2. What are model organisms?
A model organism is a species that has been widely studied, usually because it is
easy to maintain and breed in a laboratory setting and has particular
experimental advantages.
These are non-human species that are used in the laboratory
to help scientists understand biological processes.
They are usually organisms that are easy to maintain and
breed in a laboratory setting.
They may have particularly robust embryos that are easily
studied and manipulated in the lab, this is useful for
scientists studying development.
Or they may occupy a pivotal position in the evolutionary
tree, this is useful for scientists studying evolution.
3. Genome projects and model organisms
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
4. Genome projects
Completed genomes:
Eubacteria (inc. Escherichia coli, Bacillis subtilis,
Haemophilus influenzae, Synechocystis PCC6803)
Archaea (inc. Methanococcus jannaschii,
Methanobacterium thermoautotrophium)
Eukarya:
Saccharomyces cerevisiae
Caenorhabditis elegans
Homo sapiens
Arabidopsis thaliana
Partially sequenced genomes e.g. Drosophila
melanogaster, Fugu rubripes, Oryza sativa
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
5. Relationships between model organisms
H. sapiens
C. elegans
D. melanogaster
S. cerevisiae
A. thaliana
Methanococcus
Archaeglobus
Synechocystis PCC6803
B. subtilis
M. genitalium
M. pneumoniae
B. burgdorferi
H. influenzae
E. coli
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
6. Eubacterial genomes: E. coli
4288 protein coding genes:
Average ORF 317 amino acids
Very compact: average distance
between genes 118bp
Numerous paralogous gene families:
38 – 45% of genes arisen through
duplication
Homologues:
H. influenzae (1130 of 1703)
Synechocystis (675 of 3168)
M. jannaschii (231 of 1738)
S. cerevisiae (254 of 5885)
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
7. The minimum genome and redundancy
Minimum set of genes required for survival:
Replication and transcription
Translation (rRNA, ribosomal proteins, tRNAs etc.)
Transport proteins to derive nutrients
ATP synthesis
Entire pathways eliminated in Mycoplasma:
Amino acid biosynthesis (1 gene vs. 68 in H. influenzae)
Metabolism (44 genes vs. 228 in H. influenzae)
Comparison of M. genitalium and H. influenzae has
identified a minimum set of 256 genes
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
8. Fungal genomes: S. cerevisiae
First completely sequenced
eukaryote genome
Very compact genome:
Short intergenic regions
Scarcity of introns
Lack of repetitive sequences
Strong evidence of duplication:
Chromosome segments
Single genes
Redundancy: non-essential genes
provide selective advantage
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
9. Invertebrate genomes: C. elegans
Genome even less compact than yeast:
One gene every 7143 bp (2155 bp in
yeast)
Due mainly to introns in protein coding
genes
Much more compact than humans (One
gene every 50,000 bp)
Compactness due mainly to
polycistronic arrangement:
Trans-splicing
Co-expression and co-regulation
Source (Slide Share): Genome projects and model organisms,
Level 3 Molecular Evolution and Bioinformatics by Jim Provan
10. Mice as a Model Organism
The mouse is closely related to humans with a striking similarity to us in
terms of anatomy, physiology and genetics. This makes the mouse an
extremely useful model organism.
The sequence of the mouse genome was published in 2002. When compared
with the human genome it was found that the two genomes were of similar
size and almost every gene in the human genome has a counterpart in the
mouse.
So, the researchers have been able to develop thousands of mouse strains
with mutations that mirror those seen in human genetic disease
11. History of Mice in science
In 1902, French biologist Lucien Cuénot was the first to demonstrate
Mendel’s theories of inheritance by highlighting the genetics of coat colour
characteristics in mice.
In Harvard, William Castle began his research in the same year, buying mice
from a local mouse enthusiast. Together with his student Clarence Little,
Castle produced a series of important papers on the genetics of coat colour
in mice.
It took Clarence four years between 1909 and 1913 to create a healthy and
genetically stable inbred strain.
12. Transgenic Mice
Transgenic mice are mice that contain additional, artificially introduced
genetic material in every cell.
This additional genetic material either results in a gain or loss of function of a
certain gene.
For example, this may mean the mouse starts to produce a new protein.
This allows scientists to investigate what specific genes do in the body.
13. Knockout Mice
Knockout mice are the result of the inactivation of a specific gene. The
resulting change in the appearance, behaviour or biochemical
characteristics of the mouse then gives an indication of the gene’s normal
role in the mouse, and perhaps in humans.
Knockout mice are produced by a technique called ‘gene targeting’. This
involves ‘knocking out’ a gene sequence from the mouse genome and
inserting an artificial gene sequence that has been generated in the lab.
