFR2 De novo Ya5 Apert’s Syndrome Oldridge et al, 1997GK ? Sx Glycerol kinase
deficiencyMcCabe et al, (personalcomm.)
UNEQUAL Alu/Alu HOMOLOGOUS RECOMBINATION
6
ALU/ALU RECOMBINATION AND GERM-LINE DISEASE
LOCUS DISTRIBUTION DISEASE REFERENCE 8 x LDLR
Kindreds Hypercholesterolemia Lehrman et al, 1985, 1987 Yamakawa et al, 1989 Rudiger et al, 1991 Chae et al, 1997
5 x α-globin Kindreds α-thalassaemia Nicholls et al, 1987 Flint et al, 1996 Harteveld et al, 1997 Ko et al, 1997
5 x C1 inhibitor
Kindreds Angioneurotic adema Stoppa-Lyonnet et al, 1990 Ariga et al, 1990
C3 Kindred C3 deficiency Botto et al, 1992 HPRT Individual
Lesch-Nyhan
syndrome Marcus et al, 1993
DMD Kindred Duchenne’s muscular dystrophy
Hu et al, 1991
ADA Individual ADA deficiency-SCID Markert et al, 1988 Ins. Rec. β Individual Insulin-independent
diabetes Shimada et al, 1990
Antithrombin Individual Thrombophilia Olds et al, 1993 XY Individual XX male Rouyer et al, 1987 Lysyl hydroxylase Kindreds Ehlers-Danlos
syndrome Pousi et al, 1994
ALU/ALU RECOMBINATION AND CANCER
LOCUS DISTRIBUTION MECHANISM DISEASE REFERENCE10 xALL-1
Somatic Alu-Alu recombDup. intron 1-6
Acutemyelogenous
leukemia
Strout et al, 1998So et al, 1997;Schichman et al,1994
7 xBCR/Abl
Somatic X-Alu recomb. CML Jeffs et al, 1998Chen et al, 1989de Klein et al, 1986
All-1/AF9 Somatic Alu-Alutranslocation
Acutemyelogenous
leukemia
Super et al, 1997
2 xBRCA1
Somatic &A kindred
Alu-Alu recomb(del exon 17; del.
Promoter)
Breast cancer Puget et al, 1997Swensen et al,1997
2 xMLH1
2 kindreds Alu-Alu recomb.(del exon 16)(exons 13-16)
HNPCC Nystrom-Lahti etal, 1995Mauillon et al,1996
TRE Somatic InterchromosomalAlu-Alu recomb
Ewing's sarcoma Onno et al, 1992
RB Common Alu-Alu recomb.(799 bp del.)
Association withglioma
Rothberg et al,1997
EWS Subset of Africans Alu-Alu recomb.(del 2 kb)
Protective againstEwing Sarcoma?
Zucman-Rossi etal, 1997
7
8
גרמוכנראההטרנספוזוניםלשינויים, DNA-בלמוטציותובכךהגניםהתבטאותבתהליך
.גנטיתלשונותגרמו
AF217972
C9, NT_008541Alu
IIII IVII
AF010316
AF217965
AI972259
BE616884
BE614743
Sorek et al., 2002
Identification of alternatively spliced Alu exon
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.
elements Alu
pApA
Alu are Retrotransposons.
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
All introns of >1000 bp contain at least 1 Alu
9
Exsonization of Alu elements
Exon 1 Exon 2
Isoform A
Isoform B
ExonAlu
Exon 1
Exon 1
Exon 2
Exon 2
splicing
Alport
Sly
OATA
Origin of lifeWho’s first
DNA, RNA or Protein?
What is the advantage of having introns?
מהם התהליכים שעיצבו את הגנום האנושי
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 היצוריםמורכבים מאותן מולקולות ופועלים על סמך אותם .עקרונות
• All organisms are descendants of a single ancestral form of life. אב קדמון משותף האורגנזמיםהאם לכל?אחד
De duve ,chap1
10
Two Big Questions1. 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?
