B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 19
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Arabidopsis has a total genome size of approximately 220 millionnucleotide pairs, about 17 times the size of yeast’s (see Table 1–2).The World of Animal Cells Is Represented By a Worm, a Fly, aFish, a Mouse, and a HumanMulticellular animals account for the majority of all named species of livingorganisms, and for the largest part of the biological research effort. Five specieshave emerged as the foremost model organisms for molecular genetic studies. Inorder of increasing size, they are the nematode worm Caenorhabditis elegans, thefly Drosophila melanogaster, the zebrafish Danio rerio, the mouse Mus musculus,and the human, Homo sapiens. Each has had its genome sequenced.Caenorhabditis elegans (Figure 1–39) is a small, harmless relative of the eelworm that attacks crops. With a life cycle of only a few days, an ability to survive ina freezer indefinitely in a state of suspended animation, a simple body plan, andan unusual life cycle that is well suited for genetic studies (described in Chapter21), it is an ideal model organism.
C. elegans develops with clockwork precisionfrom a fertilized egg cell into an adult worm with exactly 959 body cells (plus avariable number of egg and sperm cells)—an unusual degree of regularity for ananimal. We now have a minutely detailed description of the sequence of events bywhich this occurs, as the cells divide, move, and change their character accordingto strict and predictable rules. The genome of 130 million nucleotide pairs codesfor about 21,000 proteins, and many mutants and other tools are available for thetesting of gene functions. Although the worm has a body plan very different fromour own, the conservation of biological mechanisms has been sufficient for theworm to be a model for many of the developmental and cell-biological processesthat occur in the human body. Thus, for example, studies of the worm have beencritical for helping us to understand the programs of cell division and cell deaththat determine the number of cells in the body—a topic of great importance forboth developmental biology and cancer research.Studies in Drosophila Provide a Key to Vertebrate DevelopmentThe fruit fly Drosophila melanogaster (Figure 1–40) has been used as a modelgenetic organism for longer than any other; in fact, the foundations of classicalgenetics were built to a large extent on studies of this insect.
Over 80 years ago, itprovided, for example, definitive proof that genes—the abstract units of hereditary information—are carried on chromosomes, concrete physical objects whosebehavior had been closely followed in the eukaryotic cell with the light microscope, but whose function was at first unknown. The proof depended on one ofthe many features that make Drosophila peculiarly convenient for genetics—thegiant chromosomes, with characteristic banded appearance, that are visible in0.2 mmFigure 1–39 Caenorhabditis elegans, the first multicellular organism to have itscomplete genome sequence determined. This small nematode, about 1 mm long, lives inthe soil. Most individuals are hermaphrodites, producing both eggs and sperm.
(Courtesy ofMaria Gallegos, University of Wisconsin, Madison.)1 cmFigure 1–38 Arabidopsis thaliana, theplant chosen as the primary modelfor studying plant molecular genetics.(Courtesy of Toni Hayden and the JohnInnes Foundation.)MBoC6 m1.46/1.3834Chapter 1: Cells and GenomesFigure 1–40 Drosophila melanogaster.Molecular genetic studies on this fly haveprovided the main key to understandinghow all animals develop from a fertilizedegg into an adult. (From E.B. Lewis,Science 221:cover, 1983. With permissionfrom AAAS.)1 mmsome of its cells (Figure 1–41). Specific changes in the hereditary information,manifest in families of mutant flies, were found to correlate exactly with the lossor alteration of specific giant-chromosome bands.In more recent times, Drosophila, more than any other organism, has shown ushow to trace the chain of cause and effect from the genetic instructions encodedin the chromosomal DNA to the structure of the adult multicellular body.
Drosophila mutants with body parts strangely misplaced or mispatterned providedthe key to the identification andcharacterizationMBoC6m1.48/1.40 of the genes required to makea properly structured body, with gut, limbs, eyes, and all the other parts in theircorrect places. Once these Drosophila genes were sequenced, the genomes of vertebrates could be scanned for homologs.
These were found, and their functionsin vertebrates were then tested by analyzing mice in which the genes had beenmutated. The results, as we see later in the book, reveal an astonishing degree ofsimilarity in the molecular mechanisms that govern insect and vertebrate development (discussed in Chapter 21).The majority of all named species of living organisms are insects.
