Model Organism 3e4f50

TOP MODELS - IN BIOLOGY

RAVIKUMAR

09M51A2304

In any field of study, it is prudent to learn processes in a simple setting, understand the basis for these processes and then progress onto more complex settings to see if the same apply there as well.

WHAT IS MODEL ORGANISM? • Over the last century, research on a small number of organisms has played a pivotal role in advancing our understanding of numerous biological processes. • This is because many aspects of biology are similar in most or all organisms, but it is frequently much easier to study a particular aspect in one organism than in others. • These much-studied organisms are commonly referred to as model organisms, because each has one or more characteristics that make it suitable for laboratory study.

HOW to choose a model organism? •

It depends on what question is being asked. When studying fundamental issues of molecular biology, simpler unicellular organisms or viruses are convenient. For developmental questions, more complicated organisms should be used.

MAMMALIAN MODELS

• MOUSE • RAT • RABBIT • PIG

NON-MAMMALIAN MODELS • • • • • • • • • •

S. cerevisiae (budding yeast) S. pombe (fission yeast) Neurospora (filamentous fungus) D. discoideum (social amoeabae) C. elegans (round worm) Daphnia (water flea) D. melanogaster (fruit fly) D. rerio (zebrafish) Xenopus (frog) Gallus (chicken)

Other MODEL ORGANISMS • ARABIDOPSIS • ZEA MAYS • PISUM SATIVUM

Schizosaccharomyces pombe This image shows vegetatively growing fission yeast cells stained with DAPI to visualize the nucleus.

micromammal” “

Schizosaccharomyces pombe • Schizosaccharomyces pombe, or fission yeast, is an African brewing yeast originally isolated from millet beer. This species has a distinguished research history in studies of the cell cycle and mitosis, chromosome dynamics, and epigenetics. • With a doubling time of 2-4 hours and simple culture conditions, S. pombe is easily adapted to any molecular biology laboratory. • Investigators from non-genetic systems are frequent recruits to the fission yeast community, using S. pombe as a genetic adjunct in their laboratories, which has led to S. pombe being nicknamed the “micro-mammal”.

Neurospora crassa This image shows a rosette of maturing asci (meiotic cells) of Neurospora crassa, from Wild type x histone H1GFP. Histone H1 being a chromosomal protein, the GFP-tagged nuclei (two per spore at this stage) glow in four of the eight ascospores of each ascus; the remaining four ascospores carry the untagged nuclei from the wild-type parent.

Neurospora crassa • Neurospora crassa is a eukaryotic multicellular fungus with a sequenced 43 mb genome that contains 10,620 predicted genes – a complexity comparable to that of animal model systems such as Drosophila. Neurospora offers numerous advantages for basic research in genetics, molecular, cell, and evolutionary biology.

Neurospora crassa • Genetic analysis is readily accomplished. Haploid progeny are easily obtained as random isolates by manual isolation of ascospores or by ascospore plating. Tetrad analysis employs ordered or unordered asci to obtain the four products of individual meiotic events. • Among other pioneering contributions, Neurospora was used to demonstrate the one-gene-one-enzyme hypothesis and has provided novel examples of genetic and epigenetic gene silencing. Study of rhythmic vegetative sporulation in Neurospora has resulted in major advances toward understanding the mechanism of circadian rhythms.

Daphnia • The microcrustacean Daphnia, commonly referred to as the water flea, has been subject to intense biological investigations for over a century. • The development of genomic infrastructure coupled with a wide range of phenotypic diversity make Daphnia a versatile model system to investigate fundamental mechanisms of inheritance and development, cellular function, physiological systems, immunity response, disease, macromolecular structure/function relationships, and the genetic basis of complex phenotypic traits.

• Daphnia are an exceptional model for studying developmental and disease processes. Daphnia are transparent throughout lifeallowing for studies of tissuespecific gene expression at any life stage and direct observation of parasites and pathogens.