? החיים התפתחו מאב קדמון אחדהאורגנזמיםכיצד כל
Are we alone?
A. Yes
B. No
How do you think life originated on earth?
.AExtraterrestrial aliens brought it
.BCame with meteors from other planets
.CSome superhuman powers created it
.DChemical from primordial soup combined to make life
.ENone of the above
11
המפץ הגדול
12
History of Life
Stromatolites
Early prokaryotes
13
Cyanobacteria fossils
Possible Sources of Life’s Origin
DNARNAPROTEIN(Genetic (Information (Catalytic and Information)
and catalytic) Structural)
A. DNA
B. RNA
C. Protein
D. Carbohydrates
E. Lipids
Which came first?
14
Abiotic RNA Replication
Primitive RNA and Proteins
Which of the following is/are testable hypothesis about origin of life on
earth?.AExtraterrestrial aliens brought it.BCame with meteors from other planets.CSome superhuman powers created it.DChemical from primordial soup combined
to make life.ENone of the above
15
The Five Kingdom System
Domain Systems
16
17
18
19
20
21
22
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
23
Subsequent modifications of the atmosphere have produced representatives or precursors of all four organic macromolecular classes.
Including the molecules below:
Miller ExperimentIn 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 EarthWhen 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???
24
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 LifeSpontaneous generation •Mid-1800s—disproved by Louis Pasteur and John
Tyndall
Broth in flask is boiled to kill preexisting microorganisms.
Condensing water collectsas the broth cools, sealing
the mouth of the flask.
If neck is later broken off,outside air can carry
microorganisms into broth.
no growth growth
25
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
26
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!
Extra-terrestrial Origins
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
27
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 LifeEarly 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
28
The Origin of LifeEarly 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 LifeEarly 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 LifeEarly 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
29
The Origin of LifeEarly 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 LifeEarly 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
30
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
31
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
32
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
Ardipithecusramidus
Australopithecusafarensis
H. heidel-bergensis
A. boisei
A. africanus
A. robustus
H.habilis
H.sapiens
H. erectus
Homo ergaster
H. neanderthalensis
33
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
34
Panspermia
Possible Steps in the Origin of Life
Protobionts and Liposomes
35
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 LifeEarly Speculations
•More circumstantial evidence accumulated
–Astronomers found simple organic compounds in meteorites
–They were convinced that Earth’s initial atmosphere could not have matched Oparin-
Haldane’s model
36
The Origin of LifeEarly 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
37
1. Anaerobic, predatoryprokaryotic cell engulfsan aerobic bacterium.
2. Descendants of engulfedbacterium evolve intomitochondria.
3. Mitochondria-containingcell engulfs a photosyntheticbacterium.
4. Descendants of photosyntheticbacterium evolve into chloroplasts.
aerobicbacterium
תא בקטריאלי מול תא הומאני
38
Searching for the Origin
Domain Domain DomainBacteria Archaea Eukarya
Common Ancestor
1. Anaerobic, predatoryprokaryotic cell engulfsan aerobic bacterium.
2. Descendants of engulfedbacterium evolve intomitochondria.
3. Mitochondria-containingcell engulfs a photosyntheticbacterium.
4. Descendants of photosyntheticbacterium evolve into chloroplasts.
aerobicbacterium
39
RT
). יצור חד או רב תאי( תא – החיים בנויים באותו אופן האורגנזמיםכל תהליך התבטאות הגנים–כל התאים מפעילים את אותה תוכנית
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.
40
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
•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.
אב קדמון משותף 110 - 70לפני
.מליון שנה
MouseMouse--human human syntenysynteny.. Human chromosomes Human chromosomes can be cut into ~150 pieces, then shuffled into a can be cut into ~150 pieces, then shuffled into a reasonable approximation of the mouse genome. reasonable approximation of the mouse genome.
41
From 23 genes per million base pairs on From 23 genes per million base pairs on chromosome 19 (chromosome 19 (3%3%) to only 5 genes per ) to only 5 genes per million base pairs on chromosome 13 (million base pairs on chromosome 13 (0.7%0.7%).).
