DNA לש םיטנמלא םינוזופסנרט םונגהךותבםוקמלםוקממםירבועשgilast/course2009/pdf/10Origin_of_lifeShort.pdf · 3 Transposon-derived repeats!!!ישונאה

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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.

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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

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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

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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)

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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

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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

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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

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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

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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

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המפץ הגדול

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History of Life

Stromatolites

Early prokaryotes

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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?

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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

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The Five Kingdom System

Domain Systems

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17

18

19

20

21

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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

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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???

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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

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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

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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

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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

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•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


•Phospholipids arrange themselves into bubbles

–Eventually they reach a level of complexity

•Called protocells (not living)

•Still can’t reproduce, no DNA


•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

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•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


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

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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

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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

•


•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

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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

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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

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Panspermia

Possible Steps in the Origin of Life

Protobionts and Liposomes

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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


•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

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•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

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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

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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

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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.

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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

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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

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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 ?

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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

Documents

DNA לש םיטנמלא םינוזופסנרט םונגהךותבםוקמלםוקממםירבועשgilast/course2009/pdf/10Origin_of_lifeShort.pdf · 3 Transposon-derived repeats!!!ישונאה