Algorithms in Bioinformatics: A

Practical Introduction
Introduction to Molecular Biology

Outline

Cell
DNA, RNA, Protein
Genome, Chromosome, and Gene
Central Dogma (from DNA to Protein)
Mutation
List of biotechnology tools
Brief History of Bioinformatics

Our body

Our body consists of a number of

organs
Each organ composes of a number of
tissues
Each tissue composes of cells of the
same type.

Cell

Cell performs two type of functions:

Perform chemical reactions necessary to maintain

our life
Pass the information for maintaining life to the
next generation

Actors:

Protein performs chemical reactions

DNA stores and passes information
RNA is the intermediate between DNA and
proteins

Protein

Protein is a sequence composed of an

alphabet of 20 amino acids.

The length is in the range of 20 to more than

5000 amino acids.
In average, protein contains around 350 amino
acids.

Protein folds into three-dimensional shape,

which form the building blocks and perform
most of the chemical reactions within a cell.

Amino acid

Each amino acid consist of

Amino
group

Amino group
Carboxyl group
R group

NH2

Carboxyl group

R
C
(the central carbon)

OH

R group

Classification of amino acids (I)

20 common amino acids can be classified into

4 types.

Positively charged (basic) amino acids:

Arginine (Arg, R)
Histidine (His, H)
Lysine (Lys, K)

Negatively charged (acidic) amino acids:

Aspartic acid (Asp, D)

Glutamic acid (Glu, E)

Classification of amino acids

(II)

Polar amino acids:

Overall uncharged, but uneven charge distribution.

Can form hydrogen bonds with water. They are
called hydrophilic. Often found on the outer
surface of a folded protein.

Asparagine (Asn, N)
Cysteine (Cys, C)
Glutamine (Gln, Q)
Glycine (Gly, G)
Serine (Ser, S)
Threonine (Thr, T)
Tyrosine (Tyr, Y)

Classification of amino acids

(III)

non-polar amino acids:

Overall uncharged and uniform charge distribution.

Cannot form hydrogen bonds with water. They are
called hydrophobic. Tend to appear on the inside
surface of a folded protein.

Alanine (Ala, A)
Isoleucine (Ile, I)
Leucine (Leu, L)
Methionine (Met, M)
Phenylalanine (Phe, F)
Proline (Pro, P)
Tryptophan (Trp, W)
Valine (Val, V)

Summary of the amino acid properties

Amino Acid
Alanine
Cysteine
Aspartic acid
Glutamic acid
Phenylalanine
Glycine
Histidine
Isoleucine
Lysine
Leucine
Methionine
Asparagine
Proline
Glutamine
Arginine
Serine
Threonine
Valine
Tryptophan
Tyrosine

1-Letter
A
C
D
E
F
G
H
I
K
L
M
N
P
Q
R
S
T
V
W
Y

3-Letter
Ala
Cys
Asp
Glu
Phe
Gly
His
Ile
Lys
Leu
Met
Asn
Pro
Gln
Arg
Ser
Thr
Val
Trp
Tyr

Avg. Mass (Da) volume

89.09404
67
121.15404
86
133.10384
91
147.13074
109
165.19184
135
75.06714
48
155.15634
118
131.17464
124
146.18934
135
131.17464
124
149.20784
124
132.11904
96
115.13194
90
146.14594
114
174.20274
148
105.09344
73
119.12034
93
117.14784
105
204.22844
163
181.19124
141

Side
chain
polarity
non-polar
polar
polar
polar
polar
polar
polar
non-polar
polar
non-polar
non-polar
polar
non-polar
non-polar
non-polar
polar
polar
non-polar
polar
non-polar

Side chain
Hydropathy
acidity or
index
basicity
Neutral
1.8
basic (strongly)
-4.5
Neutral
-3.5
acidic
-3.5
neutral
2.5
acidic
-3.5
neutral
-3.5
neutral
-0.4
basic (weakly)
-3.2
neutral
4.5
neutral
3.8
basic
-3.9
neutral
1.9
neutral
2.8
neutral
-1.6
neutral
-0.8
neutral
-0.7
neutral
-0.9
neutral
-1.3
neutral
4.2

