Model Organisms
Aurnab Ghose; 150107
What are Model Organisms?
A model organism is a species that has been
widely studied, usually because it has particular
experimental advantages, and it is expected that
discoveries made in the model organism will
provide insight into workings of other organisms
What makes Model Organisms possible?
Common ancestry of all organisms resulting
conservation of major aspects of biology
Typical considerations while selecting Model Organisms
Rapid development with short life cycles
Small adult size
Ready availability and inexpensive maintenance
and breeding
Tractability to experimental methodology
Become even more useful when many other
scientists work on them
Biology being studied have relevance to humans
History of Model Organisms
Some of the earliest work was done by Mendel
that led to the discovery of genetics
The first extensively studied modern model
organism was the fly
Major types of Model Organisms
Genetic Model Organisms
- amenable to genetic analysis
- breed quickly in large numbers allowing large
scale crosses followed over generations
- many mutants available and detailed genetic
maps can be created
- e.g., Baker's yeast (Saccharomyces cerevisiae)
Fruit fly (Drosophila melanogaster)
Nematode worm (Caenorhabditis elegans)
Major types of Model Organisms
Experimental Model Organisms
- not so suitable for genetic analysis
- other characteristics making them invaluable to
research
- e.g., African clawed toad (Xenopus laevis) &
Chick (Gallus gallus) have robust embryos
that can be studied and manipulated with
ease. Widely used in developmental biology
Major types of Model Organisms
Genomic Model Organisms
- become important as they occupy special places
in the evolutionary tree or their genomes possess
some unique, advantageous quality
- Puffer fish (Fugu rubripes) have similar gene
repertoire to humans but a much smaller genome
(400 million base pairs instead of 3000 million)
Saccharomyces cerevisiae
(baker's or brewer's yeast)
Simple eukaryotic organisms but many essential cellular
processes are conserved between yeast and humans
The complete genome sequence obtained in the spring of 1996,
making yeast the first eukaryotic organism to be completely
sequenced
Approx. 20% human disease genes have yeast homologues
Ease of genetic manipulation of yeast allows its use for
conveniently analyzing and functionally dissecting gene products
from other eukaryotes.
Dictyostelium discoideum
(social amoeba/ slime mould)
Rapid generation time, reverse genetics and its ease of
use in the study of many areas of cell and molecular
biology
Cells grow as unicellular organisms but, upon starvation,
aggregate to form a multicellular tissue capable of
differentiating into multiple cell types.
Because the life cycle consists of both unicellular and
multicellular phases, Dictyostelium provides insight into
processes needed for multicellularity.
Caenorhabditis elegans
(nematode round worm),
One of the best characterized multicellular animal at the level of
genomics, genetics, embryology
Its genome is fully sequenced
C. elegans is unique in that it can be grown and genetically
manipulated with the speed and ease of a micro-organism while
offering the features of a real animal
C. elegans has a full set of organ systems, has complex sensory
systems, shows coordinated behavior, and it is possible to trace the
lineage of every one of its approximately 1000 constituent cells
Drosophila melanogaster
(fruit fly)
The best characterized model system
Easy-to-manipulate genetic system
Relatively low cost
Biological complexity comparable to that of a mammal
Many organ systems in mammals have well-conserved homologues
in Drosophila
Has provided new insights into forms of cancer, neurodegenerative
diseases, behavior, immunity, aging, multigenic inheritance, and
development.
Danio rerio (zebrafish)
Small size, short life cycle, ease of culture, and ability to readily
produce mutations relevant to human health and disease
The embryonic development can be seen through its transparent
egg and closely resembles that of higher vertebrates
Other shared features with humans include blood, kidney, and
optical systems
In addition, its genome is half the size of the mouse and human
genomes, which is valuable in identification of key vertebrate genes.
Arabidopsis thaliana
(thale cress)
Small flowering plant
Has a small genome relative to other plants and is easily
grown under laboratory conditions
Amenable to some genetics particularly generation of
transgenics
Allows insight into numerous features of plant biology,
including those of significant value to agriculture, energy,
environment, and human health
Xenopus laevis
(African clawed toad)
Produce large number of large eggs
Embryos large, robust, development occurs outside the
body
Accessibility of embryos allows pharmacological studies,
grafting, treatment with proteins, etc.
