is one of the most intensively studied eukarvotic model organisms in molecular and cell biology.much like Escherichia coli as the model prokaryote.It is the microorganism behind the most cerevisiae cells are round to ovoid,5-10 micrometres in diameter.It reproduces by a division process known as budding. It is useful in studying the cell cycle because it is easy to culture,but,as a eukaryote,it shares the complex internal cell structure of plants and animals.S. cerevisiae was the first eukaryotic genome that was completely sequenced.The yeas genome database is highly annotated and remains a very important tool for developing basic knowledge about the function and organization of eukaryotic cell genetics and physiology.The genome is composed of about 13,000,000 base pairs and 6 275 genes compactly organised on 16 chromosomes only about 5 800 of se are believed to true func ional genes.It is estimated that yeast shares abou There are two forms in which yeast cells can survive and grow.haploid and diploid.The haploid cells undergo a simple lifecycle of mitosis and growth,and under conditions of high stress will generally simply die.The diploid cells(the Prefere ntial 'form'of imilarly underg imple lif of mitosis and producing a variety of haploid spores.which can go on to mate(conjugate). reforming the diploid. Saccharomces cerevisiae is a widely used model organism in science.and therefore also evisige has obtained positio of it industry (e.g.beer,bread and wine fermentation,ethanol production).Additionally,yeasts are comparatively similar in structure to human cells.both being eukaryotic,in contrast to the prokaryotes (bacteria and archaea).Many proteins important in human biology were first discovered by studying their homologs in yeast,these proteins include cell cycle and protein-processing enzymes.The petiter mutation in of particular interest All these features make this yeast an extremely convenient organism for genetic studies,as does one further property:its genome,by eucaryotic standards,is exceptionally small.Nevertheless.it suffices for all the basic tasks that every eucaryotic cell must perform.As we shall know,studies on yeasts(using bothS. cerevisiae and othe r species ) ave provided a key to the understanding of many crucial processes.These include the eucaryotic cell-division cycle -the critical chair of events by which the nucleus and all the other components of a cell are duplicated and parceled out to create two daughter cells from one.The control system that governs this process has been so well conserved over the course of evolution that many of its nents can func ion inte eably in yeast and ht mutant yeast lacking an essential yeast cell-division-cycle gene is supplied copy of the homologous cell-division-cycle gene from a human,the yeast is cured of its defect and becomes able to divide normally
31 is one of the most intensively studied eukaryotic model organisms in molecular and cell biology, much like Escherichia coli as the model prokaryote. It is the microorganism behind the most common type of fermentation. Saccharomyces cerevisiae cells are round to ovoid, 5–10 micrometres in diameter. It reproduces by a division process known as budding. It is useful in studying the cell cycle because it is easy to culture, but, as a eukaryote, it shares the complex internal cell structure of plants and animals. S. cerevisiae was the first eukaryotic genome that was completely sequenced. The yeast genome database is highly annotated and remains a very important tool for developing basic knowledge about the function and organization of eukaryotic cell genetics and physiology. The genome is composed of about 13,000,000 base pairs and 6,275 genes, compactly organised on 16 chromosomes. Only about 5,800 of these are believed to be true functional genes. It is estimated that yeast shares about 23% of its genome with that of humans. There are two forms in which yeast cells can survive and grow, haploid and diploid. The haploid cells undergo a simple lifecycle of mitosis and growth, and under conditions of high stress will generally simply die. The diploid cells (the preferential 'form' of yeast) similarly undergo a simple lifecycle of mitosis and growth, but under conditions of stress can undergo sporulation, entering meiosis and producing a variety of haploid spores, which can go on to mate (conjugate), reforming the diploid. Saccharomyces cerevisiae is a widely used model organism in science, and therefore also one of the most studied (along with E. coli). S. cerevisiae has obtained this important position because of its established use in industry (e.g. beer, bread and wine fermentation, ethanol production). Additionally, yeasts are comparatively similar in structure to human cells, both being eukaryotic, in contrast to the prokaryotes (bacteria and