Download Origin of life

‫‪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