Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the...
-
date post
18-Dec-2015 -
Category
Documents
-
view
219 -
download
0
Transcript of Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the...
![Page 1: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/1.jpg)
Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object
The Human Genome, and Human ComplexityYoni Toker
![Page 2: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/2.jpg)
ViewpointGENE NUMBER:
What If There Are Only 30,000 Human Genes?Jean-Michel Claverie
Humans: ~ 30,000 genes
Worm (Caenorhabditis elegans) :~20,000 genes
Are we not much more complicated than worms?
Science 16 February 2001:Vol. 291. no. 5507, pp. 1255 - 1257
![Page 3: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/3.jpg)
Mapping of the Human genome
1953Rosalind Franklin, James Watson and Francis Crick discover the double helical structure of DNA.
Mid 1980’sHuman Genome Project Suggested
![Page 4: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/4.jpg)
Objections to the Human Genome Project
•Too hard:Human genome is 3e+9 base pairs long. A lab (in the 1980’s) could sequence 500 base pairs a day.
3e+9/500/365~~16,000
Base pairs
BP’s a day
Days a year
years
![Page 5: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/5.jpg)
Objections to the Human Genome Project
•Too hard:Human genome is 3e+9 base pairs long. A lab (in the 1980’s) could sequence 500 base pairs a day.
•Too expensive!
•Not the way to do biology:
Biology is hypothesis driven experiments, not a fishing expedition
![Page 6: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/6.jpg)
Mapping of the Human genome1953Rosalind Franklin, James Watson and Francis Crick discover the double helical structure of DNA.
Mid 1980’sHuman Genome Project Suggested
1990Human Genome project announced: Goal: sequence the entire human genome in 15 years, with a budget of $3 billion
Comparison:LHC budget ~5 billionAircraft carrier ~10 billion
![Page 7: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/7.jpg)
Mapping of the Human genome1953Rosalind Franklin, James Watson and Francis Crick discover the double helical structure of DNA.
Mid 1980’sHuman Genome Project Suggested
1990Human Genome project announced: Goal: sequence the entire human genome in 15 years, with a budget of $3 billion
1998Only 5% of genome sequenced
I (Celera) will decode the entire human genome in just 3 years with
a budget of only $300 Million Dollars
![Page 8: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/8.jpg)
Sequencing small pieces of DNA
A C G TA
C T
primer A C
G
TAA
C
F. Sanger et al., Nature 265, 687 (1977).
E. C. Strauss, J. A. Kobori, G. Siu, L. E. Hood, Anal.Biochem. 154, 353 (1986).
![Page 9: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/9.jpg)
Sequencing small pieces of DNAA C G TAprimer A C
A C G TAprimer A C
A C G TAprimer A C
A C G TAprimer A C
A C G TAprimer A C
A C G TAprimer A C
T G
T G C
T G C AT T
T G C
T G C T
T
![Page 10: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/10.jpg)
T G
T G C
T G C AT T
T G C
T G C T
T
Sequencing small pieces of DNA
![Page 11: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/11.jpg)
Sequencing Large DNAsThe whole shotgun method
![Page 12: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/12.jpg)
Fierce competition .. Comes to a drawJune 26, 2000 President Clinton, with J. Craig Venter, left, and Francis Collins, announces completion of "the first survey of the entire human genome."
![Page 13: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/13.jpg)
Technology is getting better: Solexa sequencing
![Page 14: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/14.jpg)
Technology is getting better!