Nonstandard amino acids

Two non-standard amino acids which can be specified by

genetic code:

Non-standard amino acids which do not appear in protein:

Selenocysteine is incorporated into some proteins at a UGA codon,

which is normally a stop codon.
Pyrrolysine is used by some methanogenic archaea in enzymes that
they use to produce methane. It is coded for with the codon UAG.
E.g. lanthionine, 2-aminoisobutyric acid, and dehydroalanine
They often occur as intermediates in the metabolic pathways for
standard amino acids

Non-standard amino acids which are formed through

modification to the R-groups of standard amino acids:

E.g. hydroxyproline is made by a posttranslational modification of

proline.

Polypeptide
Protein or polypeptide chain is formed by joining the amino
acids together via a peptide bond.
One end of the polypeptide is the amino group, which is called
N-terminus. The other end of the polypeptide is the carboxyl
group, which is called C-terminus.

NH2

OH + NH2

R
NH2

Peptide bond

OH
H

OH

Protein structure

Primary structure

Secondary structure

The local structure formed by hydrogen bonding:

-helices and -sheets.

Tertiary structure

The amino acid sequence

The interaction of -helices and -sheets due to

hydrophobic effect

Quaternary structure

The interaction of more than one protein to form

protein complex

DNA

DNA stores the instruction needed by

the cell to perform daily life function.
It consists of two strands which
interwoven together and form a double
helix.
Each strand is a chain of some small
molecules called nucleotides.

Nucleotide for DNA

Nucleotide consists of three parts:

Deoxyribose
Phosphate (bound to the 5 carbon)
Base (bound to the 1 carbon)
N
N

OH

Phosphate

HO P O CH3

Base
(Adenine)

O
H

H
3

OH

H
2

Deoxyribose

More on bases
There are 5 different nucleotides: adenine(A),
cytosine(C), guanine(G), thymine(T), and uracil(U).
A, G are called purines. They have a 2-ring structure.
C, T, U are called pyrimidines. They have a 1-ring
structure.
DNA only uses A, C, G, and T.

N
N

N
N
Adenine

N
N

N
N
Guanine

N
Thymine

N
N

N
Cytosine

N
Uracil

Watson-Crick rules

Complementary bases:

A with T (two hydrogen-bonds)

C with G (three hydrogen-bonds)
C

A
T

10

10

Reasons behind the

complementary bases

Purines (A or G) cannot pair up because

they are too big
Pyrimidines (C or T) cannot pair up
because they are too small
G and T (or A and C) cannot pair up
because they are chemically
incompatible

Orientation of a DNA

One strand of DNA is generated by chaining together

nucleotides.
It forms a phosphate-sugar backbone.
It has direction: from 5 to 3. (Because DNA always
extends from 3 end.)
Upstream: from 5 to 3
Downstream: from 3 to 5
P

Double stranded DNA

Normally, DNA is double stranded within a cell.

The two strands are antiparallel. One strand is
the reverse complement of another one.
The double strands are interwoven together
and form a double helix.
One reason for double stranded is that it eases
DNA replicate.

Circular form of DNA

DNA usually exists in linear form

E.g. in human, yeast, exists in linear form

In some simple organism, DNA exists in

circular form.

E.g. in E. coli, exists in circular form

What is the locations of DNAs

in a cell?

Two types of organisms: Prokaryotes and

Eukaryotes.
In Prokaryotes: single celled organisms with
no nuclei (e.g. bacteria)

DNA swims within the cell

In Eukaryotes: organisms with single or

multiple cells. Their cells have nuclei. (e.g.
plant and animal)

DNA locates within the nucleus.

Some terms related to DNA

Genome
Chromosome
Gene

Chromosome

Usually, a DNA is tightly wound around

histone proteins and forms a chromosome.
The total information stored in all
chromosomes constitute a genome.
In most multi-cell organisms, every cell
contains the same complete set of genome.

