General Introduction to the Genome

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General Introduction to the Genome
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An Outlines

• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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Molecular Biology Major Events
1869
Johann Friedrich
DNA Discovery
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Molecular Biology Major Events
Edward Tatum
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The Central Dogma
Target
Book
Book shelves
Nucleus
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What is Life made of?
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Eukaryotes vs Prokaryotes
DNA
DNA
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Prokaryotes Eukaryotes
Single cell Single or multi cell
No nucleus Nucleus
No organelles Organelles
One piece of circular DNA Chromosomes
No mRNA post transcriptional modification Exons/Introns splicing
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The Cell Chemical Composition

• 70 Water
• 7 Small molecules
• Salts
• Amino acids? (Protein)
• Nucleotides? (DNA, RAN)
• 23 macromolecules
• Proteins
• Polysaccharides
• Lipids

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The Cell The 3 Critical Molecules
Form enzymes Form bodys components
Hold Genetic information
Transfer Information Synthesize Protein
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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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DNA the Nucleotide
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DNA Nitrogenous base
Purines
Pyrimidines
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DNA Polymerization reaction
5 P
3OH
5
3
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DNA hydrogn bounds
No of base pairs Genome Size HG 3200 Mbp (Mb)
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Sugar- Phosphate Back bone
DNA Watson - Crick Model 1951
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DNA Watson - Crick Model
Sugar- Phosphate Back bone
No of base pairs Genome Size HG 3200 Mbp (Mb)
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RNA versus DNA
G, A ,C,T
G, A ,C,U
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Protein structure

• 1902 - Emil Hermann Fischer wins Nobel prize
  showed amino acids are linked and form proteins

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Amino acid Basic unit of protein
Different side chains, R, determine the
properties of 20 amino acids.
Amino group
Carboxylic acid group
An amino acid
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Protein structure

• Primary structure
• Secondary structure
• Super-secondary structure
• Tertiary structure
• Quaternary structure

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Protein Structure Predication Problem
Protein sequence
Protein 3D structure
Protein Function
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The Central DogmaGenes is proteins blueprint,
Genome
DNA
Gene
Protein
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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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Protein Synthesis DNA, RNA, and the Flow of
Information
Replication
Translation
Transcription
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Protein Synthesis Gene Expression
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mRNA
Gene 3
1
Gene 2
2
3
Gene 1
Splicing
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Alternative Splicing
Pre-mRNA
mRNA
Gene 3
1
Gene 2
3
2
Gene 1
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m-RNA Editing
Pre-mRNA
mRNA
Gene 3
1
Gene 2
2
3
Gene 1
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Translation
Pre-mRNA
Start Codon
mRNA
Gene 3
AUGAUAAC UA G
Gene 2
CV
Gene 1
Stop Codon
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Protein Synthesis The Genetic Code
Start
Stop
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Gene Regulation
1
Gene 1
2
3
R Gene 1
Regulatory protein
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Gene Regulation
We have a little knowledge about regulatory
mechanisms
Regulatory protein Gene 1
Gene 2
Gene 1
Regulatory protein Gene 2
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What a big Genome Size?

• The 12 font size enables approximately 60
  nucleotides of DNA sequence to be written in a
  line 10 cm in length.
• Genome size total number of nucleotide base
  pairs.
• typically in millions of base pairs, or megabases
  abbreviated Mb or Mbp)

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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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the human genome sequence would stretch for 5000
km, the distance from Montreal to London, Los
Angeles to Panama, Tokyo to Calcutta, Cape Town
to Addis Ababa, or Auckland to Perth
The sequence would fill about 3000 books the size
of book 600 pages size.
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Genome size of organism are different
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Genome size is not good indicator for genes number
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• Space is saved in the genomes of less complex
  organisms because the genes are more closely
  packed together.

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C-value paradox

• Correlation between the complexity of an
  organism and the size of its genome was looked on
  as a bit of a puzzle.

