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Transcript
BioInformatics / Computational Biology
Introduction & Biological Terms.
Prepared with lots of help from friends...
Metsada Pasmanik-Chor, Zohar Yakhini
and NUMEROUS WEB RESOURCES.
Outline
• A Few Basic Concepts of Molecular Biology:
• Genetic material - DNA & RNA.
• DNA is a sequence of bases (A,C,T,G).
• Watson-Crick–ery.
•
Proteins.
• The central dogma of molecular biology.
• Bio-Informatics Tools Freely available on
the web: Highlights.
Prokaryotes vs. Eukaryotes
One chromosome,
(sometimes circular).
http://departments.oxy.edu/biology/bio130/lectures_2000/11-13-00_lecture.htm
Cell Size and Shape
10-9 m
All organisms are made of cells - basic unit of life
(1014 cells in the human body; metabolism, replication).
Cells in all organisms have same type ofgenetic material.
The Eukaryotic Cell
cytoskeleton:
* In plants: chloroplast & cell wall.
http://www.biosci.uga.edu/almanac/bio_103/notes/may_15.html
DNA - the Genetic Material
http://www.dnaftb.org/dnaftb/9/concept/index.html
• Each human cell contains
23 pairs of chromosomes.
• Chromosomes can be
distinguished by size and
by unique banding patterns.
• This set is from a male,
since it contains a Y
chromosome.
• Females have two X
chromosomes.
http://www.accessexcellence.org/AE/AEPC/NIH/gene03.html
Different Eukaryotic Cell Types
Different genes are activated in different cells, creating the
specific proteins that give a particular cell type its character.
http://www.accessexcellence.org/AE/AEPC/NIH/gene03.html
Example:
Tissues
in Stomach
• Cells originate from one embrio cell and have identical DNA.
• Different cell types: Metabolism, regulation, function.
http://www.dnaftb.org/dnaftb/17/animation/index.html
DNA Structure
telomere
control region
centromere
gene coding region
•
•
CONTROL REGIONS - Usually are adjacent to genes.
Determine when expressed, to what extend.
“JUNK DNA” - Unknown function.
DNA - (deoxyribonucleic acid THE Double Helix)
Source: Alberts et al
DNA is made of 4 subunits (nucleotides).
Each nucleotide contains: sugar, phosphate group and a base.
A
C
T
G
Nucleotide
Sugar
ribose
(RNA)
deoxyribose
(DNA)
4 DNA bases
Purines
Pyrimidines
Watson-Crick Complementarity
Conclusion: DNA strands are complementary (1953).
Base ratios
% of each base
DNA source
Human
Sheep
Turtle
Sea urchin
Wheat
E. coli
Purines/
Pyrimidines
Pyrimidines
Purines
Watson-Crick Complementarity
A binds to T
C binds to G
AATGCTTAGTC
TTACGAATCAG
AATGCGTAGTC
TTACGAATCAG
Perfect match
One base mismatch
Variability - facts
•
Genes carry the instructions for cellular proteins.
•
Variations in the code is the
source for cellular variations.
•
Disease and susceptibility
to disease can be caused by
changes in the DNA (mutations).
Human
individuality
•
DNA is identical in all cells
of an individual, almost identical
among different individuals of
same species (99.9%), and very
similar in related species (human vs chimpanzee - 98% identity).
•
Only 3% of cellular DNA has a known function !
http://www.brc.dcs.gla.ac.uk/~drg/seminars/bioinformatics/sld032.htm
Hereditary mutations:
Carried in the DNA of the
reproductive cells.
The mutation will be present in
all of the offspring's body cells.
Acquired mutations:
Developed in the DNA during
a person's lifetime.
If the mutation arises in a body cell,
copies of the mutation will exist only
in descendants of that particular cell.
http://www.accessexcellence.org/AE/AEPC/NIH/gene07.html
RNA - ribonucleic acid
Some viruses store genetic
information in form of RNA.