May have some small different due to mutation

Example:

Human Genome: has 3G base pairs, organized in

23 pairs of chromosomes

Gene

A gene is a sequence of DNA that encodes a

protein or an RNA molecule.
In human genome, it is expected there are
30,000 35,000 genes.
For gene that encodes protein,

In Prokaryotic genome, one gene corresponds to

one protein
In Eukaryotic genome, one gene can corresponds
to more than one protein because of the process
alternative splicing (discuss later!)

Complexity of the organism vs.

genome size

Human Genome: 3G base pairs

Amoeba dubia (a single cell organism): 670G base
pairs

Thus, genome size has no relationship with the

complexity of the organism

Number of genes vs. genome

size

Prokaryotic genome: E.g. E. coli

Eukaryotic genome: E.g. Human

Number of base pairs: 5M

Number of genes: 4k
Average length of a gene: 1000 bp

Note that before 2001,

the people think we
have 100000 genes

Number of base pairs: 3G

Estimated number of genes: 20k 30k
Estimated average length of a gene: 1000-2000 bp

Note that 90% of the E. coli genome consists of coding regions.

Less than 3% of the human genome is believed to be coding
regions. The rest is called junk DNA.
Thus, for Eukaryotic genome, the genome size has no
relationship with the number of genes!

RNA

RNA has both the properties of DNA

and protein

Similar to DNA, it can store and transfer

information
Similar to protein, it can form complex 3dimensional structure and perform some
functions.

Nucleotide for RNA

Nucleotide consists of three parts:

Ribose Sugar (has an extra OH group at 2)

Phosphate (bound to the 5 carbon)
Base (bound to the 1 carbon)
Base
(Adenine)
5`
4`

Phosphate

1`

3`
2`

Ribose Sugar

RNA vs DNA

RNA is single stranded.

The nucleotides of RNA are quite similar to
that of DNA, except that it has an extra OH at
position 2. (see previous slide!)

Due to this extra OH, it can form more hydrogen

bonds than DNA. Thus, RNA can form complexity
3-dimensional structure.

RNA use the base U instead of T.

U is chemically similar to T. In particular, U is also

complementary to A.

Non-coding RNA

transfer RNA (tRNA)

ribosomal RNA (rRNA)
small RNAs including

snoRNAs
microRNAs
siRNAs
piRNAs

long ncRNAs

Examples: Xist, Evf, Air, CTN and PINK

People expected there are over 30k long ncRNAs.

microRNA (miRNA) (I)

miRNA is a single-stranded RNA of length

~22.
Its formation is as follows:

miRNA is encoded as a non-coding RNA.

It first transcribed as a primary transcript
called primary miRNA (pri-miRNA).
It then cleaved into a precursor miRNA (premiRNA) with the help of the nuclease
Drosha. Precursor miRNA is of length ~6080 nt and can potentially fold into a stemloop structure.
The pre-miRNA is transported into the
cytoplasm by Exportin 5. It is further cleaved
into a maturemiRNA by the endonuclease
Dicer.

genome
pri-miRNA
pre-miRNA
miRNA

RNA interference

Suppose an miRNA is partially complementary to an mRNAs.

When miRNA is integrated with the RNA-induced silencing
complex (RISC),

Naturally, RNA interference are used

It down-regulate the mRNA by either translational repression or

mRNA cleavage.
as a cell defense mechanism that represses the expression of viral
genes.
to regulate development

We now apply it to knockdown our gene targets.

In 2006, Andrew Fire and Craig C. Mello shared the Nobel Prize
in Physiology or Medicine for their work on RNA interference in
C. elegans.

Replicate or Repair of DNA

DNA is double stranded.

When the cells divide,

DNA needs to be duplicated and passes to the two

daughter cells.
With the help of DNA polymerase, the two strands
of DNA serve as template for the synthesis of
another complementary strands, generating two
identical double stranded DNAs for the two
daughter cells.

When one strand is damaged,

it is repaired with the information of another

strand.

