Model organism

Escherichia coli is a model gram-negative prokaryotic organism

Drosophila melanogaster, one of the most famous subjects for experiments

A model organism is a species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms.^[1] In particular, model organisms are widely used to explore potential causes and treatments for human disease when human experimentation would be unfeasible or unethical. This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution.^[2] Studying model organisms can be informative, but care must be taken when generalizing from one organism to another.

Selecting a model organism

Models are those organisms with a wealth of biological data that make them attractive to study as examples for other species – including humans – that are more difficult to study directly. These can be classed as genetic models (with short generation times, such as the fruitfly and nematode worm), experimental models, and genomic models, with a pivotal position in the evolutionary tree ^[3]. Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms.^[4]

Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as short life-cycle, techniques for genetic manipulation (inbred strains, stem cell lines, and methods of transformation) and non-specialist living requirements. Sometimes, the genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion of junk DNA (e.g. yeast, Arabidopsis, or pufferfish).

When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time, accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. As comparative molecular biology has become more common, some researchers have sought model organisms from a wider assortment of lineages on the tree of life.

Use of model organisms

There are many model organisms. One of the first model systems for molecular biology was the bacterium Escherichia coli, a common constituent of the human digestive system. Several of the bacterial viruses (bacteriophage) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4). However, bacteriophages are not organisms because they lack metabolism and depend on functions of the host cells for propagation.

In eukaryotes, several yeasts, particularly Saccharomyces cerevisiae ("baker's" or "budding" yeast), have been widely used in genetics and cell biology, largely because they are quick and easy to grow. The cell cycle in a simple yeast is very similar to the cell cycle in humans and is regulated by homologous proteins. The fruit fly Drosophila melanogaster is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has a polytene (giant) chromosome in its salivary glands that can be examined under a light microscope. The roundworm Caenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities.

Electron microphotograph of tobacco mosaic virus (TMV) particles

Important model organisms

Viruses

Viruses include:

• Phage Lambda
• Phi X 174 - its genome was the first ever to be sequenced. The genome is a circle of 11 genes, 5386 base pairs in length.
• Tobacco mosaic virus

Prokaryotes

Sporulating Bacillus subtilis

Prokaryotes include:

• Escherichia coli (E. coli) - This common, Gram-negative gut bacterium is the most widely-used organism in molecular genetics.
• Bacillus subtilis - an endospore forming Gram-positive bacterium
• Caulobacter crescentus - a bacterium that divides into two distinct cells used to study cellular differentiation.
• Mycoplasma genitalium - a minimal organism
• Vibrio fischeri - quorum sensing, bioluminescence and animal-bacterial symbiosis with Hawaiian Bobtail Squid
• Synechocystis, a photosynthetic cyanobacteria widely used in photosynthesis research.
• Pseudomonas fluorescens, a soil bacterium that readily diversifies into different strains in the lab.

Eukaryotes

Eukaryotes include:

Protists

• Protists:

• Chlamydomonas reinhardtii - a unicellular green alga used to study photosynthesis, flagella and motility, regulation of metabolism, cell-cell recognition and adhesion, response to nutrient deprivation and many other topics. Chlamydomonas reinhardtii has a well-studied genetics, with many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes.^[5] Sequencing of the Chlamydomonas reinhardtii genome was reported in October 2007.^[6] A Chlamydomonas genetic stock center exists at Duke University, and an international Chlamydomonas research interest group meets on a regular basis to discuss research results. Chlamydomonas is easy to grow on an inexpensive defined medium.
• Dictyostelium discoideum is used in molecular biology and genetics (its genome has been sequenced), and is studied as an example of cell communication, differentiation, and programmed cell death.
• Tetrahymena thermophila - a free living freshwater ciliate protozoan.
• Emiliania huxleyi - a unicellular marine coccolithophore alga, extensively studied as a model phytoplankton species.