In eukaryotes, RNA is formed
from DNA in a process called
transcription
where elimination of introns
(splicing) occurs
RNA is very similar to DNA but has:
• Only one strand.
• Ribose as a sugar.
• Uracil (U) instead of Thymine (T).
Splicing - RNA Synthesis and Processing
The seven green loops stand for introns
The eight blue bands stand for exons
Chromosomal DNA
Mature
mRNA
Poly A tail
Stop signal
Promoter/enhancer
exons
splicing
Gene
introns
Transcription
by RNA polymerase
exons
mRNA
www.albany.edu/~achm110/ mrna.gif
introns
splicing
Splicing - RNA Synthesis and Processing
http://www1.imim.es/courses/Lisboa01/slide1.5_splicing.html
Example of Alternative Splicing
http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm
Types of RNA
mRNA - A copy of a gene (without introns),
encoding protein sequence.
Used in translation:
tRNA - Small RNA, serves as “adaptor”
between mRNA and amino acids.
rRNA - One of the structural
components of the ribosome
(the translation machine from mRNA to proteins).
http://www.dnaftb.org/dnaftb/24/concept/index.html
See animation at:
http://www.dnaftb.org/dnaftb/21/animation/index.html
Genes can be turned ON and OFF
http://www.dnaftb.org/dnaftb/33/concept/index.html
Transcription Factors
http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm
nitiation of
ranscription by
olymerase
http://www1.imim.es/courses/Lisboa01/slide1.4_transcription.html
Regulation of Expression
promoter
The Genetic Code:
From 43 = 64 Codons to 20 AA.
4 nucleotide types
3 letter code
5’
3’
64 Codons
20 amino
acids
The Genetic Code:
From 43 =
64 Codons
to 20 AA.
http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci5.htm
The Genetic Code
The only start amino acid is Methionine, which has a single codon.
http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci4.htm
Amino Acid Relative FrequenciesMammals
http://cbms.st-and.ac.uk/academics/ryan/Teaching/molbiol/Bioinf_files/v3_document.htm
Nucleotides vs Amino Acids Code
5’
3’
ACGTGTAGTTGCCGTGACG
TGCACATCAACGGCACTGC
3’
5’
A DNA sequence with direction shown
N
PKRGACMLTNQFKRKSACQ
C
A protein sequence with ends indicated
Proteins
Translation -
Mediated by the ribosome,
an organ which is made from
rRNA and proteins.
Proteins are Made of Amino Acids
http://www.iacr.bbsrc.ac.uk/notebook/courses/guide/aa.htm
Translation in Eukaryotes
http://www1.imim.es/courses/Lisboa01/slide1.6_translation.html
Animation: http://cbms.st-and.ac.uk/academics/ryan/Teaching/medsci/Medsci6.htm
Protein Structure
http://www.yangene.com/content22_10.htm
What Determines Cell Structure and Function ?
• Unique protein expression
by each cell type.
• Proteins are ~60% of
dry mass of living cell.
• Proteins determine
function.
How is this
controlled ?
Levels of Eukaryotic Gene Regulation
http://www.library.csi.cuny.edu/~davis/Bioinfo_326/lectures/centralDogmaProteins/centralDogma.html
Central Dogma
Transcription
Translation
mRNA
Gene (DNA)
DNA
RNA
Cells express different subset of the
genes in different tissues and under
different conditions.
Protein
Protein
Symptomes
(Phenotype)
The Central Dogma of Molecular Biology
ReplicationDNA duplication
Nucleus
TranscriptionRNA synthesis
Cytoplasm
TranslationProtein synthesis
http://www.accessexcellence.com/AB/GG/central.html
New Central Dogma…
1 gene
Many mRNA Transcripts
due to alternative splicing
Many protein types
Central Dogma
in the
21st Century.
1 gene
Many mRNA
transcripts
Many protein types
http://www.nature.com/nrg/journal/v3/n1/slideshow/nrg703_bx1.html