Mutation

Despite the near-perfect replication,

infrequent unrepaired mistakes are still
possible.

Occasionally, some mutations make the cells

or organisms survive better in the
environment.

Those mistakes are called mutations.

The selection of the fittest individuals to survive is

called natural selection.

Mutation and natural selection have resulted

in the evolution of a diversified organisms.

Mutation

Mutation is the change of

genome by sudden
It is the basis of evolution
It is also the cause of cancer
Note: mutation can occur in
DNA, RNA, and Protein

Central Dogma

Central Dogma tells us how we get the protein from

the gene. This process is called gene expression.
The expression of gene consists of two steps

Transcription: DNA mRNA

Translation: mRNA Protein
Post-translation Modification: Protein Modified protein

RNA

DNA

AAAA

Protein

Modified Protein

Central Dogma for Procaryotes

DNA
transcription

translation

modification

cytoplasm

Transcription (Procaryotes)
Synthesize a piece of RNA (messenger RNA,
mRNA) from one strand of the DNA gene.

1.

2.

3.
4.

An enzyme RNA polymerase temporarily

separates the double-stranded DNA
It begins the transcription at the transcription
start site.
A A, CC, GG, and TU
Once the RNA polymerase reaches the
transcription start site, transcription stop.

Translation
Translation synthesizes a protein from a mRNA.
In fact, each amino acids are encoded by consecutive
sequences of 3 nucleotides, called codon.
The decoding table from codon to amino acid is called genetic
code.
Note:

There are 43=64 different codons. Thus, the codons are not oneto-one correspondence to the 20 amino acids.
All organisms use the same decoding table!
The codons that encode the same amino acid tend to have the
same first and second nucleotide.
Recall that amino acids can be classified into 4 groups. A single
base change in a codon is usually not sufficient to cause a codon
to code for an amino acid in different group.

Genetic
code

Start codon:
ATG (also
code for M)
Stop codon:
TAA, TAG,
TGA

TTT
TTC
TTA
TTG

Phe
Phe
Leu
Leu

[F]
[F]
[L]
[L]

TCT
TCC
TCA
TCG

Ser
Ser
Ser
Ser

[S]
[S]
[S]
[S]

TAT Tyr [ Y]
TAC Tyr [Y]
TAA Ter [end]
TAG Ter [end]

TGT Cys [C]

TGC Cys [C]
TGA Ter [end]
TGG Trp [W]

T
C
A
G

CTT
CTC
C
CTA
CTG

Leu
Leu
Leu
Leu

[L]
[L]
[L]
[L]

CCT
CCC
CCA
CCG

Pro
Pro
Pro
Pro

[P]
[P]
[P]
[P]

CAT
CAC
CAA
CAG

His
His
Gln
Gln

[H]
[H]
[Q]
[Q]

CGT
CGC
CGA
CGG

Arg
Arg
Arg
Arg

[R]
[R]
[R]
[R]

T
C
A
G

AT T
AT C
A
ATA
ATG

Ile
Ile
Ile
Met

[I]
[I]
[I]
[M]

ACT
ACC
ACA
ACG

Thr
Thr
Thr
Thr

[T]
[T]
[T]
[T]

AAT
AAC
AAA
AAG

Asn
Asn
Lys
Lys

[N]
[N]
[K]
[K]

AGT
AGC
AGA
AGG

Ser
Ser
Arg
Arg

[S]
[S]
[R]
[R]

T
C
A
G

GTT
GTC
G
GTA
GTG

Val
Val
Val
Val

[V]
[V]
[V]
[V]

GCT
GCC
GCA
GCG

Ala
Ala
Ala
Ala

[A]
[A]
[A]
[A]

GAT
GAC
GAA
GAG

Asp
Asp
Glu
Glu

[D]
[D]
[E]
[E]

GGT
GGC
GGA
GGG

Gly
Gly
Gly
Gly

[G]
[G]
[G]
[G]

T
C
A
G

Codon usage

All but 2 amino acids (W and M) are coded by more

than one codon.
S is coded by 6 different codons.
Different organisms often prefers one particular
codon to encode a particular amino acid.
For S. pombe, C. elegans, D. melanogaster, and
many unicellular organisms,

highly expressed genes, such as those encoding ribosomal

proteins, have biased patterns of codon usage.
People expected that such biase is to enhance the efficiency
of translation.

