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.

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.

Dictyostelium discoideum (social amoeba/ slime mould)

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

Caenorhabditis elegans (nematode round worm),

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.

Drosophila melanogaster (fruit fly)

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.

Danio rerio (zebrafish)

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

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

Gallus gallus (Chick)

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 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

Yeast

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

Slime mould

Relative strengths of Model Organisms

Organism 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

Worm

Relative strengths of Model Organisms

Organism Advantages Limitations

Fly

Excellent genetics Embryological manipulations difficult Genome sequenced 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 Advantages Limitations

Zebra fish

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 Advantages Limitations

Arabidopis

Universal model plant Small size Relatively short life cycle Small, sequenced genome Transformed easily Transgenics

Embryological manipulations non trivial

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 Advantages Limitations

Frog

Relative strengths of Model Organisms

Organism Advantages Limitations

Chick

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 Limitations

Mouse

Mammals 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