. Dictyostelium discoideum (Slime Mold)

Dictyostelium discoideum: Model System in Motion • The ameboid protozoan Dictyostelium discoideum is a powerful system for genetic and functional analysis of gene function. • The 34 Mb genome contains many genes that are homologous to those in higher eukaryotes and are missing in Saccharomyces cerevisiae. • The organism is uniquely suited for studing cytokinesis, cell motility, phagocytosis, chemotaxis, signal transduction, and cell differentiation during development. • Many of these processes, which play important roles in health and disease, are either absent or are less accessible in other model organisms.

• Though we may not appear to have much in common with a slime mold, scientists have discovered that many of its genes are close copies of our own. Because of its unusual properties and ability to live alone or in a group, the slime mold intrigues researchers who study cell division, movement and various aspects of organ and tissue development.

Drosophila melanogaster • In 1908, Thomas Hunt Morgan and his research associates at Columbia University placed rotting fruit on the window ledge of their laboratory. Among the menagerie of creatures that were captured, the fruit fly emerged as the animal of choice.

There is disks for appendages, eyes, antennae, the mouthparts, and genitalia. Disks are composed of fewer than 100 cells in the embryo but thousands of cells in mature larvae. The wing imaginal disk has become an important model system for the control of complex patterning processes by gradients of secreted signaling molecules.

Arabidopsis thaliana (the cress in stress) • A small flowering plant related to cabbage and mustard, Arabidopsis — the most popular model for studying plant genetics — is appealing to biologists because ithas almost all of the same genes as other flowering plants and has relatively little DNA that doesn't encode for proteins. It also grows quickly, going from seed to mature plant in only 6 weeks.

ZEAMAYS

Maize (Zea mays) • Zea mays ssp. mays is one of the world’s most important crop plants, boasting a multibillion dollar annual revenue. In addition to its agronomic importance, maize has been a keystone model organism for basic research for nearly a century. Within the cereals, which include other plant model species such as rice (Oryza sativa), sorghum (Sorghum bicolor), wheat (Triticum spp.), • Advantages large flowers and inflorescences • important crop plant

Pisum sativum

• This model was built with a rule-based computer modelling system using the information from the crystal structures of the photosynthetic reaction centres of Rhodopseudomonas viridis and Rhodobacter sphaeroides. An alignment of the primary sequences of twenty three D1, nine D2, eight bacterial L and eight bacterial M subunits predicts strong similarity between bacterial and higher plant reaction centres, especially in the transmembrane region where the cofactors responsible for electron transport are located. The ancestral relationship between the bacteria and higher plant sequences allowed both the L and M subunits to be used as structural templates as they were equally related to the higher plant polypeptides. The regions with the highest predicted structural homology were used as a framework for the construction of the structurally conserved regions.

E. COLI

E.COLI • Gram-negative rod • Facultative anaerobe • Named for Theodor Escherich • German physician (ca. 1885) • Demonstrated that particular strains were responsible for infant diarrhea and gastroenteritis • • • •

Normal flora of the mouth and intestine Protects the intestinal tract from bacterial infection Assists in digestion Produces small amounts of vitamins B12 and K

• Colonizes newborns GI tract within hours after birth • There are more than 700 different serotypes of E. coli • Distinguished by different surface proteins and polysaccharides • Escherichia coli – coli- large intestine, colon – Mammalian large intestine • Escherichia blattae – blattae. L. n. blatta cockroach – Hindgut of cockroach Blatta orientalis

Mus musculus (the mouse from your warehouse)

The predominance of the mouse model • The mouse is an excellent model for human development and disease, although, the life cycle of the mouse is slow by the standard of the nematode worm and fruit fly. • The mouse provides the link between the basic principles, discovered in simpler creatures like worms and flies, and human disease. • The chromosome complement is similar between the mouse and human (autosomomes and X,Y sex chromosomes) • Extended regions of a given mouse chromosome contain “homologous” regions of the corresponding human chromosomes. (more than 85% of the mouse genes are correspond to human genes.)

Mice are the premier model organism for human disease

Saccharomyces cerevisiae (aka, Baker's yeast)

BAKER’S YEAST Saccharomyces cerevisiae

• Features of S. cerevisiae  Have small genomes  Can be grown rapidly in the lab  Central characteristics: • they contain a discrete nucleus with multiple linear chromosomes packaged into chromatin; • their cytoplasm includes a full spectrum of intracellular organelles and cytoskeletal structures.