More on Gene Structure

regulatory region 5' untranslated region

coding region

3' untranslated region

Gene has 4 regions

Coding region contains the codons for protein. It

is also called open reading frame. Its length is a
multiple of 3. It must begin with start codon, end
with end codon, and the rest of its codons are not
a end codon.
mRNA transcript contains 5 untranslated region +
coding region + 3 untranslated region
Regulatory region contains promoter, which
regulate the transcription process.

The translation process

The translation process is handled by a

molecular complex ribosome which consists
of both proteins and ribosomal RNA (rRNA)
1.

2.

3.

Ribosome read mRNA and the translation starts

around start codon (translation start site)
With the help of tRNA, each codon is translated to
an amino acid
The translation stop once ribosome read the stop
codon (translation stop site)

More on tRNA

tRNA --- transfer RNA

There are 61 different
tRNAs, each correspond to
a nontermination codon
Each tRNA folds to form a
cloverleaf-shaped structure

One side holds an anticodon

The other side holds the
appropiate amino acid

Central Dogma for Eucaryotes

Transcription is done
within nucleus
Translation is done
outside nucleus

DNA
transcription
Add 5 cap and
poly A tail
AAAAA

RNA splicing
AAAAA

nucleus

export
AAAAA

translation
modification
cytoplasm

Introns and exons

Eukaryotic genes contain introns and exons.

Introns are sequences that ultimately will be spliced out of

the mRNA
Introns normally satisfies the GT-AG rule, that is, intron
begins with GT and end with AG.
Each gene can have many introns and each intron may has
thousands bases.

Introns can be very long. An extreme example (gene

that associated with the disease cystic fibrosis in
humans):

With 24 introns of total length 1M

The total length of exons 1k

Transcription (Eukaryotes)
1.

2.

3.

4.

Transcription produces the

pre-mRNA which contains
both introns and exons
5 cap and poly-A tail are
added to pre-mRNA
RNA splicing removes the
introns and mRNA is produced.
mRNA are transported out of
the nucleus

DNA
transcription
Add 5 cap and
poly A tail
AAAAA

RNA splicing
AAAAA

nucleus

export

Gene structure (Eukaryotes)

promoter

exon 1

intron

exon 2

intron

exon 3

splicing
exon 1

exon 2

exon 3

translate the
yellow part as protein

The length
of the yellow part
must be multiple of 3!

Post-translation modification
(PTM)

Post-translation modification is the chemical

modification of a protein after its translation.
It involves

Addition of functional groups

Addition of other peptides

E.g acylation, methylation, phosphorylation

E.g. ubiquitination, the covalent linkage to the protein
ubiquitin.

Structural changes

E.g. disulfide bridges, the covalent linkage of two

cysteine amino acids.

Examples of PTM (Kinase and

Phosphatases)

Phosphorylation is a process to add a phosphate

(PO4) group to a protein.
Kinase and Phosphatases can phosphorylate and
dephosphorylate a protein.
This process changes the conformation of proteins
and causes them to become activated or deactivated.

For example, phosphorylation of p53 (tumor

suppressor protein) causes apoptotic cell death.

Phosphorylation is used to dynamically turn on or off

many signaling pathways.

Example of PTM (tRNA)

Aminoacylation is the process of adding

an aminoacyl group to a protein.
tRNA applies aminoacylation to
covalently link its 3 end CCA to an
amino acid.
This process is known as an aminoacyl
tRNA synthetase.

Population genetic

Given the genome of two individuals of the same

species, if there exists a position (called loci) where
the single nucleotides between the two individuals
are different, we call it a single nucleotide
polymorphism (SNP).
For human, we expect SNPs are responsible for over
80% of the variation between two individuals.
Hence, understanding SNPs can help us to
understand the different within a population.
For example, in human, SNPs control the color of
hair, the blood type, etc of different individual. Also,
many diseases like cancer are related to SNPs.

