H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 11
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Similar studies with different organisms and celltypes are revealing what is universal about the genes involvedin cell division and what is specific to particular organisms.The entire complement of proteins in a cell, its proteome,is controlled in part by changes in gene transcription. Theregulated synthesis, processing, localization, and degradationof specific proteins also play roles in determining the proteome of a particular cell, and the association of certain proteins with one another is critical to the functional abilities1.4 • Investigating Cells and Their Parts▲ FIGURE 1-23 DNA microarray analysis gives a globalview of changes in transcription following addition of serumto cultured human cells.
Serum contains growth factors thatstimulate nondividing cells to begin growing and dividing. DNAmicroarray analysis can detect the relative transcription of genesin two different cell populations (see Figure 9-35). The microarrayconsists of tiny spots of DNA attached to a microscope slide.Each spot contains many copies of a DNA sequence from asingle human gene. One preparation of RNA, containing all thedifferent types of RNA being made in nongrowing cells culturedwithout serum, is labeled with green fluorescent molecules.Another RNA population from growing, serum-treated, cells islabeled with red.
The two are mixed and hybridized to the slide,where they "zipper up" with their corresponding genes. Greenspots (e.g., spot 3) therefore indicate genes that are transcribedin nondividing (serum-deprived) cells; red spots (e.g., spot 4)indicate genes that are transcribed in dividing cells, and yellowspots (e.g., spots 1 and 2) indicate genes that are transcribedequally in dividing and nondividing cells.
[From V. R. Iyer et al., 1999,23bodies require an enormous amount of communication anddivision of labor. During the development of multicellular organisms, differentiation processes form hundreds of celltypes, each specialized for a particular task: transmission ofelectrical signals by neurons, transport of oxygen by redblood cells, destruction of infecting bacteria by macrophages, contraction by muscle cells, chemical processing byliver cells.Many of the differences among differentiated cells aredue to production of specific sets of proteins needed to carryout the unique functions of each cell type. That is, only asubset of an organism’s genes is transcribed at any given timeor in any given cell. Such differential gene expression at different times or in different cell types occurs in bacteria, fungi,plants, animals, and even viruses.
Differential gene expression is readily apparent in an early fly embryo in which allthe cells look alike until they are stained to detect the proteins encoded by particular genes (Figure 1-24). Transcription can change within one cell type in response to anexternal signal or in accordance with a biological clock;some genes, for instance, undergo a daily cycle between lowand high transcription rates.Science 283:83.]of cells. New techniques for monitoring the presence and interactions of numerous proteins simultaneously, called proteomics, are one way of assembling a comprehensive viewof the proteins and molecular machines important for cellfunctioning. The field of proteomics will advance dramatically once high-throughput x-ray crystallography, currentlyunder development, permits researchers to rapidly determinethe structures of hundreds or thousands of proteins.Developmental Biology Reveals Changes inthe Properties of Cells as They SpecializeAnother approach to viewing cells comes from studying howthey change during development of a complex organism.Bacteria, algae, and unicellular eukaryotes (protozoans,yeasts) often, but by no means always, can work solo.
Theconcerted actions of the trillions of cells that compose our▲ FIGURE 1-24 Differential gene expression can bedetected in early fly embryos before cells aremorphologically different. An early Drosophila embryo hasabout 6000 cells covering its surface, most of which areindistinguishable by simple light microscopy. If the embryo ismade permeable to antibodies with a detergent that partiallydissolves membranes, the antibodies can find and bind to theproteins they recognize. In this embryo we see antibodiestagged with a fluorescent label bound to proteins that are in thenuclei; each small sphere corresponds to one nucleus. Threedifferent antibodies were used, each specific for a differentprotein and each giving a distinct color (yellow, green, or blue) ina fluorescence microscope.
The red color is added to highlightoverlaps between the yellow and blue stains. The locations of thedifferent proteins show that the cells are in fact different at thisearly stage, with particular genes turned on in specific stripes ofcells. These genes control the subdivision of the body intorepeating segments, like the black and yellow stripes of a hornet.[Courtesy of Sean Carroll, University of Wisconsin.]24CHAPTER 1 • Life Begins with CellsProducing different kinds of cells is not enough to make anorganism, any more than collecting all the parts of a truck inone pile gives you a truck. The various cell types must be organized and assembled into all the tissues and organs. Evenmore remarkable, these body parts must work almost immediately after their formation and continue working during thegrowth process. For instance, the human heart begins to beatwhen it is less than 3 mm long, when we are mere 23-day-oldembryos, and continues beating as it grows into a fist-sizemuscle.
From a few hundred cells to billions, and still ticking.In the developing organism, cells grow and divide atsome times and not others, they assemble and communicate,they prevent or repair errors in the developmental process,and they coordinate each tissue with others. In the adult organism, cell division largely stops in most organs. If part ofan organ such as the liver is damaged or removed, cell division resumes until the organ is regenerated. The legend goesthat Zeus punished Prometheus for giving humans fire bychaining him to a rock and having an eagle eat his liver.
Thepunishment was eternal because, as the Greeks evidentlyknew, the liver regenerates.Developmental studies involve watching where, when,and how different kinds of cells form, discovering which signals trigger and coordinate developmental events, and understanding the differential gene action that underliesdifferentiation (Chapters 15 and 22). During developmentwe can see cells change in their normal context of other cells.Cell biology, biochemistry, cell biology, genetics, and genomics approaches are all employed in studying cells duringdevelopment. FIGURE 1-25 Each experimental organism used in cellbiology has advantages for certain types of studies.
Virusesand bacteria have small genomes amenable to geneticdissection. Many insights into gene control initially came fromstudies with these organisms. The yeast Saccharomycescerevisiae has the cellular organization of a eukaryote but is arelatively simple single-celled organism that is easy to grow andto manipulate genetically. In the nematode worm Caenorhabditiselegans, which has a small number of cells arranged in a nearlyidentical way in every worm, the formation of each individual cellcan be traced.
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.
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