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Introduction to molecular biology,
continued
Adding to complexity of the biosphere
* Each multicellular organism has
different kinds of cells with different
gene/protein repertoires
* At least 1.7 million (!) species/organisms,
each with different gene/protein repertoires
Introduction to molecular biology
* DNA molecule as carrier of genetic information
* Gene technology
* Flow of genetic information
* Complexity of the biological world.
* Kingdoms of life - overview of life forms
* Evolution - principles and mechanisms
1
Organisms are remarkably uniform at the molecular level
This uniformity reveals that organisms on Earth have arisen
from a common ancestor
The three kingdoms of life
Eukarya (eukaryotes)
Nucleus. All multicellular organisms , like animals
and plants. Some single-celled organisms like yeast.
Bacteria (eubacteria)
No nucleus. Single-celled. Ubiquitous.
Archaea (archaebacteria)
No nucleus. Single-celled. Certain properties
shared with Eukarya. Live in extreme
environments (like high temperature or high salt)
Bacteria+Archaea are also called prokaryotes
2
Archaea live in extreme environments
3
Tree of life and the three kingdoms of life
Viruses - dependent on living cells for propagation
HIV
4
HIV genome
Introduction to molecular biology
* DNA molecule as carrier of genetic information
* Gene technology
* Flow of genetic information
* Complexity of the biological world.
* Kingdoms of life - overview of life forms
* Evolution - principles and mechanisms
5
Principles of evolution
Reproduction
Variation
Competition/selective pressure
Variation comes from
mutations : changes in base sequence of DNA
1) single nucleotide change (point mutation)
A->T, T->G , etc
2) insertion / deletion of one or several
nucleotides
Such mutations are the result of
Replication errors
Chemicals & irradiation
6
Mutations, cont.
3) Homologous recombination cause large
rearrangements in the genome.
New gene families arise by gene duplication and
divergence
Tree of life and the three kingdoms of life
7
Why do we bother with evolution in bioinformatics?
* We are in experimental biology making use of many model
organisms that are evolutionary related to human
* An extremely common task in bioinformatics is to examine
evolutionary related sequences. (BLAST)
* Comparative genomics can be used to
identify biologically significant
elements
8
Bioinformatics
The application of CS and math in the
handling and analysis of data resulting
from modern gene technology.
Human genome
3 x 109 base pairs
What are the bioinformatics
challenges - what
can we learn from
the sequence?
9
Example 1: Prediction of genes in the human genome
Genome
The complete
genetic
material
of an organism
Gene
a portion of a DNA
molecule that contains all
the information for
production of a protein
10
Example 2 : Bioinformatics aids in predicting the molecular basis
of disease
BRCA1 gene - genetic factor in breast cancer
Cloning and sequencing of the gene revealed a protein remotely
related to a yeast protein (Rad9) involved in cell cycle control
RAD9_YEAST : GNVFDKCIFVLTS-LFENReELRQTIESQGGTVIeSGfstlfnfthplakslvnkgntdn
BRC1_HUMAN : ERVNKRMSMVVSGLTPEEFmLVYKFARKHHITLTnLI-----------------------
RAD9_YEAST : irelalklawkphslfaDCRFACLITKRHLrSLKYLET------LALGWPTLHWKFISAC
BRC1_HUMAN : -----------------TEETTHVVMKTDA-EFVCERTLKyflGIAGGKWVVSYFWVTQS
RAD9_YEAST : IEKKRIVPHLIYQY
BRC1_HUMAN : IKERKMLNEHDFEV
Example 3: Analysis of the human genome reveals a large
number of olfactory receptor proteins
11
Example 4: Sequence analysis is essential
in phylogenetic studies
Human evolution
Origin of man
Closest primate relatives of man?
Did modern humans originate in Africa?
Relationship between human populations
Evolution of viruses / microorganisms that cause human disease
HIV (AIDS)
H5N1 (Bird Flu)
Example 5: Protein structure prediction and structural
bioinformatics is important for our understanding of
biology and is essential in the development of drugs
HIV protease
12