1960 1970 1980 1990 200010
0
102
104
106
108
1010
Year of Publication
size
of l
arg
est
pro
ject
(b
p)
SequencingSyntheis
1e+5
![Page 15: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/15.jpg)
A
DMT
A
DMT
C
A
A
C
A
A
G
T
T
G
T
T
Oligonucleotide Synthesis
• 1) De-Blocking dichloroacetic acid (DCA) or trichloroacetic acid in dichloromethane (DCM)
DMT= dimethoxytrity
![Page 16: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/16.jpg)
A A
C
A
A
C
A
A
Oligonucleotide Synthesis
• 1) De-BlockingC
DMT
C
DMT
C
DMT
C
DMT
•2) Base Condensation
![Page 17: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/17.jpg)
A A
C
A
A
C
A
A
Oligonucleotide Synthesis
• 1) De-Blocking
C
DMT
•2) Base Condensation
•3) Capping
•4) Oxidation
![Page 18: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/18.jpg)
A A
C
A
A
C
A
A
Oligonucleotide Synthesis
• 1) De-Blocking
C
DMT
•2) Base Condensation
•3) Capping
•4) Oxidation
A
DMTA
DMT
![Page 19: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/19.jpg)
DNA Synthesis
![Page 20: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/20.jpg)
Genetic Code
4 base pairs 20 amino acids
Example:
CCG Proline
Every 3 base pairs code for an amino acid
![Page 21: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/21.jpg)
From DNA to Proteins
![Page 22: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/22.jpg)
Some of the things we learned
•Human genome contains 3e+9 base pairs
•Less then 2% of the genome is genes
•Gene average length 3,000 base pairs
•Number of genes ~30,000
•98% genes identical between all people:
only 1-2% of genes responsible for color of eyes, genetic diseases…
![Page 23: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/23.jpg)
SpeciesSize of genomeNumber of genesHuman
2900 e+6 base pairs30,000
Fruit fly (Drosophila melanogaster)120 e+6 base pairs13,601
Baker's yeast (Saccharomyces
cerevisiae)12 e+6 base pairs 6 ,275
Worm (Caenorhabditis elegans)97 e+6 base pairs19,000
E. coli4.1 e+6 base pairs 4,800
Arabidopsis (Arabidopsis thaliana)125 e+6 base pairs25,000
Genome Size
![Page 24: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/24.jpg)
ViewpointGENE NUMBER:
What If There Are Only 30,000 Human Genes?Jean-Michel Claverie
Humans: ~ 30,000 genes
Worm (Caenorhabditis elegans) :~20,000 genes
Are we not much more complicated than worms?
Science 16 February 2001:Vol. 291. no. 5507, pp. 1255 - 1257
![Page 25: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/25.jpg)
ViewpointGENE NUMBER:
What If There Are Only 30,000 Human Genes?Jean-Michel Claverie
•Are we really more complicated then flies and worms?
• 30,000 is much more complicated then 20,000
• Gene number isn’t everything
![Page 26: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/26.jpg)
210,000
30,000 is much more complicated then 20,000
230,000
220,000
103000~~
![Page 27: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/27.jpg)
Gene Number isn’t everything
mRNA
30,000 genes, but more than 85,000 mRNA species
Alternative splicingmRNA editing
![Page 28: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/28.jpg)
Vertebrate Immune System
Gene sites
Anti body
Complexity comes from more sophisticated regulation mechanisims!
![Page 29: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/29.jpg)
More sophisticated methods of gene expression and regulation
…
mRNA editing Proteins change their function:•Number of sugars attached•Folding/Unfolding•….
mRNA
![Page 30: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/30.jpg)
Genetic Networks
Calverie:Every gene connected on average to 4-5 other genes
We are not much more complicated then an airplane!
But: Genetic networks follow a power law distribution
![Page 31: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/31.jpg)
Genetic Networks
Number of connections
Average is not very meaningful!
![Page 32: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/32.jpg)
Summary
Human Genome Project •Decoding the “part list” of humans
•Extraordinary technological advances
Complexity: Genome is just the beginning
Aim High!Dream On!
![Page 33: Kolmogorov: Complexity of an object is the shortest length of a computer program that creates the object The Human Genome, and Human Complexity Yoni Toker.](https://reader035.fdocuments.us/reader035/viewer/2022062320/56649d245503460f949fa522/html5/thumbnails/33.jpg)
Aim High Dream On!
•Sequence more and more organisms
•Creation of Synthetic life
•Find the genes for genetic diseases
•Reconstruct the tree of life
•Learn more of nature’s tricks
• DNA nanotechnology
• Producing clean energy, depositing C02…