archaea). Many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. The petite mutation in S. cerevisiae is of particular interest. All these features make this yeast an extremely convenient organism for genetic studies, as does one further property: its genome, by eucaryotic standards, is exceptionally small. Nevertheless, it suffices for all the basic tasks that every eucaryotic cell must perform. As we shall know, studies on yeasts (using both S. cerevisiae and other species) have provided a key to the understanding of many crucial processes. These include the eucaryotic cell-division cycle—the critical chain of events by which the nucleus and all the other components of a cell are duplicated and parceled out to create two daughter cells from one. The control system that governs this process has been so well conserved over the course of evolution that many of its components can function interchangeably in yeast and human cells: if a mutant yeast lacking an essential yeast cell-division-cycle gene is supplied with a copy of the homologous cell-division-cycle gene from a human, the yeast is cured of its defect and becomes able to divide normally
2 5 3 4 Caenorhaditiselegans caenorhabditis elegans is a small harmless relative of the eelworm that attacks crops.With a life cycle of only a few days,an ability to survive in a free erindefinitely in state uspended an a simple body pan that is el suted for ideal model organism.C.elegans develops with clockwork precision from a fertilized egg cell into an adult worm with exactly 959 body cells(plus a variable number of egg and sperm cells)-an unusual degree of regularity for an animal.We now have a ion of the of events by which this occurs,as the cells divide,move,and change their characters acc ling to stric ct and predictable rules.The genome of 97 million nucleotide pairs code for about 19,000 proteins and a wealth of mutants are available for the testing of gene functions Although the worm has a body plan very different from our own.the conservation of biological mechanisms has be sufficient for the wo rm to provide a valuable model for many of the processes that occur in the humar ody.Studies of th worm help us to understand,for example,the programs of cell division and cell death that determine the numbers of cells in the body-a topic of great importance in developmental biology and cancer research. C.elegans is studied as a model organism for a variety of reasons.Strains are zen.Wher thawed th remai le allowing long-term storage.Because the complete cell lineage of the species ha been determined,C.elegans has proven especially useful for studying cellular differentiation. From a research perspective,C.elegans has the advantage of being a eukar tic ism that is simplee ough to b estudied ingreat detail. The deve pmental fate ofevery single somatic cell(959 in the adult hermaphrodite 1031 in the adult male)has been mapped out.These patterns of cell lineage are largely invariant between individuals.in contrast to mammals where cell development from the embryo is more largely dependent on cellular cues.In both sexes,a large number of additional cells(131 in the hermaphrodite,most of which would ot erwise become neurons),are eliminat ed by programmed cell death (apoptosis) In addition.C.elegans is one of the simplest organisms with a nervous system. In the hermaphrodite,this comprises 302 neurons whose pattern of connectivity has been completely mapped out,and shown to be a small-world network.Research has chanis nsible for several of the m interesting behaviors shown byC.el,incudnhe xis,thermotaxis mechanotransduction.and male mating behavior.Unusually.the neurons fire no action potentals. a useful feature of c.elegans is that it is relatively straightforward to disrupt the function of specific genes by RNA interference(RNAi).Sile ncing the function of a gene in this way n ow a researcher to infer wha t the unction of that gene may be.The nematode can either be soaked in(or injected with)a solution of double stranded RNA,the sequence of which is complementary to the sequence of
32 2.5.3.4 Caenorhaditiselegans. Caenorhabditis elegans is a small, harmless relative of the eelworm that attacks crops. With a life cycle of only a few days, an ability to survive in a freezer indefinitely in a state of suspended animation, a simple body plan, and an unusual life cycle that is well suited for genetic studies, it is an ideal model organism. C. elegans develops with clockwork precision from a fertilized egg cell into an adult worm with exactly 959 body cells (plus a variable number of egg and sperm cells)—an unusual degree of regularity for an animal. We now have a minutely detailed description of the sequence of events by which this occurs, as the cells divide, move, and change their characters according to strict and predictable