Download Lecture 1 - Graham Ellis

Computational Molecular Biology
Lecture One
Semester I, 2009-10
Graham Ellis
NUI Galway, Ireland
Abstract
This is a mathematics course about biology and computation. It is
not a biology course.
No previous knowledge of computers or biology assumed.
Text
Course loosely based on the book:
Computational Molecular Biology: An algorithmic approach
Pavel A. Pevzner (MIT Press, 2000)
Learning Outcomes
By Christmas, diligent students should be able to
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Use some basic terminology of molecular biology (gene, DNA,
alignment, edit distance, . . . ).
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Describe some fundamental computational problems in
molecular biology.
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Use some basic computer science jargon (algorithm, dynamic
programming, loop, object oriented programming, . . . ).
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Read and write simple algorithms.
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Implement simple algorithms on a PC using the Python
programming language.
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Be aware of the existence and purpose of bioinformatics
software such as BLAST.
Assessment
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Two practical homework assignments (10% each).
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End of semester written exam (80%) (based on the lecture
notes, exercise sheets and homework assignments).
Problem solving
Some time in lectures will be devoted to solving problems from
exercise sheets. (There will be no extra tutorial.)
Prerequisites
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1st year mathematics
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Access to a PC.
Q: What is a gene?
Q: What is a gene?
A: I don’t really know!
Q: What is a gene?
A: I don’t really know!
Q: What is electricity?
Q: What is a gene?
A: I don’t really know!
Q: What is electricity?
A: I don’t really know, but my limited understanding enables me to
wire a house and build a simple radio.
Some Elementary Biology
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Darwin & others aware of inheritance. Believed in blended
inheritance: offspring are an average of their parents.
Some Elementary Biology
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Darwin & others aware of inheritance. Believed in blended
inheritance: offspring are an average of their parents.
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Gregor Mendel studied inheritance in pea plants (1860s).
Noticed that biological variations only inherited as discrete
traits.
e.g. offspring of a blue eyed mother and brown eyed father
has 3/4 chance of having brown eyes.
Some Elementary Biology
◮
Darwin & others aware of inheritance. Believed in blended
inheritance: offspring are an average of their parents.
◮
Gregor Mendel studied inheritance in pea plants (1860s).
Noticed that biological variations only inherited as discrete
traits.
e.g. offspring of a blue eyed mother and brown eyed father
has 3/4 chance of having brown eyes.
◮
In 1889 Hugo de Vries gave Mendel’s inheritance mechanism
the name gene. Had little understanding of the physical
nature of a gene.
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In 1910 Thomas Hunt Morgan showed that genes resided in
chromosomes in cells.
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In 1910 Thomas Hunt Morgan showed that genes resided in
chromosomes in cells.
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In 1944 it was shown that Deoxyribonucleic acid, or DNA,
holds the genes information. DNA is a long polymer made
from repeating units called nucleotides.
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In 1910 Thomas Hunt Morgan showed that genes resided in
chromosomes in cells.
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In 1944 it was shown that Deoxyribonucleic acid, or DNA,
holds the genes information. DNA is a long polymer made
from repeating units called nucleotides.
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In 1953 Crick and Watson demonstrated the molecular
structure of DNA.
Where is DNA?
DNA condensed into
little holes
chromosomes
1
cell
boundary
2
2’
1’
nuclear
membrane
Chromosomes contain a mixture of protein and DNA. They often
come in pairs.
Humans cells contain 46 chromosomes in 22 homologous pairs plus
the non-homologous X and Y chromosomes that determine sex.
How big is DNA?
1m
10−2 m
10−5 m
10−8 m
very roughly, the height of person
length of DNA from a human chromosome
diameter of typical human cell
diameter of a DNA thread
How big is DNA?
1m
10−2 m
10−5 m
10−8 m
very roughly, the height of person
length of DNA from a human chromosome
diameter of typical human cell
diameter of a DNA thread
An imaginary scale
On a scale where humans were 1000km tall, a typical human
chromosome would contain 10km of DNA. This would be
contained in a cell of 1m diameter. The DNA thread would have a
1mm diameter.
Why is DNA important?
1. DNA contains the instructions needed to construct other
components of cells such as protein and RNA.
Why is DNA important?
1. DNA contains the instructions needed to construct other
components of cells such as protein and RNA.
2. There are 20 different kinds of amino acid that combine to
make proteins. There are many possible combinations,
resulting in many different types of protein.
Why is DNA important?
1. DNA contains the instructions needed to construct other
components of cells such as protein and RNA.
2. There are 20 different kinds of amino acid that combine to
make proteins. There are many possible combinations,
resulting in many different types of protein.
3. The cell DNA tells a cell the order in which to assemble the
amino acids, and the length to be assembled.
What is DNA?
(An overly simple, yet sufficient, answer)
DNA is a string of four different nucleotides: Adenine, Guanine,
Cytosine and Thymine.
DNA thread
gene 1
gene 2
T T T A A A A A G G C T
gene 3
part of
gene 2
genetic code
amino acids
Phe −−− Lys −−− Lys −−− Ala
part of
protein 2
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For the purposes of this course (and much of computational
biology) we can view DNA as a string in the four-letter
alphabet of nucleotides A, T, G and C.
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For the purposes of this course (and much of computational
biology) we can view DNA as a string in the four-letter
alphabet of nucleotides A, T, G and C.
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The entire DNA of an organism is called its genome
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Each cell of an organism contains the same genome.
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For the purposes of this course (and much of computational
biology) we can view DNA as a string in the four-letter
alphabet of nucleotides A, T, G and C.
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The entire DNA of an organism is called its genome
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Each cell of an organism contains the same genome.
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DNA is usually double stranded with one strand being the
Crick-Watson complement of the other. (T pairs with A, C
with G.)
A T G C T C A G G
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T A C G A G T C C