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Genome Anatomy
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Human Genome Anatomy
Human genome? Nuclear genome
? Mitochondrial genome
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Human Mitochondrial Genome Anatomy

• it is much smaller than the nuclear genome(17
  kB), and it contains just 37 genes.
• 13 code proteins and 24 specify non-coding RNA.
• do not contain intron.
• is typical of the mitochondrial genomes of other
  animals

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Nuclear Human Genome Anatomy
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Nuclear Human Genome Anatomy Protein Coding Genes
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Nuclear Human Genome Anatomy Protein Coding Genes
five exons, separated by four introns.
average exons nine exons per gene
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Two gene segments (V28 and V29-1)
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Nuclear Human Genome Anatomy pseudogene
Non functional genes
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Nuclear Human Genome Anatomy genome-wide repeat

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Nuclear Human Genome Anatomy genome-wide
repeat

• Tandemly repeated DNA
• Minisatellite DNA
• Microsatellite DNA
• Interspersed genome-wide repeats
• SINE
• LINES
• LTR
• DNA transposons

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Nuclear Human Genome Anatomy genome-wide repeat
Minisatellite DNA

• we are familiar with because of its association
  with structural features of chromosomes.
• Telomeric DNA, which in humans comprises hundreds
  of copies of the motif 5'-TTAGGG-3'.

..
TTAGGG
TTAGGG
TTAGGG
..
AATCCC
AATCCC
AATCCC
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The content of the human nuclear genome
genome-wide repeat Microsatellite DNA

• microsatellites with a CA repeat, such as
• make up 0.25 of the genome, 8 Mb in all.
• Single base-pair repeats such as
• make up another 0.15.

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Nuclear Human Genome Anatomy genome-wide repeat
Interspersed repeat
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Gene Classification Gene function

• This system has the advantage that the fairly
  broad functional categories used in can be
  further subdivided to produce a hierarchy of
  increasingly specific functional descriptions for
  smaller and smaller sets of genes.
• The weakness
• functions have not yet been
  assigned to many eukaryotic genes.

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Gene Classification Gene function

• The gene catalog couldnt tell us why we are
  human?
• it may still not be possible simply from genome
  comparisons with the chimpanzee genome to
  determine what makes us human

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Gene Classification Gene function

• The major categories of protein coding genes
  represent the most studied areas of cell biology,
  which means that many of the relevant genes can
  be recognized because their protein products are
  known.
• Genes whose products have not yet been identified
  are more likely to be involved in the less well
  studied areas of cellular activity.

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Gene classification Protein Domain

• A more powerful method is to base the
  classification not on the functions of genes but
  on the structures of the proteins that they
  specify.
• A protein molecule is constructed from a series
  of domains, each of which has a particular
  biochemical function.

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Gene classification Protein Domain
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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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What is Bioinformatics?

• Integration of computational and biological
  methods
• to convert biological information into general
  theories.

aatgcatgcggctatgctaatgcatgcggctatgctaagctgggatccg
atgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggat
ccgatgactatgctaagctgggatccgatgacaatgcatgcggctatgct
aatgaatggtcttgggatttaccttggaatgctaagctgggatccgatga
caatgcatgcggctatgctaatgaatggtcttgggatttaccttggaata
tgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcg
gctatgctaatgcatgcggctatgcaagctgggatccgatgactatgcta
agctgcggctatgctaatgcatgcggctatgctaagctgggatccgatga
caatgcatgcggctatgctaatgcatgcggctatgcaagctgggatcctg
cggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgg
gatccgatgacaatgcatgcggctatgctaatgaatggtcttgggattta
ccttggaatatgctaatgcatgcggctatgctaagctgggaatgcatgcg
gctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgca
tgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgc
taatgcatgcggctatgctaagctcatgcggctatgctaagctgggaatg
catgcggctatgctaagctgggatccgatgacaatgcatgcggctatgct
aatgcatgcggctatgcaagctgggatccgatgactatgctaagctgcgg
ctatgctaatgcatgcggctatgctaagctcggctatgctaatgaatggt
cttgggatttaccttggaatgctaagctgggatccgatgacaatgcatgc
ggctatgctaatgaatggtcttgggatttaccttggaatatgctaatgca
tgcggctatgctaagctgggaatgcatgcggctatgctaagctgggatcc
gatgacaatgcatgcggctatgctaatgcatgcggctatgcaagctggga
tccgatgactatgctaagctgcggctatgctaatgcatgcggctatgcta
agctcatgcgg
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Data structures Software engineering (C,
C,PERL)
Cell structure Genome, genes DNA, RNA
Biology
Computer Science
Bioinformatics
Chemistry
Statistics
Markof Model Neural Network
Protein structure Molecular bounds
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Bioinformatics Subareas