Basic Biotechnological Tools

Cutting and breaking DNA

Copying DNA

Restriction Enzymes
Shortgun method
Cloning
Polymerase Chain Reaction PCR

Measuring length of DNA

Gel Electrophoresis

Restriction Enzymes

Restriction enzyme recognizes certain point, called

restriction site, in the DNA with a particular pattern
and break it. Such process is called digestion.
Naturally, restriction enzymes are used to break
foreign DNA to avoid infection.
Example:

EcoRI is the first restriction enzyme discovered that cuts

DNA wherever the sequence GAATTC is found.
Similar to most of the other restriction enzymes, GAATTC is
a palindrome, that is, GAATTC is its own reverse
complement.

Currently, more than 300 known restriction enzymes

have been discovered.

EcoRI

EcoRI is the first discovered restriction

enzyme.
5-GAATTC-3
3-CTTAAG-5

Digested
by EcoRI

5-G
AATTC-3
+
3-CTTAA
G-5

It cut between G and A. Sticky ends are

created.
Note that some restriction enzymes give
rise to blunt ends instead of sticky ends.

Shotgun method

Break the DNA molecule into small

pieces randomly
Method:

Have a solution having a large amount of

purified DNA
By applying high vibration, each molecule
is broken randomly into small fragments.

Cloning

For many experiments, small amounts

of DNAs are not enough.
Cloning is one way to replicate DNAs.

Cloning by plasmid vector

Given a piece of DNA X, the cloning process is as

follows.
1.

2.
3.

Insert X into a plasmid vector with antibiotic-resistance

gene and a recombinant DNA molecule is formed
Insert the recombinant into the host cell (usually, E. coli).
Grow the host cells in the presence of antibiotic.

4.
5.

Note that only cells with antibiotic-resistance gene can grow

When we duplicate the host cell, X is also duplicated.

Select those cells with antibiotic-resistance genes.

Kill them and extract X

Note: cloning requires several days.

Step 1

Step 2

Step 3

Step 4&5

More on cloning

Cloning using plasmid vector is easy to

manipulate in the laboratory. However,
it can only replicate short DNA
fragments (< 25k)
To replicate long DNA fragments (10k100k), we can use yeast vector.

Polymerase Chain Reaction

(PCR)

PCR is invented by Kary B. Mullis in 1984

PCR allows rapidly replication of a selected region of
a DNA without the need for a living cell.

Automated! Time required: a few hours

Inputs for PCR:

Two oligonucleotides are synthesized, each complementary

to the two ends of the region. They are used as primers.
Thermostable DNA polymerase TaqI

Taq stands for the bacterium Thermos aquaticus that grows in

the yellowstone hot springs.

Polymerase Chain Reaction

(PCR)

PCR consists of repeating a cycle with three phases

25-30 times. Each cycle takes about 5 minutes

Phase 1: separate double stranded DNA by heat

Phase 2: cool; add synthesis primers
Phase 3: Add DNA polymerase TaqI to catalyze 5 to 3 DNA
synthesis

Then, the selected region has been amplified

exponentially.

Heat to separate the strands; add primers

Phases 1 & 2

Cycle 1

Replicate the strands using polymerase Taq

Phase 3

Heat to separate the strands; add primers

Phases 1 & 2

Cycle 2

Replicate the strands using polymerase Taq

Phase 3

Repeat this process for about 30 cycles

Then, we have 230 = 1.07x109 molecules.

Example applications of PCR

PCR method is used to amplify DNA

segments to the point where it can be
readily isolated for use.
Example applications:

Clone DNA fragments from mummies

Detection of viral infections

Gel electrophoresis

Developed by Frederick Sanger in 1977

A technique used to separate a mixture of
DNA fragments of different lengths.
We apply an electrical field to the mixture of
DNA.
Note that DNA is negative charged. Due to
friction, small molecules travel faster than
large molecules.
The mixture is separated into bands, each
containing DNA molecules of the same length.