rules. The genome of 97 million nucleotide pairs code for about 19,000 proteins and a wealth of mutants are available for the testing of gene functions. Although the worm has a body plan very different from our own, the conservation of biological mechanisms has been sufficient for the worm to provide a valuable model for many of the processes that occur in the human body. Studies of the worm help us to understand, for example, the programs of cell division and cell death that determine the numbers of cells in the body—a topic of great importance in developmental biology and cancer research. C. elegans is studied as a model organism for a variety of reasons. Strains are cheap to breed and can be frozen. When subsequently thawed they remain viable, allowing long-term storage. Because the complete cell lineage of the species has been determined, C. elegans has proven especially useful for studying cellular differentiation. From a research perspective, C. elegans has the advantage of being a multicellular eukaryotic organism that is simple enough to be studied in great detail. The developmental fate of every single somatic cell (959 in the adult hermaphrodite; 1031 in the adult male) has been mapped out. These patterns of cell lineage are largely invariant between individuals, in contrast to mammals where cell development from the embryo is more largely dependent on cellular cues. In both sexes, a large number of additional cells (131 in the hermaphrodite, most of which would otherwise become neurons), are eliminated by programmed cell death (apoptosis). In addition, C. elegans is one of the simplest organisms with a nervous system. In the hermaphrodite, this comprises 302 neurons whose pattern of connectivity has been completely mapped out, and shown to be a small-world network. Research has explored the neural mechanisms responsible for several of the more interesting behaviors shown by C. elegans, including chemotaxis, thermotaxis, mechanotransduction, and male mating behavior. Unusually, the neurons fire no action potentials. A useful feature of C. elegans is that it is relatively straightforward to disrupt the function of specific genes by RNA interference (RNAi). Silencing the function of a gene in this way can sometimes allow a researcher to infer what the function of that gene may be. The nematode can either be soaked in (or injected with) a solution of double stranded RNA, the sequence of which is complementary to the sequence of
the gene that the researcher wishes to disable.alternatively.worms can be fed on transformed bacteria hich exp ress the double stranded RNA of interest elegan has als so been useful in the study of meiosis.As sperm and egg nucle move down the length of the gonad,they undergo a temporal progression through meiotic events.This progression means that every nucleus at a given position in the gonad will be at roughly the same step in meiosis.eliminating the difficulties of heterogeneous populations of cells. The organism been identified asa mode for nicotine dependenceas i has been found to experience the same symptoms humans experience when they quit smoking. As for most model organisms.there is a dedicated online database for the species that is actively curated by scientists working in this field.The WormBase database ollate all published information on C.eleg s and other related nematodes.A rew ard has been advertised on their websit .for the finder of a new species of closely related nematode.Such a discovery would broaden research opportunities with the worm. 2.5.3.5 Drosophila melanogaster.The fruit fly,Drosophila melanogaster,has been the most pop oular eukaryo used in cla oms.It has bee en used in heredity and biom edical research where the aims are to understand h man genetics and developmental processes.It is also a popular model for teaching Mendelian genetics.Drosophila is very popular and successful as a model organism,particularly in genetics and developmental biology.There are several reasons:it is small and ratory.It has ashort g ration time (about two weeks)and dity(females can lay 800 eggs in lif one egg pe 30m ith ough food).The mature larvae show giant chromosomes in the salivary gland called polytene chromosomes-"puffs"indicate regions of transcription and hence gene activity.It has only four pairs of chromosomes:three autosomes,and one sex chromosome.Males do not show meiotic recombination.facilitating genetic studies Genetic transformation technic ques have been available since 1987.Its mpact genome was sequenced and first published in 2.5.3.6 The mouse.The mouse is the model organism most closely related to humans.The mouse and human genomes are approximately the same size,contain the same number of genes and show extensive synteny (conserved gene order).Most human genes have mouse counterparts and the functions of these g nes are closely related.Mutations tha at cause dis es in humans oft ten cause similar dise ases mice Importantly,mice have genes that are not represented in other animal models(the fruit fly and nematode worm )including the genes of the immune system The similarities discussed above probably apply to most mammals,but the mouse has further properties that make it an ideal model organism.Mice are small, easy to main and (compare ed to m mals)hav a short breeding cycle(about 2 months).They can produce 10-15 offspring per litter and approximately one litter every month.This makes them suitable for genetic analysis Many mutants are available and new mutations can be introduced easily by