• The subareas within bioinformatics include
  Genomics and Proteomics.

Genome comparison evolutionary tree
Microarray Analysis Gene predication Gene
classification Gene regulation
Protein 3D predication Protein protein
interaction Protein alignment
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• Molecular Biology Major Events
• DNA, RNA
• Protein Synthesis(Transcription Translation)
• Genome Anatomy
• Bioinformatics
• Genomics Signal Processing

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What is GSP?

• Analysis

• Using Theory and Methods of Signal Processing

• Processing

aatgcatgcggctatgctaatgcatgcggctatgctaagctgggatccg
atgacaatgcatgcggctatgctaatgcatgcggctatgcaagctgggat
ccgatgactatgctaagctgggatccgatgacaatgcatgcggctatgct
aatgaatggtcttgggatttaccttggaatgctaagctgggatccgatga
caatgcatgcggctatgctaatgaatggtcttgggatttaccttggaata
tgctaatgcatgcggctatgctaagctgggatccgatgacaatgcatgcg
gctatgctaatgcatgcggctatgcaagctgggatccgatgactatgcta
agctgcggctatgctaatgcatgcggctatgctaagctgggatccgatga
caatgcatgcggctatgctaatgcatgcggctatgcaagctgggatcctg
cggctatgctaatgaatggtcttgggatttaccttggaatgctaagctgg
gatccgatgacaatgcatgcggctatgctaatgaatggtcttgggattta
ccttggaatatgctaatgcatgcggctatgctaagctgggaatgcatgcg
gctatgctaagctgggatccgatgacaatgcatgcggctatgctaatgca
tgcggctatgcaagctgggatccgatgactatgctaagctgcggctatgc
taatgcatgcggctatgctaagctcatgcggctatgctaagctgg

• To gain global understanding of Genome.

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GSP Labs

• The Genomic Signal
• Processing Laboratory at Texas AM
  University.
• The Computational Biology Division of the
  Translational Genomics
• Research Institute in Phoenix, Arizona.

To model Genomic Regulatory Mechanisms for the
purposes of diagnosis and therapy.
Edward R. Dougherty
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GSP Labs

• Columbia's Genomic Information Systems Laboratory
  
• at Columbia University

Dimitris Anastassiou
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GSP Labs

• DSP Group, Department of Electrical Engineering,
  California Institute of Technology

P. P. Vaidyanathan
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Mapping Character String to Numerical Sequences
AAAATTTTCCCGGGTAGCTTTCCCGGGT
0001110101010101111111111000
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Research Area of GSP

• Gene Predication
• Genes Predication
• Hidden Markov Models (HMM)
• Fourier Transform
• Wavelet Transform
• Resonant Recognition Model (RRM)
• To identify the common hot spots of many protein
  molecules using Fourier transform methods.

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References

• http//biology.ucok.edu/bidlack/biology/notes.htm
• http//www.ncbi.nlm.nih.gov/books/bv.fcgi?ridgeno
  mes
• http//www.estrellamountain.edu/faculty/farabee/bi
  obk/biobooktoc.html
• http//www.werathah.com/
• http//lectures.molgen.mpg.de/online_lectures.html
  

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References

• http//www.biology.lsu.edu/webfac/jmoroney/BIOL309
  0/

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