Class 37:
Secret of Life
CS200: Computer Science
University of Virginia
Computer Science
David Evans
http://www.cs.virginia.edu/~evans
From Lecture 15:
•
Liberal
Arts
Grammar: study of meaning in written
Quadrivium
Trivium
expression
BNF replacement rules for describing languages,
rules of evaluation for meaning
• Rhetoric: comprehension of
verbal and written discourse
YourNot
PS8
webInterfaces
sites arebetween
a discourse
yet…
components,
program
user
between user
and and
server.
• Logic: argumentative discourse
for discovering truth
Rules of evaluation, if,
recursive definitions
Learned
to count
Not much
yet…in
Lambda
Calculus
wait until
April
• Arithmetic: understanding numbers
• Geometry: quantification of space
• Music: number in time
• Astronomy
Curves as procedures,
fractals
Yes, even if we can’t figure out how to play
“Hey Jude!”
Yes: Neil deGrasse Tyson says so
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th
50
Today is the
anniversary of
announcement of the
most important
scientific discovery of
th
the 20 century!
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Eagle Pub,
Cambridge UK
“Watson, we have discovered the meaning of life!”
Francis Crick, 28 February 1953
“Watson, come here, I want to see you.”
Alexander Graham Bell, 10 March 1876
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Molecular
Structure of
Nucleic Acids,
“A Structure for
Deoxyribose
Nucleic Acid”,
Nature
25 April 1953
It has not escaped our notice that the specific pairing
we have postulated immediately suggests a possible
copying mechanism for the genetic material.
http://www.nature.com/genomics/human/watson-crick/watson_crick.pdf
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Brief History of Biology
1950
1850
Life is
about
magic.
(“vitalism”)
Life is
about
chemistry.
Most biologists work on Classification
Aristotle (~300BC) - genera and species
Life is
about
computation.
Schrödinger (1944)
life is information
crack the information code
Descartes (1641)
explain life mechanically
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Life is
about
information.
2000
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Watson and Crick (1953)
DNA stores the information
6
DNA
• Sequence of
nucleotides: adenine
(A), guanine (G),
cytosine (C), and
thymine (T)
• Two strands, A must
attach to T and G must
attach to C
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G
C
T
A
7
Central Dogma of Biology
Translation
Transcription
DNA
RNA
Protein
Image from http://www.umich.edu/~protein/
• RNA makes copies of DNA segments
• RNA describes sequences of amino acids
• Chains of amino acids make proteins
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Encoding Proteins
• There are 4 nucleotides: adenine (A),
guanine (G), cytosine (C), and thymine (T)
(replaced with uracil (U) in RNA)
• There are 20 different amino acids, and a
stop marker (to separate proteins)
• How many nucleotides are needed to
encode one amino acid?
with 2, could encode 16 things: 4 * 4
with 3, could encode 64 things: 4 * 4 * 4
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Codons
• Three nucleotides
encode an amino
acid
• But, there are only
20 amino acids, so
there may be
several different
ways to encode
the same one
From http://web.mit.edu/esgbio/www/dogma/dogma.html
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How Big is the
Make-a-Human Program?
• 3 Billion Base Pairs
– Each nucleotide is 2 bits (4 possibilities)
– 3 B pairs * 1 byte/4 pairs = 750 MB
• Every sequence of 3 base pairs one of 20
amino acids (or stop codon)
– 21 possible codons, but 43 = 64 possible
– So, really only 750MB * (21/64) ~ 250 MB
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1 CD ~ 650 MB
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People are almost all the Same
• Genetic code for 2 humans differs in only
2.1 million bases
– 4 million bits = 0.5 MB
• How big is 0.5MB?
– 1/3 of a floppy disk
– ~22 times the size of the PS6 adventure
game code
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Is DNA Really a
Programming Language?
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Stuff Programming Languages
are Made Of
• Primitives
codons (sequence of 3 nucleotides that encodes a protein)
• Means of Combination
?? Morphogenesis? Not well understood (by anyone).
This is where most of the expressiveness comes from!