33 the gene that the researcher wishes to disable. Alternatively, worms can be fed on genetically transformed bacteria which express the double stranded RNA of interest. C. elegans has also been useful in the study of meiosis. As sperm and egg nuclei move down the length of the gonad, they undergo a temporal progression through meiotic events. This progression means that every nucleus at a given position in the gonad will be at roughly the same step in meiosis, eliminating the difficulties of heterogeneous populations of cells. The organism has also been identified as a model for nicotine dependence as it has been found to experience the same symptoms humans experience when they quit smoking. As for most model organisms, there is a dedicated online database for the species that is actively curated by scientists working in this field. The WormBase database attempts to collate all published information on C. elegans and other related nematodes. A reward of $5000 has been advertised on their website, for the finder of a new species of closely related nematode. Such a discovery would broaden research opportunities with the worm. 2.5.3.5 Drosophila melanogaster. The fruit fly, Drosophila melanogaster, has been the most popular eukaryotic organism used in classrooms. It has been used in heredity and biomedical research where the aims are to understand human genetics and developmental processes. It is also a popular model for teaching Mendelian genetics. Drosophila is very popular and successful as a model organism,particularly in genetics and developmental biology. There are several reasons: it is small and easy to grow in the laboratory. It has a short generation time (about two weeks) and high fecundity (females can lay >800 eggs in life time i.e. one egg per 30 min with enough food). The mature larvae show giant chromosomes in the salivary glands called polytene chromosomes—"puffs" indicate regions of transcription and hence gene activity. It has only four pairs of chromosomes: three autosomes, and one sex chromosome. Males do not show meiotic recombination, facilitating genetic studies. Genetic transformation techniques have been available since 1987. Its compact genome was sequenced and first published in 2000. 2.5.3.6 The mouse. The mouse is the model organism most closely related to humans. The mouse and human genomes are approximately the same size, contain the same number of genes and show extensive synteny (conserved gene order). Most human genes have mouse counterparts and the functions of these genes are closely related. Mutations that cause diseases in humans often cause similar diseases in mice. Importantly, mice have genes that are not represented in other animal models (the fruit fly and nematode worm ), including the genes of the immune system. The similarities discussed above probably apply to most mammals, but the mouse has further properties that make it an ideal model organism. Mice are small, easy to maintain in the laboratory and (compared to most mammals) have a short breeding cycle (about 2 months). They can produce 10-15 offspring per litter and approximately one litter every month. This makes them suitable for genetic analysis. Many mutants are available and new mutations can be introduced easily by
irradiation,feeding with chemical mutagens or inserting DNA fragments into the genome to interrupt genes. The mouse is the model organism most closely related to humans.The suitabilit of mice for genetic analysis is enhanced by the availability of different species,such as Mus musculis and Mus spretus,which can be used for interspecific crosses.The advantage of this approach is that the different species are likely to have different DNA sequences at most polymorphic sites in the genome.Therefore,the cific hybrids produ m such crosse re extensively hete to make finely detailed genetic maps 2 us and sses can therefore be carried out to accurately map disease genes.It is often quicker to map a mouse disease gene and use its location to find the position of the equivalent human gene than it is to map the human gene directly.Advanced breeding strategies can be used to make specialised strains s such as co ngenics,which are gen etically identical with the exception of polymorphism for one specific gene As if the above were not enough,the mouse also has a string of unique technological advantages.Gene transfer technology is highly advanced,so transgenic mice can be created carrying any foreign gene of interest.Also.the mouse is the only vertebrate species in which pre-selectedg es can be deliberately exact replicas of the genetic defects that cause diseases in humans.For some reason certain complex diseases are difficult to replicate in the mouse and in such cases the rat is often a suitable alternative. 