Possible to produce transgenics
Great insight into development
Gallus gallus
(Chick)
Easily obtainable large eggs
Embryos large, robust, development occurs outside the body
Accessibility of embryos allows pharmacological studies,
grafting, treatment with proteins, etc.
Possible to produce transgenics
Great insight into development
Mus musculus
(mouse)
Closest mammalian model organism to humans
Genes that code for proteins responsible for carrying out vital
biological processes in both the human and the mouse share a
high degree of similarity.
Therefore, the mouse has already proven extremely useful in
development, genetic, and immunology studies
Transgenics and KO s possible
A great system for studying and understanding human disease,
as well as a mechanism for investigating new treatment
strategies in ways that cannot be done in humans
The best model of a cat is another, or preferably the
same cat.
Norbert Weiner
Relative strengths of Model Organisms
Organism
Yeast
Slime
mould
Advantages
Limitations
Excellent genetics
Unicellular
Powerful second site screening
No distinct tissues
Powerful molecular techniques
Genes can be easily cloned
Genome sequence complete
Possess all basic eukaryotic cell organelles
Cell cycle control similar to animals
Excellent genetics
Limited cellular diversity
Powerful second site screening
Powerful molecular techniques
Genes can be easily cloned
Genome sequenced
Simple cellular behaviors similar to animals
Motility
Chemotaxis
Relative strengths of Model Organisms
Organism
Worm
Advantages
Limitations
Excellent genetics
Limited external morphology
Hermaphrodites/self-fertilization Less similar to human
Fast generation times
Detailed analysis of gene
expression patterns difficult
Second site screens
Embryological manipulations
difficult
Powerful molecular techniques
Genes can be easily cloned
RNAi effective
Genome sequence complete
Few cells: 959 cells
Morphology fully characterized
All cell lineages known
Laser ablation of single identified cells
Relative strengths of Model Organisms
Organism
Advantages
Excellent genetics
Genome sequenced
Fly
Limitations
Embryological manipulations difficult
Targeted gene disruption still difficult,
although possible
RNAi effective
Fast generation time
Second site suppressor/enhancer screens
Powerful molecular techniques
Genes can be easily cloned
Transgenic animals easily generated
Targeted misexpression of genes in space and time
Mosaic analysis: determine where gene acts
Laser ablation of single cells possible
Relative strengths of Model Organisms
Organism
Zebra
fish
Advantages
Limitations
Simplest vertebrate
Not yet trivial to clone genes
Good genetics
Transgenics not trivial
Transparent embryos
No targeted gene disruption
Embryo manipulations possible
Organ systems similar to other
vertebrates (e.g., eyes, heart, blood,
gastrointestinal tract)
Rapid vertebrate development
Relative strengths of Model Organisms
Organism
Arabidopis
Advantages
Universal model plant
Small size
Relatively short life cycle
Small, sequenced genome
Transformed easily
Transgenics
Limitations
Embryological manipulations
non trivial
Relative strengths of Model Organisms
Organism
Frog
Advantages
Limitations
A vertebrate
Limited genetics
Robust embryos
Genome tetraploid (X. laevis)
Ectopic gene expression in embryos
Accessibility of embryo
Genome unsequenced
Excellent experimental embryology
(X. laevis)
Transgenesis difficult
In vitro cultures
Injection of RNA into identifiable blastomeres
Relative strengths of Model Organisms
Organism
Chick
Advantages
Limitations
Availability, low cost
Limited genetics
Accessibility, outside of mother
Genome sequenced
Great for embryological manipulation;
transplants of tissue
Easily transfected by avian retroviruses
Relative strengths of Model Organisms
Organism
Advantages
Mammals
Mouse
Limitations
Classic forward genetics
difficult
Organs homologous to human
Early-acting mutant phenotypes
difficult to study (resorbed by
mother)
Reverse genetics: targeted KOs Embryonic manipulations
difficult (inside mother)
Developmental overview
Development and life cycle slow
same as for all mammals
Large mutant collection
Construction of chimeric embryos possible
Availability of material at all stages
Source of primary cells for culture