• Means of Abstraction
DNA itself – separate proteins from their encoding
Genes – group DNA by function (sort of)
Chromosomes – package Genes together
Organisms – packages for reproducing Genes
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My Research Group
• Build robust, survivable systems from
unreliable components
– Learn from biological systems that do this
• Cell-Based Programming Model
– Genes turn on and off  state changes
– Emit different chemicals depending on state,
sense chemicals in surroundings
– Cells can divide asymmetrically
– Lots of simplifications: not simulating reality
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Example
A
alive < 1
alive > 0
B
alive < 1
& radius > 1
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state A
emits (alive, 1) diffuses (radius, 10)
transitions
(alive < 1) from any direction
-> (A, B) in same direction;
-> (A);
state B
emits (alive, 1)
transitions
(alive < 1) from any direction & (radius > 1)
-> (B, B) in same direction;
(alive > 0) from any direction -> (B);
-> (radius);
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Simulating Program
A
alive < 1
alive > 0
B
alive < 1
& radius > 1
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Simulation by Selvin George
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Simulation by Selvin George
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Complexity
Molecular map of colon cancer cell
from http://www.gnsbiotech.com/applications.shtml
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Computing with DNA
Leonard Adleman
(Mathematical
Consultant for
Sneakers), 1995
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Hamiltonian Path Problem
• Input: a graph, start vertex and end vertex
• Output: either a path from start to end that
touches each vertex in the graph exactly
once, or false indicating no such path
exists
RIC
start: CHO
end: BWI
BWI
CHO
IAD
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How hard is the
Hamiltonian path
problem?
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Encoding The Graph
• Make up a two random 4-nucleotide
sequences for each city:
CHO:
RIC:
IAD:
BWI:
CHO1 = ACTT
RIC1 = TCGG
IAD1 = GGCT
BWI1 = GATC
CHO2 = gcag
RIC2 = actg
IAD2 = atgt
BWI2 = tcca
• If there is a link between two cities (AB),
create a nucleotide sequence: A2B1
CHORIC
RICCHO
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gcagTCGG
actgACTT
CS 200 Spring 2003
Based on Fred Hapgood’s notes
on Adelman’s talk
http://www.mitre.org/research/nanotech/hapgo
od_on_dna.html
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Encoding The Problem
• Each city nucleotide sequence binds with
its complement (A  T, G  C) :
CHO: CHO1 = ACTT
CHO2 = gcag
CHO’:
TGAA
cgtc
RIC:
TCGGactg
RIC’: AGCCtgac
IAD:
GGCTatgt IAD’ = CCGAtaca
BWI: GATCtcca BWI’ = CTAGaggt
• Mix up all the link and complement DNA
strands – they will bind to show a path!
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Path Binding
BWI’
RIC’
IAD’
CHO’
TGAAcgtcCCGAtacaAGCCtgacCTAGaggt
gcagGGCTatgtTCGG actgGATC
CHOIAD IADRIC RICBWI
TCGGactg
RIC
BWI
GATCtcca
CHO
ACTTgcag
IAD
GGCTatgt
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Getting the Solution
• Extract DNA strands starting with CHO
and ending with BWI
– Easy way is to remove all strands that do not
start with CHO, and then remove all strands
that do not end with BWI
• Measure remaining strands to find ones
with the right weight (7 * 8 nucleotides)
• Read the sequence from one of these
strands
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Why don’t we use DNA computers?
• Speed: shaking up the DNA strands does
1014 operations per second ($400M
supercomputer does 1010)
• Memory: we can store information in DNA
at 1 bit per cubic nanometer
• How much DNA would you need?
– Volume of DNA needed grows exponentially
with input size
– To solve ~45 vertices, you need ~20M gallons
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DNA-Enhanced PC
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Biology is (becoming) a
subfield of Computer Science
• Biological mechanisms are mostly
understood (proteomics still has a way
to go)
• What is not understood is how those are
combined to create meaning
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PS8
• Before 10:55am Monday:
– Submit a zip file of all your code using a form linked from
the CS200 web site
– If you want to use a few PowerPoint slides in your
presentation, you may submit those also
• You only have 3 or 5 minutes: use them wisely
– Figure out beforehand what you will do
– Recommend: one team member drive web browser, one
(or two) talk
– Talk about what users should know about your website, not
about how you built it (unless there is something especially
interesting)
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McIntire Symposium Talk: Daniel Kahneman
(Psychologist, Nobel Prize in Economics)
• When you are 99% sure, how often are you
actually right?
– 85-90% of the time
– Some of you will get a sticker on your Exam 2 that will
make you 99.5% sure of the lowest grade you could
receive in CS200 (the 0.5% is since you still need to do
PS8 well)
• Humans are overly optimistic and excessively risk
averse
– No risk in taking the final: it cannot lower your grade
– You should be optimistic that it can help your grade
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Final
• Out Monday, due Monday, May 5 (4:55pm)
• You have 8 days, but should not spend
more than 4 hours on the exam
• Will include:
– A small programming problem (like a PS)
– Some questions about computability and
complexity
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Graduation Photo
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