2.5.3.7 Arabidopsis thaliana.Arabidopsis is widely used as one of the model rgan sms for tudy plant scien including gene ics and plant develor ent It sciences tha mice and fruit flies(Dro ophila)play in animal biology.Although Arabidopsis thaliana has little direct significance for agriculture.it has several traits that make it a useful model for understanding the genetic,cellular,and molecular biology of flowering plants. The small size of its genome make Arabidopsis thaliana useful for genetic mapping and sequencing with about 157million base pai e chromosomes Arabidopsis has one of the smallest genomes among plants.It was the first plant genome to be sequenced,completed in 2000 by the Arabidopsis Genome Initiative Much work has been done to assign functions to its 27,000 genes and the 35,000 proteins they encode. The plant's small size and rapid life cycle are also advan ous for research Having specialized as a spring ephemeral,it has been used to found several laboratory strains that take about six weeks from germination to mature seed.The small size of the plant is convenient for cultivation in a small space and it produces many seeds.Further.the selfing nature of this plant assists genetic experiments.Also veral thousand seeds, each of the above criteria leads to rabidopsis thaliana being valued as a genetic model organis Finally,plant transformation in Arabidopsis is routine,using Agrobacterium tumefaciens to transfer DNA to the plant genome.The current protocol,termed "floral-dip",involves simply dipping a flower into a solution containing
34 irradiation, feeding with chemical mutagens or inserting DNA fragments into the genome to interrupt genes. The mouse is the model organism most closely related to humans. The suitability of mice for genetic analysis is enhanced by the availability of different species, such as Mus musculis and Mus spretus, which can be used for interspecific crosses. The advantage of this approach is that the different species are likely to have different DNA sequences at most polymorphic sites in the genome. Therefore, the interspecific hybrids produced from such crosses are extensively heterozygous and can be used to make finely detailed genetic maps. Large-scale crosses can therefore be carried out to accurately map disease genes. It is often quicker to map a mouse disease gene and use its location to find the position of the equivalent human gene than it is to map the human gene directly. Advanced breeding strategies can be used to make specialised strains such as congenics, which are genetically identical with the exception of polymorphism for one specific gene. As if the above were not enough, the mouse also has a string of unique technological advantages. Gene transfer technology is highly advanced, so transgenic mice can be created carrying any foreign gene of interest. Also, the mouse is the only vertebrate species in which pre-selected genes can be deliberately mutated in a precise manner (Knockout mice ). This means it is possible to create exact replicas of the genetic defects that cause diseases in humans. For some reason, certain complex diseases are difficult to replicate in the mouse and in such cases the rat is often a suitable alternative. 2.5.3.7 Arabidopsis thaliana. Arabidopsis is widely used as one of the model organisms for studying plant sciences, including genetics and plant development. It plays the role for agricultural sciences that mice and fruit flies (Drosophila) play in animal biology. Although Arabidopsis thaliana has little direct significance for agriculture, it has several traits that make it a useful model for understanding the genetic, cellular, and molecular biology of flowering plants. The small size of its genome make Arabidopsis thaliana useful for genetic mapping and sequencing — with about 157 million base pairsand five chromosomes, Arabidopsis has one of the smallest genomes among plants. It was the first plant genome to be sequenced, completed in 2000 by the Arabidopsis Genome Initiative. Much work has been done to assign functions to its 27,000 genes and the 35,000 proteins they encode. The plant's small size and rapid life cycle are also advantageous for