Fungi

• Fungi:

Budding yeast tomography

• Aspergillus nidulans, mold subject of genetics studies
• Coprinus cinereus, mushroom (genetic studies of mushroom development, genetic studies of meiosis) ^[7]
• Neurospora crassa - orange bread mold (genetic studies of meiosis, metabolic regulation, and circadian rhythm)^[8]
• Ashbya gossypii, cotton pathogen, subject of genetics studies (polarity, cell cycle)
• Saccharomyces cerevisiae, baker's yeast or budding yeast (used in brewing and baking)
• Schizosaccharomyces pombe, fission yeast, (cell cycle, cell polarity, RNAi, centromere structure and function, transcription)
• Ustilago maydis, dimorphic yeast and plant pathogen of maize (dimorphism, plant pathogen, transcription)

Plants

Arabidopsis thaliana

• Plants:

• Arabidopsis thaliana, currently the most popular model plant. This herbaceous dicot is a crucifer, a member of the mustard family. Its small stature and short generation time facilitates genetic studies,^[9] and many phenotypic and biochemical mutants have been mapped.^[9] Arabidopsis was the first plant to have its genome sequenced.^[9] Its genome sequence, along with a wide range of information concerning Arabidopsis, is maintained by the TAIR database.^[9]
  (Plant physiology, Developmental biology, Molecular genetics, Population genetics, Cytology, Molecular biology)
• Selaginella moellendorffii is a remnant of an ancient lineage of vascular plants and key to understanding the evolution of land plants. It has a small genome size (~110Mb) and its sequence will be released by the Joint Genome Institute in early 2008. (Evolutionary biology, Molecular biology)
• Brachypodium distachyon is an emerging experimental model grass that has many attributes that make it an excellent model for temperate cereals. (Agronomy, Molecular biology, Genetics)
• Lotus japonicus a model legume used to study the symbiosis responsible for nitrogen fixation. (Agronomy, Molecular biology)
  

  

  Lemna gibba
• Lemna gibba is a rapidly-growing aquatic monocot, one of the smallest flowering plants. Lemna growth assays are used to evaluate the toxicity of chemicals to plants in ecotoxicology. Because it can be grown in pure culture, microbial action can be excluded. Lemna is being used as a recombinant expression system for economical production of complex biopharmaceuticals. It is also used in education to demonstrate population growth curves.

Zea mays

• Maize (Zea mays L.) is a cereal grain. It is a diploid monocot with 10 large chromosome pairs, easily studied with the microscope. Its genetic features, including many known and mapped phenotypic mutants and a large number of progeny per cross (typically 100-200) facilitated the discovery of transposons ("jumping genes"). Many DNA markers have been mapped and the genome is being sequenced. (Genetics, Molecular biology, Agronomy)
• Medicago truncatula is a model legume, closely related to the common alfalfa. Its rather small genome is currently being sequenced. It is used to study the symbiosis responsible for nitrogen fixation. (Agronomy, Molecular biology)
• Mimulus is a model organism used in evolutionary and functional genomes studies. This specie pertain to Scrophulariaceae family, with ca. 120 species. Several genetic resources has been designed for the study of this genera, some are free access (http://www.mimulusevolution.org)
• Tobacco BY-2 cells is suspension cell line from tobacco (Nicotiana tabaccum). Useful for general plant physiology studies on cell level. Genome of this particular cultivar will be not sequenced (at least in near future), but sequencing of its wild species Nicotiana tabaccum is presently in progress. (Cytology, Plant physiology, Biotechnology)
• Rice (Oryza sativa) is used as a model for cereal biology. It has one of the smallest genomes of any cereal species, and sequencing of its genome is finished. (Agronomy, Molecular biology)

Physcomitrella patens

• Physcomitrella patens is a moss increasingly used for studies on development and molecular evolution of plants.^[10] It is so far the only non-vascular plant (and so the only "primitive" plant) with its genome completely sequenced.^[10] (Plant physiology, Evolutionary biology, Molecular genetics, Molecular biology)
• Populus is a genus used as a model in forest genetics and woody plant studies. It has a small genome size, grows very rapidly, and is easily transformed. The genome sequence of Poplar (Populus trichocarpa) sequence is publicly available.
• See also Chlamydomonas reinhardtii, above under Protists.