Even if Drosophila had nothing in common with vertebrates, but only with insects, it wouldstill be an important model organism. But if understanding the molecular genetics of vertebrates is the goal, why not simply tackle the problem head-on? Whysidle up to it obliquely, through studies in Drosophila?Drosophila requires only 9 days to progress from a fertilized egg to an adult; itis vastly easier and cheaper to breed than any vertebrate, and its genome is muchsmaller—about 200 million nucleotide pairs, compared with 3200 million for ahuman. This genome codes for about 15,000 proteins, and mutants can now beobtained for essentially any gene.
But there is also another, deeper reason whygenetic mechanisms that are hard to discover in a vertebrate are often readily revealed in the fly. This relates, as we now explain, to the frequency of geneduplication, which is substantially greater in vertebrate genomes than in the flygenome and has probably been crucial in making vertebrates the complex andsubtle creatures that they are.The Vertebrate Genome Is a Product of Repeated DuplicationsAlmost every gene in the vertebrate genome has paralogs—other genes in thesame genome that are unmistakably related and must have arisen by gene duplication. In many cases, a whole cluster of genes is closely related to similar clusterspresent elsewhere in the genome, suggesting that genes have been duplicated inlinked groups rather than as isolated individuals.
According to one hypothesis, atan early stage in the evolution of the vertebrates, the entire genome underwentduplication twice in succession, giving rise to four copies of every gene.The precise course of vertebrate genome evolution remains uncertain, becausemany further evolutionary changes have occurred since these ancient events.20 µmFigure 1–41 Giant chromosomes fromsalivary gland cells of Drosophila.Because many rounds of DNA replicationhave occurred without an intervening celldivision, each of the chromosomes inthese unusual cells contains over 1000identical DNAMBoC6molecules,all aligned inm1.49/1.41register. This makes them easy to see inthe light microscope, where they displaya characteristic and reproducible bandingpattern.
Specific bands can be identified asthe locations of specific genes: a mutantfly with a region of the banding patternmissing shows a phenotype reflecting lossof the genes in that region. Genes that arebeing transcribed at a high rate correspondto bands with a “puffed” appearance.The bands stained dark brown in themicrograph are sites where a particularregulatory protein is bound to the DNA.(Courtesy of B. Zink and R.
Paro, fromR. Paro, Trends Genet. 6:416–421, 1990.With permission from Elsevier.)GENETIC INFORMATION IN EUKARYOTESGenes that were once identical have diverged; many of the gene copies have beenlost through disruptive mutations; some have undergone further rounds of localduplication; and the genome, in each branch of the vertebrate family tree, hassuffered repeated rearrangements, breaking up most of the original gene orderings. Comparison of the gene order in two related organisms, such as the humanand the mouse, reveals that—on the time scale of vertebrate evolution—chromosomes frequently fuse and fragment to move large blocks of DNA sequencearound.
Indeed, it is possible, as discussed in Chapter 4, that the present stateof affairs is the result of many separate duplications of fragments of the genome,rather than duplications of the genome as a whole.There is, however, no doubt that such whole-genome duplications do occurfrom time to time in evolution, for we can see recent instances in which duplicated chromosome sets are still clearly identifiable as such. The frog genus Xenopus, for example, comprises a set of closely similar species related to one anotherby repeated duplications or triplications of the whole genome.
Among these frogsare X. tropicalis, with an ordinary diploid genome; the common laboratory species X. laevis, with a duplicated genome and twice as much DNA per cell; andX. ruwenzoriensis, with a sixfold reduplication of the original genome and sixtimes as much DNA per cell (108 chromosomes, compared with 36 in X. laevis, forexample). These species are estimated to have diverged from one another withinthe past 120 million years (Figure 1–42).The Frog and the Zebrafish Provide Accessible Models forVertebrate DevelopmentFrogs have long been used to study the early steps of embryonic developmentin vertebrates, because their eggs are big, easy to manipulate, and fertilized outside of the animal, so that the subsequent development of the early embryo iseasily followed (Figure 1–43). Xenopus laevis, in particular, continues to be animportant model organism, even though it is poorly suited for genetic analysis(Movie 1.6 and see Movie 21.1).The zebrafish Danio rerio has similar advantages, but without this drawback.Its genome is compact—only half as big as that of a mouse or a human—and ithas a generation time of only about three months.
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