H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 12
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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. For example, the endsof chromosomes, the telomeres, are extremely dilute in mostcells. Human cells typically contain 92 telomeres (46 chromosomes 2 ends per chromosome). In contrast, some protozoa with unusual “fragmented” chromosomes containmillions of telomeres per cell.
Recent discoveries abouttelomere structure have benefited greatly from using this natural variation for experimental advantage.individual proteins, hundreds of macromolecular machines,and most of our organelles, all as a result of our shared evolutionary history. New insights into molecular cell biologyarising from genomics are leading to a fuller appreciation ofthe elegant molecular machines that arose during billions ofyears of genetic tinkering and evolutionary selection for themost efficient, precise designs. Despite all that we currentlyknow about cells, many new proteins, new macromolecularassemblies, and new activities of known ones remain to bediscovered. Once a more complete description of cells is inhand, we will be ready to fully investigate the rippling, flowing dynamics of living systems.1.5 A Genome Perspectiveon EvolutionAs humans, we probably have a biased and somewhat exaggerated view of our status in the animal kingdom.
Pride inour swollen forebrain and its associated mental capabilitiesmay blind us to the remarkably sophisticated abilities ofother species: navigation by birds, the sonar system of bats,homing by salmon, or the flight of a fly.Comprehensive studies of genes and proteins from many organisms are giving us an extraordinary documentation of thehistory of life.
We share with other eukaryotes thousands ofMetabolic Proteins, the Genetic Code,and Organelle Structures Are Nearly UniversalEven organisms that look incredibly different share many biochemical properties. For instance, the enzymes that catalyzedegradation of sugars and many other simple chemical reactions in cells have similar structures and mechanisms in mostliving things. The genetic code whereby the nucleotide sequences of mRNA specifies the amino acid sequences of proteins can be read equally well by a bacterial cell and a humancell. Because of the universal nature of the genetic code, bacterial “factories” can be designed to manufacture growth factors, insulin, clotting factors, and other human proteins withtherapeutic uses.
The biochemical similarities among organisms also extend to the organelles found in eukaryotic cells.The basic structures and functions of these subcellular components are largely conserved in all eukaryotes.Computer analysis of DNA sequence data, now availablefor numerous bacterial species and several eukaryotes, canlocate protein-coding genes within genomes. With the aid ofthe genetic code, the amino acid sequences of proteins can bededuced from the corresponding gene sequences. Althoughsimple conceptually, “finding” genes and deducing the aminoacid sequences of their encoded proteins is complicated inpractice because of the many noncoding regions in eukaryotic DNA (Chapter 9).
Despite the difficulties and occasionalambiguities in analyzing DNA sequences, comparisons of thegenomes from a wide range of organisms provide stunning,compelling evidence for the conservation of the molecularmechanisms that build and change organisms and for thecommon evolutionary history of all species.Many Genes Controlling DevelopmentAre Remarkably Similar in Humansand Other Animals1.5 • A Genome Perspective on Evolution(a)GenesFlyMammal(b)(c)(d)(e)27 FIGURE 1-26 Similar genes, conserved during evolution,regulate many developmental processes in diverse animals.Insects and mammals are estimated to have had a commonancestor about half a billion years ago.
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