Animals

Invertebrates

Caenorhabditis elegans

• Arbacia punctulata, the purple-spined sea urchin, classical subject of embryological studies
• Aplysia, a sea slug, whose ink release response serves as a model in neurobiology and whose growth cones serve as a model of cytoskeletal rearrangements.
• Caenorhabditis elegans, a nematode, usually called C. elegans^[11] - an excellent model for understanding the genetic control of development and physiology. C. elegans was the first multicellular organism whose genome was completely sequenced
• Ciona intestinalis, a sea squirt
• Drosophila, usually the species Drosophila melanogaster - a kind of fruit fly, famous as the subject of genetics experiments by Thomas Hunt Morgan and others. Easily raised in lab, rapid generations, mutations easily induced, many observable mutations. Recently, Drosophila has been used for neuropharmacological research^[12]. (Molecular genetics, Population genetics, Developmental biology).
• Euprymna scolopes, the Hawaiian bobtail squid, model for animal-bacterial symbiosis, bioluminescent vibrios
• Hydra (genus), a Cnidarian, is the model organism to understand the processes of regeneration and morphogenesis, as well as the evolution of bilaterian body plans
• Loligo pealei, a squid, subject of studies of nerve function because of its giant axon (nearly 1 mm diameter, roughly a thousand times larger than typical mammalian axons)
• Oikopleura dioica^[13], an appendicularia, a free-swimming tunicate (or urochordate))
• Pristionchus pacificus, a roundworm used in evolutionary developmental biology in comparative analyses with C. elegans
• Stomatogastric ganglion of various arthropod species; a model for motor pattern generation seen in all repetitive motions
• Strongylocentrotus purpuratus, the purple sea urchin, widely used in developmental biology
• Symsagittifera roscoffensis, a flatworm, subject of studies of bilaterian body plan development
• Tribolium castaneum, the flour beetle - a small, easily kept darkling beetle used especially in behavioural ecology experiments

Vertebrates

Laboratory mice

• Cavia porcellus, the guinea pig, used by Robert Koch and other early bacteriologists as a host for bacterial infections, hence a byword for "laboratory animal" even though less commonly used today
• Chicken (Gallus gallus domesticus) - used for developmental studies, as it is an amniote and excellent for micromanipulation (e.g. tissue grafting) and over-expression of gene products
• Cat (Felis cattus) - used in neurophysiological research
• Dog (Canis lupus familiaris) - an important respiratory and cardiovascular model, also contributed to the discovery of classical conditioning.
• Hamster - first used to study kala-azar (leishmaniasis)
• Mouse (Mus musculus) - the classic model vertebrate. Many inbred strains exist, as well as lines selected for particular traits, often of medical interest, e.g. body size, obesity, muscularity. (Quantitative genetics, Molecular evolution, Genomics)
• Homo sapiens (humans) - used in various clinical studies
• Lamprey - spinal cord research
• Oryzias latipes, Medaka (the Japanese ricefish) is an important model in developmental biology, and has the advantage of being much sturdier than the traditional Zebrafish
• Rat (Rattus norvegicus) - particularly useful as a toxicology model; also particularly useful as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse. (Molecular evolution, Genomics)
• Rhesus macaque - used for studies on infectious disease and cognition
• Sigmodon hispidus - Cotton rat formerly used in polio research
• Taeniopygia guttata or zebra finch - used in the study of the song system of songbirds and the study of non-mammalian auditory systems
• Takifugu rubripes, a pufferfish - has a small genome with little junk DNA
• Xenopus laevis, the African clawed frog - used in developmental biology because of its large embryos and high tolerance for physical and pharmacological manipulation
• Zebrafish (Danio rerio), a freshwater fish, has a nearly transparent body during early development, which provides unique visual access to the animal's internal anatomy. Zebrafish are used to study development, toxicology and toxicopathology,^[14] specific gene function and roles of signaling pathways.

Model organisms used for specific research objectives

Sexual selection and sexual conflict

• Callosobruchus maculatus, the bruchid beetle
• Chorthippus parallelus, the meadow grasshopper
• Coelopidae - seaweed flies
• Diopsidae - stalk-eyed flies
• Drosophila spp. - fruit flies
• Gryllus bimaculatus, the field cricket
• Scathophaga stercoraria, the yellow dung fly

Hybrid zones

• Bombina bombina and variegata
• Podisma spp. in the Alps
• Caledia captiva (Orthoptera) in eastern Australia

Ecological genomics

• Daphnia pulex, an environmental indicator model organism

Table of model genetic organisms

This table indicates the status of the genome sequencing project for each organism as well as whether the organism exhibits homologous recombination and the state of knowledge of the organism's biochemical pathways.