The Existence of Haploid and Diploid Cells Facilitate Genetic Analysis of S. cerevisiae • S. Cerevisiae can grow in either a haploid state (one copy of each chromosome) or diploid state (two copies of each chromosome). • Conversion between the two states is mediated by mating (haploid to diploid) and sporulation (diploid to haploid). •

S. Cerevisiae exist in three forms: two haploid cell types, a and а, and the diploid product of mating between these two. Figure 21-10

S. Cerevisiae Has a Small, WellCharacterized Genome • S. Cerevisiae was the first eukaryotic organism to have its genome entirely sequenced. (1996) • 1.3X106 bp, approximately 6,000 genes. • The availability of the complete genome sequence has allowed “genome-wide” approaches to studies of this organism. •

THE NEMATODE WORM, Caenorhabditis elegans • The nematode worm, C. elegans is used extensively in the fields of genetics and developmental biology. The suitability of this organism for research in these fields was first identified by Sydney Brenner and through his and other scientists’ work, the complete wiring diagram of C. elegans showing the developmental fate of each cell of the adult organism is now known. This incredible knowledge makes C. elegans a real favourite among geneticists and developmental biologists worldwide.

 Suitable characteristics: Rapid generation time Hermaphrodite reproduction producing large numbers of “selfprogeny” Sexual reproduction so that genetic stocks could be constructed A small number of transparent cells so that development could be followed directly

Figure 21-14 b The body plan of the wrom

Mutations that disrupt the formation of the vulva form a “bag of worms” (the hatched worms devour their mother The genes are components of a highly conserved receptor tyrosine kinase signaling pathway that controls cell proliferation.  and become trapped inside her skin).

• •

Mutations that inactivate this pathway eliminate vulva development. Mutations that activate this pathway cause overproliferation of the vulva precursor cells.

The cell Death Pathway Was Discovered in C. elegans Caenorhabditis elegans

Cell death is under genetic control (a mutated ced gene). Analysis of the ced mutants showed that the cell commits suicide. In males, a cell known as the linker cell is killed by its neighbor.

Zebrafish in genome research

What is zebrafish? • • • • •

Danio rerio Small freshwater fish from South Asia. 4 cm long when fully grown. Common aquarium fish. Very easy to look after.

Why use zebrafish? • Small size. • All major organs present within 5 days post fertilisation. • Short generation time (3-4 months). • Produces 300-400 eggs every 2 weeks. • Translucent embryos. • Lots of genome resources available.

The zebrafish embryo brain ear

eye

heart

swim bladder

muscle block segments ~3.5 mm

notochord

Zebrafish and human disease • Zebrafish mutants have been produced to model human diseases such as: – Alzheimer's disease – congenital heart disease – polycystic kidney disease – Duchenne muscular dystrophy – malignant melanoma – leukaemia

Chicken (Gallus gallus)

• The domesticated chicken is a modern descendant of dinosaurs. It is the premier non-mammalian model organism with a large international research community dedicated to developing and sharing information. The chicken provides a new perspective on vertebrate genome evolution. Its genome is composed of approximately one billion base pairs and approximately 20,000-23,000 genes organized in 39 chromosome pairs. Although it shares a similar number of genes, the chicken’s genome is only about a third the size of mammalian genomes. This reflects a reduction in interspersed repeat content, pseudogenes and duplications. There are hundreds of mutant chicken stocks and inbred lines available for study. Research using the chicken as a model organism has resulted in important discoveries in virology, immunology, oncology, vertebrate development, genetics and evolution.

XENOPUS

Xenopus • Model organisms are often assumed to be representative of some more inclusive taxon of which the species is a part. This assumption leads to mistaken generalizations about the evolutionary and comparative significance of the data gathered. This paper reviews comparative and evolutionary studies of Xenopus laevis and its relatives. Phylogenetic analysis of data from DNA sequences and morphology indicate that Xenopus is monophyletic and that Silurana is its sister group. The most basal lineages of Pipidae diverged prior to the breakup of Gondwana. The bizarre morphology of Xenopus is in part due to changes in the mode of metamorphosis. Speciation in Xenopus is unique among Anura in being associated with various levels of polyploidy owing to allopolyploidy.

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