research. Having specialized as a spring ephemeral, it has been used to found several laboratory strains that take about six weeks from germination to mature seed. The small size of the plant is convenient for cultivation in a small space and it produces many seeds. Further, the selfing nature of this plant assists genetic experiments. Also, as an individual plant can produce several thousand seeds, each of the above criteria leads to Arabidopsis thaliana being valued as a genetic model organism. Finally, plant transformation in Arabidopsis is routine, using Agrobacterium tumefaciens to transfer DNA to the plant genome. The current protocol, termed "floral-dip", involves simply dipping a flower into a solution containing
Agrobacterium,the DNA of interest,and a detergent.This method avoids the need The developing flower has four basic organs:sepals,petals,stamens,and carpels (which go on to form pistils).These organs are arranged in a series of whorls:four sepals on the outer whorl,followed by six petals inside this,six stamens,and a central carpel region.Homeotic mutations in Arabidopsis result in the change of one organ to anothe -in the case of the Aga nous muta tion,for example,stamens become petals and carpels are replaced with a new flower,resulting in a recursively repeated sepal-petal-petal pattern. Observations of homeotic mutations led to the formulation of the ABC model of lower development by E Coenand E Accordingto this model foral organ ide sare divided into three sses:class A genes(which affect sepals and petals).class B genes(which affect petals and stamens).and classC genes (which affect stamens and carpels).These genes code for transcription factors that combine to cause tissue specification in their respective regions during development. Although developed through study of Arabidopsis flowers,this model is generally applicable to nla 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 transfection syste )and non-specialist living requirements.Sometimes.thenm arrang ement facilitates the nism's genome fo r 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,con vation of mechan and potential ec onomic benefit.As comparative molecular bio logy has become more common,some researchers have sought model organisms from a wider assortment of lineages on the tree of life. Ouestions 1.Briefly describe the main types of iving organism recognized by biologists 2.What is meant by theC-value parad 3.How does the genetic organization of the Escherichia coli genome differ from that of a eukaryote? References 1.MA.Adams,SE.Celniker,and RA.H Drosophula melanogaster Selence 27:21852195.2000 eral.The genome sequence of 2.Brown TA.Genomes,2nd edition,New York and London:Garland Science, c2002 3.FR.Blattner,G Plunkett,and CA.Bloch,et al.The complete genome 35
35 Agrobacterium, the DNA of interest, and a detergent. This method avoids the need for tissue culture or plant regeneration Arabidopsis has been extensively studied as a model for flower development. The developing flower has four basic organs: sepals, petals, stamens, and carpels (which go on to form pistils). These organs are arranged in a series of whorls: four sepals on the outer whorl, followed by six petals inside this, six stamens, and a central carpel region. Homeotic mutations in Arabidopsis result in the change of one organ to another — in the case of the Agamous mutation, for example, stamens become petals and carpels are replaced with a new flower, resulting in a recursively repeated sepal-petal-petal pattern. Observations of homeotic mutations led to the formulation of the ABC model of flower development by E. Coen and E. Meyerowitz. According to this model floral organ identity genes are divided into three classes: class A genes (which affect sepals and petals), class B genes (which affect petals and stamens), and class C genes (which affect stamens and carpels). These genes code for transcription factors that combine to cause tissue specification in their respective regions during development. Although developed through study of Arabidopsis flowers, this model is generally applicable to other flowering plants. 2.5.4 The Characteristics of Model Organisms 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 transfection systems) 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. Questions 1. Briefly describe the main types of living organism recognized by biologists. 2. What is meant by the ‘C-value paradox'? 3. How does the genetic organization of the Escherichia coli genome differ from that of a eukaryote? References 1. MA. Adams, SE. Celniker, and RA. Holt, et al. The genome sequence of Drosophila melanogaster Science 287: 2185-2195. 2000 2. Brown TA. Genomes, 2nd edition, New York and London: Garland Science, c2002 3. FR. Blattner, G. Plunkett, and CA. Bloch, et al. The complete genome