See also

• Animal model
• Ensembl genome database of model organisms
• History of model organisms
• Animals in space
• Animal testing
• Animal testing on invertebrates
• Animal testing on rodents
• Mouse models of colorectal and intestinal cancer
• Generic Model Organism Database
• History of animal testing
• RefSeq - the Reference Sequence database
• Genome project

References

1. ^ Fields S, Johnston M (Mar 2005). "Cell biology. Whither model organism research?". Science 307 (5717): 1885–6. doi:10.1126/science.1108872. PMID 15790833. http://www.sciencemag.org/cgi/content/summary/307/5717/1885. 
2. ^ Fox, Michael Allen (1986). The Case for Animal Experimention: An Evolutionary and Ethical Perspective. Berkeley and Los Angeles, California: University of California Press. ISBN 0-520-05501-2. 
3. ^ What are model organisms?
4. ^ NIH model organisms
5. ^ Chlamydomonas reinhardtii resources at the Joint Genome Institute
6. ^ Chlamydomonas genome sequenced published in Science, October 12, 2007
7. ^ Kües U (June 2000). "Life history and developmental processes in the basidiomycete Coprinus cinereus". Microbiol. Mol. Biol. Rev. 64 (2): 316–53. PMID 10839819. PMC 98996. http://mmbr.asm.org/cgi/pmidlookup?view=long&pmid=10839819. 
8. ^ Davis, Rowland H. (2000). Neurospora: contributions of a model organism. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-512236-4. 
9. ^ ^{a b c d} About Arabidopsis on The Arabidopsis Information Resource page (TAIR)
10. ^ ^{a b} Rensing SA, Lang D, Zimmer AD, et al. (Jan 2008). "The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants". Science 319 (5859): 64–9. doi:10.1126/science.1150646. PMID 18079367. http://www.sciencemag.org/cgi/content/abstract/319/5859/64. 
11. ^ Riddle, Donald L. (1997) (Full text). C. elegans II. Plainview, N.Y: Cold Spring Harbor Laboratory Press. ISBN 0-87969-532-3. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=ce2.TOC. 
12. ^ Manev H, Dimitrijevic N, Dzitoyeva S. (2003). "Techniques: fruit flies as models for neuropharmacological research.". Trends Pharmacol Sci. 24 (1): 41–3. doi:10.1016/S0165-6147(02)00004-4. http://linkinghub.elsevier.com/retrieve/pii/S0165614702000044. 
13. ^ The Appendicularia Facility at the Sars International Centre for Marine Molecular Biology
14. ^ Spitsbergen JM, Kent ML (2003). "The state of the art of the zebrafish model for toxicology and toxicologic pathology research—advantages and current limitations". Toxicol Pathol 31 (Suppl): 62–87. doi:10.1080/01926230390174959. PMID 12597434. PMC 1909756. http://tpx.sagepub.com/cgi/pmidlookup?view=long&pmid=12597434. 

External links

• Wellcome Trust description of model organisms
• WWW Virtual Library guide to several model organism resource lists
• The Generic Model Organism Database project
• The Model Organism Database ftp site and info
• The US National Institutes of Health page
• Model organisms in developmental biology
• Ludwig-Maximillians-Universität Department Biologie II
• Zebrafish GenomeWiki Community Annotation Project mainteined by the Institute of Genomics and Integrative Biology
• Workhorse Zoo by Adam Zaretsky

• Mandoli DF, Olmstead R (2000): The importance of emerging model systems in plant biology. Journal of plant growth regulation 19 (3): 249-252
• Tuskan GA, Difazio S, Jansson S, et al. (Sep 2006). "The genome of black cottonwood, Populus trichocarpa (Torr. & Gray)". Science 313 (5793): 1596–604. doi:10.1126/science.1128691. PMID 16973872. 
• Sequencing Project, International Rice Genome (Aug 2005). "The map-based sequence of the rice genome". Nature 436 (7052): 793–800. doi:10.1038/nature03895. PMID 16100779. 
• FishMap: The Zebrafish Community Genomics Browser maintained at the Institute of Genomics and Integrative Biology
• EcoliWiki is the community annotation component of EcoliHub whose goal is to provide an information resource on the model organism E. coli K-12, phages, plasmids, and mobile genetic elements.