There are geneThere are gene--dense (urban centers) and dense (urban centers) and genegene--poor (deserts) chromosomespoor (deserts) chromosomes
959 cells959 cells 1,031 cells1,031 cells
19,000 genes19,000 genes 13,600 genes13,600 genes~10~1088 cellscells
KK--value paradox: Complexity value paradox: Complexity does not correlate with does not correlate with chromosome number.chromosome number.
46 250
Ophioglossum reticulatumHomo sapiens Lysandra atlantica
1260
42
CC--value paradox: Complexity value paradox: Complexity does not correlate with does not correlate with genome size.genome size.
3.4 × 10 9 bpHomo sapiens Amoeba dubia
6.7 × 1011 bp
NN--value paradox: Complexity value paradox: Complexity does not correlate with gene does not correlate with gene number.number.
~31,000 genes~31,000 genes ~26,000 genes~26,000 genes ~50,000 genes~50,000 genes
43
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 indifferent parts of the body.
תוצרי . גנים המתבטאים ברמות שונות ברקמות גופנומאקטבים שונים פרומוטוריםכך , יכולים להיות מעורבים בכמה מעגלים שונים בתוך התא– החלבונים –הגנים
.שתהיה להם יכולת לשלוט במספר תהליכים תוך תאיים ולתאם ביניהם
44
Retrovirus
Gene expression of virus
RT
ENV
האנושיהגנוםלהתהוותשגרמותהליכיםחדשותבפונקציותלהתמחותהשניהסטאתשיחררודופליקציהתהליכי
שונותשיוצרלתהליךגרמומוטציותהאוקריוטילגנוםפלשופרוקריוטיםגנים200-כ
האימוניתוהמערכתDNAתיקון, גניםהפעלותכמומערכותשלשיפור
שלהכמיהראקצית
splicing-ה
שלבית-דוראקציהראקציותהמורכבת משתי
עוקבותאסטרפיקציה-טראנס
lariat
The Exon Theory of Genes• Theory of origin of protein function• LUCA and before:
– 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
45
The Human Genome 2.91 billion base pair 26,000-38,000 genes 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
?לאינטרוניםבשביל מה אנחנו זקוקים
גנים50-100,000הערכה ראשונית דיברה על
קייםהיהשהגנוםלאחרהופיעוהאינטרוניםהאםintrons)? התהוותובמהלךאו first or invaded)
Introns Early, Introns LateTwo views of Life
• Introns Early• Eukaryotic nuclear
genome original• Prokaryotic genome
derived• Exons old• Exon shuffling old
form of gene increase
• Introns Late• Prokaryotic genome
original• Eukaryotic nuclear
genome derived• Exons young• Exon shuffling recent
form of gene increase
46
The network of RNA interactions in the spliceosome
snRNPה שלאבולוציה
47
The route of intron invasion of new chromosomal sites
מהגנים40% Alternative splicing
סוגים שונים של חלבוניםהנוצרים מאותו חלבון
איזופורמיםנקראים
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
48
The Path to DNA/proteins System
DNA /proteins
Abiotic world (דומם)
RNARNA--WorldWorld
stability
replication
flexibility
catalytic
Who Was First ? Proteins or Nucleic Acids?
Proteins
It is easier to polymerize proteins than nucleotides
Nucleic acids
special conditions in the soup enabled replication without proteins
Both
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 polymerizationRNA self
replicating without enzymes
RNA - proteins system
DNA-RNA-proteins system
1. How ?Who/Which?
2. Catalytic function ?
3. The path? mechanism
to path ?
49
proteins
23S rRNA
peptidyl transfer reaction:
P-site tRNA
5S rRNA
A-site tRNA
הבדלים בדפוסי התבטאות חלבונים בין מוח של אדם לשימפנזה
Chimpanzee Human
Origin of lifeWho’s first
DNA, RNA or Protein?
What is the advantage of having introns?
מהם התהליכים שעיצבו את הגנום האנושי