14. Knockout Mice
As with transgenic mice, gene targeting is carried out in mouse embryonic
stem cells (ES cells) derived from a very early (usually male) mouse embryo.
By manipulating the cells at this early stage of development, scientists aim to
get the modified ES cells to contribute to the germ line, and give rise to
sperm.
This way the sperm can then carry the mutation and fertilise a normal egg to
carry on the knocked-out genome on to the next generation.
More than 4,000 genes have been ‘knocked-out’ using this method to help
scientists investigate exactly what each gene’s role is in the body.
15. Sequencing the Mice genome
Before the sequenced genome was available, looking for a gene or a
mutation was like looking for a needle in a haystack.
Sequencing of the mouse genome was completed in 2002, a powerful
scientific tool was made available.
Now, with a huge database of information available online, all that is
needed are a few clicks for researchers to be able to look up specific genes
and their location on the mouse chromosomes.
From this we can then choose one or two areas that look the most
promising to search for a mutation.
16. Significance of Mice genome
Researchers have developed an array of mouse models to help
scientists understand a whole collection of human diseases.
This has been made possible by the ability to create
transgenic and knockout mouse models which give scientists
the means to observe the function of individual genes.
The genetic similarities between mice and men means that
the knowledge derived from experiments with these mice can
provide invaluable insights into human biology.
Being able to go back and forth between the mouse and
human genomes so easily has also made it much simpler and
quicker to target related human genes that could be
candidates for drug development.
Now, discoveries that would once have taken years can now
be done in a matter of months.
17. Drosophila as a Model Organism
The fruit fly (Drosophila melanogaster) has been extensively studied for
over a century as a model organism for genetic investigations.
It also has many characteristics which make it an ideal organism for the
study of animal development and behavior, neurobiology, and human
genetic diseases and conditions
A good model organism needs to share, on the molecular level, many similar
features and pathways with humans.
Approximately 60% of a group of readily identified genes that are mutated,
amplified, or deleted in a diverse set of human diseases have a counterpart
in Drosophila
18. Benefits of Fruit fly
The fruit fly has many practical features that allow scientists to carry out
research with ease:
A short life cycle,
Ease of culture and maintenance, and
Less number of chromosomes
Small genome size (in terms of base pairs), but
Giant salivary gland chromosomes, known as polytene chromosomes.
19. Life Cycle of Drosophila melanogaster
Image Source: Carolina
Biological Supply Company
20. Life Cycle of Drosophila melanogaster
The female fruit fly, about 3 mm in length, will lay between 750 and
1,500 eggs in her lifetime.
The life cycle of the fruit fly only takes about 12 days to complete at
room temperature (25°C).
After the egg (at a mere half a millimeter in length) is fertilized, the
embryo emerges in ~24 hours
21. Genome of Drosophila
As with humans, the chromosomes of Drosophila melanogaster come in pairs --
but unlike humans, which have 23 pairs of chromosomes, the fruit fly has only
four: a pair of sex chromosomes (two X chromosomes for females, one X and
one Y for males), together designated Chromosome 1, along with three pairs of
autosomes (non-sex chromosomes) labeled 2 through 4.
Chromosome 4 is the smallest and is also called the dot chromosome. It
represents just ~2% of the fly genome.
22. The giant polytene chromosomes found in the fly's salivary glands (compared here
with the chromosomes from the fly's ovary) are another characteristic that makes
the fruit fly an important organism for laboratory studies. These easily visualized
chromosomes provided a road map for early geneticists.
Image source: Modified from T. S. Painter, J. Hered. 25, 465-476 (1934)
23. Genome of Drosophila
In terms of base pairs, the fly genome is only around 5% of the size of the
human genome -- that is, 132 million base pairs for the fly, compared with 3.2
billion base pairs for the human.
In terms of the number of genes: The fly has approximately 15,500 genes on its
four chromosomes, whereas humans have about 22,000 genes among their 23
chromosomes. Thus the density of genes per chromosome in Drosophila is higher
than for the human genome.
24. Genome of Drosophila
Humans and flies have retained the same genes from their common ancestor
(known as homologs) over about 60% of their genome.
Based on an initial comparison, approximately 60% of genes associated with
human cancers and other genetic diseases are found in the fly genome.
25. The genome of the
cenancestor
Availability of complete genome sequences from the three domains of
life creates an opportunity for the reconstruction of the complete
genome of the common ancestor:
Of minimal bacterial set (256 genes), 143 have orthologues in yeast
(eukaryote)
Universal translation apparatus suggests that cenancestor had a fully
developed translation system
Extreme differences in DNA replication apparatus
Many fundamental metabolic processes are carried out by similar proteins
in Archaea and eubacteria:
Suggests a universal, autotrophic ancestor
Not all central metabolism is universal (methanogenesis, photosynthesis etc.)