Lodish H. - Molecular Cell Biology (5ed, Freeman, 2003) (794361), страница 12
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The fruit fly Drosophila melanogaster, first used todiscover the properties of chromosomes, has been especiallyvaluable in identifying genes that control embryonicdevelopment. Many of these genes are evolutionarily conservedin humans. The zebrafish Danio rerio is used for rapid geneticscreens to identify genes that control development andorganogenesis. Of the experimental animal systems, mice (Musmusculus) are evolutionarily the closest to humans and haveprovided models for studying numerous human genetic andinfectious diseases. The mustard-family weed Arabidopsisthaliana, sometimes described as the Drosophila of the plantkingdom, has been used for genetic screens to identify genesinvolved in nearly every aspect of plant life. Genome sequencingis completed for many viruses and bacterial species, the yeastSaccharomyces cerevisiae, the roundworm C.
elegans, the fruitfly D. melanogaster, humans, and the plant Arabidopsis thaliana.It is mostly completed for mice and in progress for zebrafish.Other organisms, particularly frogs, sea urchins, chickens, andslime molds, continue to be immensely valuable for cell biologyresearch. Increasingly, a wide variety of other species are used,especially for studies of evolution of cells and mechanisms.
[PartChoosing the Right Experimental Organismfor the Job(a) Visuals Unlimited, Inc. Part (b) Kari Lountmaa/Science Photo Library/Photo Researchers, Inc. Part (c) Scimat/Photo Researchers, Inc. Part (d)Photo Researchers, Inc. Part (e) Darwin Dale/Photo Researchers, Inc. Part(f) Inge Spence/Visuals Unlimited, Inc. Part (g) J. M. Labat/Jancana/VisualsUnlimited, Inc. Part (h) Darwin Dale/Photo Researchers, Inc.]Our current understanding of the molecular functioning ofcells rests on studies with viruses, bacteria, yeast, protozoa,slime molds, plants, frogs, sea urchins, worms, insects, fish,chickens, mice, and humans.
For various reasons, some organisms are more appropriate than others for answering particular questions. Because of the evolutionary conservationof genes, proteins, organelles, cell types, and so forth, discoveries about biological structures and functions obtainedwith one experimental organism often apply to others. Thusresearchers generally conduct studies with the organism thatis most suitable for rapidly and completely answering thequestion being posed, knowing that the results obtained inone organism are likely to be broadly applicable. Figure 1-25summarizes the typical experimental uses of various organisms whose genomes have been sequenced completely ornearly so.
The availability of the genome sequences for theseorganisms makes them particularly useful for genetics andgenomics studies.Bacteria have several advantages as experimental organisms: They grow rapidly, possess elegant mechanisms forcontrolling gene activity, and have powerful genetics. Thislatter property relates to the small size of bacterial genomes,the ease of obtaining mutants, the availability of techniquesfor transferring genes into bacteria, an enormous wealth ofknowledge about bacterial gene control and protein functions, and the relative simplicity of mapping genes relativeto one another in the genome. Single-celled yeasts not onlyhave some of the same advantages as bacteria, but also possess the cell organization, marked by the presence of a nucleus and organelles, that is characteristic of all eukaryotes.Studies of cells in specialized tissues make use of animaland plant “models,” that is, experimental organisms with attributes typical of many others.
Nerve cells and muscle cells,for instance, traditionally were studied in mammals or increatures with especially large or accessible cells, such as thegiant neural cells of the squid and sea hare or the flight muscles of birds. More recently, muscle and nerve developmenthave been extensively studied in fruit flies (Drosophilamelanogaster), roundworms (Caenorhabditis elegans), andzebrafish in which mutants can be readily isolated. Organisms with large-celled embryos that develop outside the1.4 • Investigating Cells and Their Parts(a)25(b)VirusesBacteriaProteins involved in DNA, RNA,protein synthesisGene regulationCancer and control of cellproliferationTransport of proteins andorganelles inside cellsInfection and immunityPossible gene therapy approachesProteins involved in DNA, RNA,protein synthesis,metabolismGene regulationTargets for new antibioticsCell cycleSignaling(c)(d)Yeast (Saccharomyces cerevisiae)Roundworm (Caenorhabditiselegans)Control of cell cycle and cell divisionProtein secretion and membranebiogenesisFunction of the cytoskeletonCell differentiationAgingGene regulation and chromosomestructure(e)Development of the body planCell lineageFormation and function of thenervous systemControl of programmed cell deathCell proliferation and cancer genesAgingBehaviorGene regulation and chromosomestructure(f)Fruit fly (Drosophila melanogaster)ZebrafishDevelopment of the body planGeneration of differentiated celllineagesFormation of the nervous system,heart, and musculatureProgrammed cell deathGenetic control of behaviorCancer genes and control of cellproliferationControl of cell polarizationEffects of drugs, alcohol, pesticidesDevelopment of vertebrate bodytissuesFormation and function of brain andnervous systemBirth defectsCancer(g)(h)Mice, including cultured cellsPlant (Arabidopsis thaliana)Development of body tissuesFunction of mammalian immunesystemFormation and function of brainand nervous systemModels of cancers and otherhuman diseasesGene regulation and inheritanceInfectious diseaseDevelopment and patterning oftissuesGenetics of cell biologyAgricultural applicationsPhysiologyGene regulationImmunityInfectious diseasemother (e.g., frogs, sea urchins, fish, and chickens) are extremely useful for tracing the fates of cells as they form different tissues and for making extracts for biochemical studies.
Forinstance, a key protein in regulating mitosis was firstidentified in studies with frog and sea urchin embryosand subsequently purified from extracts (Chapter 21).26CHAPTER 1 • Life Begins with CellsUsing recombinant DNA techniques researchers canengineer specific genes to contain mutations that inactivateor increase production of their encoded proteins. Suchgenes can be introduced into the embryos of worms, flies,frogs, sea urchins, chickens, mice, a variety of plants, andother organisms, permitting the effects of activating a geneabnormally or inhibiting a normal gene function to be assessed. This approach is being used extensively to producemouse versions of human genetic diseases.
New techniquesspecifically for inactivating particular genes by injectingshort pieces of RNA are making quick tests of gene functions possible in many organisms.Mice have one enormous advantage over other experimental organisms: they are the closest to humans of any animal for which powerful genetic approaches are feasible.Engineered mouse genes carrying mutations similar to thoseassociated with a particular inherited disease in humans canbe introduced into mouse embryonic stem (ES) cells.
Thesecells can be injected into an early embryo, which is then implanted into a pseudopregnant female mouse (Chapter 9). Ifthe mice that develop from the injected ES cells exhibit diseases similar to the human disease, then the link between thedisease and mutations in a particular gene or genes is supported.
Once mouse models of a human disease are available, further studies on the molecular defects causing thedisease can be done and new treatments can be tested,thereby minimizing human exposure to untested treatments.A continuous unplanned genetic screen has been performed on human populations for millennia. Thousands ofinherited traits have been identified and, more recently,mapped to locations on the chromosomes.
Some of thesetraits are inherited propensities to get a disease; others areeye color or other minor characteristics. Genetic variations invirtually every aspect of cell biology can be found in humanpopulations, allowing studies of normal and disease statesand of variant cells in culture.Less-common experimental organisms offer possibilitiesfor exploring unique or exotic properties of cells and forstudying standard properties of cells that are exaggerated ina useful fashion in a particular animal.
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