Applications

Separating DNA sequences from a

mixture

For example, after a genome is digested by

a restriction enzyme, hundreds or
thousands of DNA fragments are yielded.
By Gel Electrophoresis, the fragments can
be separated.

Sequence Reconstruction

See next slide

Sequencing by Gel
electrophoresis

An application of gel electrophoresis is to

reconstruct DNA sequence of length 500-800
within a few hours
Idea:

Generating all sequences end with A

Using gel electrophoresis, the sequences end with
A are separated into different bands. Such
information tells us the positions of As in the
sequence.
Similar for C, G, and T

Read the sequence

We have four groups of fragments: A, C, G, and T.

All fragments are placed in negative end.
The fragments move to the positive end.
From the relative distances of the fragments, we can
reconstruct the sequence.
The sequence is TGTACAACT
TCAACATGT

Hybridization

Among thousands of DNA fragments, Biologists

routinely need to find a DNA fragment which
contains a particular DNA subsequence.
This can be done based on hybridization.
1.

2.

3.
4.

Suppose we need to find a DNA fragments which contains

ACCGAT.
Create probes which is inversely complementary to
ACCGAT.
Mix the probes with the DNA fragments.
Due to the hybridization rule (A=T, CG), DNA fragments
which contain ACCGAT will hybridize with the probes.

DNA array

The idea of hybridization leads to the DNA

array technology.
In the past, one gene in one experiment
Hard to get the whole picture
DNA array is a technology which allows
researchers to do experiment on a set of
genes or even the whole genome.

DNA arrays idea (I)

An orderly arrangement of thousands of

spots.
Each spot contains many copies of the
same DNA fragment.

DNA arrays idea (II)

When the array is exposed to the target solution,

DNA fragments in both array and target solution will
match based on hybridization rule:

A=T, CG (hydrogen bond)

Such idea allows us to do thousands of hybridization

experiments at the same time.

DNA sample

hybridize

Applications of DNA arrays

Sequencing by hybridization

Expression profile of a cell

DNA arrays allow us to monitor the activities within a cell

Each spot contains the complement of a particular gene
Due to hybridization, we can measure the concentration of
different mRNAs within a cell

SNP detection

A promising alternative to sequencing by gel electrophoresis

It may be able to reconstruct longer DNA sequences in
shorter time

Using probes with different alleles to detect the single

nucleotide variation.

Many many other applications!

More advance tools

Mass Spectrometry
SAGE, PET technology

History of bioinformatics (I)

1866: Gregor Mendel discover genetics

Mendels experiments on peas unveil some

biological elements called genes which pass
information from generation to generation
At that time, people think genetic information is
carried by some chromosomal protein

1869: DNA was discovered

1944: Avery and McCarty demonstrate DNA is
the major carrier of genetic information
1953: James Watson and Francis Crick
deduced the three dimensional structure of
DNA

History of bioinformatics (II)

1961: Elucidation of the genetic code, mapping DNA

to peptides (proteins) [Marshall Nirenberg]
1968: Discovery of Restriction Enzyme
1970s: Development of DNA sequencing techniques:
sequence segmentation and electrophoresis
1985: Development of Polymerase-Chain-Reaction
(PCR): By exploiting natural replication, amplify DNA
samples so that they are enough for doing
experiment
1986: Discovery of RNA Splicing

History of bioinformatics (III)

1980-1990: Complete sequencing of the genomes of various

organisms
1990: Launch of Human Genome Project (HGP)
1998: The discovery of post-transcription control called RNA
interference [Fire and Mello]
2000: By shotgun sequencing, Craig Venter and Francis Collins
jointly announced the publication of the first draft of the human
genome.
In the future 10 to 20 years:

Genomes to Life (GTL) Project

ENCODE Project

Understanding the detail mechanism of the cell

Annotating the whole genome

HAPMAP Project

Studying the variation of DNA for individuals