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In many cases, a whole cluster of genes is closely related to similar clusters present elsewhere in the genome, suggesting that genes have been duplicated in linked groups rather than as isolated individuals. According to onehypothesis, at an early stage in the evolution of the vertebrates, the entiregenome underwent duplication twice in succession, giving rise to four copies ofevery gene. In some groups of vertebrates, such as fish of the salmon and carpfamilies (including the zebrafish, a popular research animal), it has been suggested that there was yet another duplication, creating an eightfold multiplicityof genes.The precise course of vertebrate genome evolution remains uncertain,because many further evolutionary changes have occurred since these ancientevents. Genes that were once identical have diverged; many of the gene copieshave been lost through disruptive mutations; some have undergone furtherrounds of local duplication; and the genome, in each branch of the vertebratefamily tree, has suffered repeated rearrangements, breaking up most of the original gene orderings.
Comparison of the gene order in two related organisms, suchas the human and the mouse, reveals that—on the time scale of vertebrate evolution—chromosomes frequently fuse and fragment to move large blocks of DNAsequence around. Indeed, it is possible, as we shall discuss in Chapter 7, that thepresent state of affairs is the result of many separate duplications of fragments ofthe genome, rather than duplications of the genome as a whole.There is, however, no doubt that such whole-genome duplications dooccur from time to time in evolution, for we can see recent instances in whichduplicated chromosome sets are still clearly identifiable as such. The frog20 mmFigure 1–49 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 DNA molecules, all aligned inregister.
This makes them easy to see inthe light microscope, where they displaya characteristic and reproducible bandingpattern. Specific bands can be identifiedas the locations of specific genes: amutant fly with a region of the bandingpattern missing shows a phenotypereflecting loss of the genes in that region.Genes that are being transcribed at ahigh rate correspond to bands with a“puffed” appearance.
The bands staineddark brown in the micrograph are siteswhere a particular regulatory protein isbound to the DNA. (Courtesy of B. Zinkand R. Paro, from R. Paro, Trends Genet.6:416–421, 1990. With permissionfrom Elsevier.)GENETIC INFORMATION IN EUCARYOTESFigure 1–50 Two species of the frog genus Xenopus. X. tropicalis, above,has an ordinary diploid genome; X. laevis, below, has twice as much DNAper cell. From the banding patterns of their chromosomes and thearrangement of genes along them, as well as from comparisons of genesequences, it is clear that the large-genome species have evolved throughduplications of the whole genome. These duplications are thought to haveoccurred in the aftermath of matings between frogs of slightly divergentXenopus species. (Courtesy of E.
Amaya, M. Offield and R. Grainger, TrendsGenet. 14:253–255, 1998. With permission from Elsevier.)genus Xenopus, for example, comprises a set of closely similar species relatedto one another by repeated duplications or triplications of the whole genome.Among these frogs are X. tropicalis, with an ordinary diploid genome; the common laboratory species X. laevis, with a duplicated genome and twice as muchDNA per cell; and X. ruwenzoriensis, with a sixfold reduplication of the originalgenome and six times as much DNA per cell (108 chromosomes, comparedwith 36 in X.
laevis, for example). These species are estimated to have divergedfrom one another within the past 120 million years (Figure 1–50).Genetic Redundancy Is a Problem for Geneticists, But It CreatesOpportunities for Evolving OrganismsWhatever the details of the evolutionary history, it is clear that most genes in thevertebrate genome exist in several versions that were once identical.
The relatedgenes often remain functionally interchangeable for many purposes. This phenomenon is called genetic redundancy. For the scientist struggling to discoverall the genes involved in some particular process, it complicates the task. If geneA is mutated and no effect is seen, it cannot be concluded that gene A is functionally irrelevant—it may simply be that this gene normally works in parallelwith its relatives, and these suffice for near-normal function even when gene Ais defective. In the less repetitive genome of Drosophila, where gene duplicationis less common, the analysis is more straightforward: single gene functions arerevealed directly by the consequences of single-gene mutations (the singleengined plane stops flying when the engine fails).Genome duplication has clearly allowed the development of more complexlife forms; it provides an organism with a cornucopia of spare gene copies,which are free to mutate to serve divergent purposes.
While one copy becomesoptimized for use in the liver, say, another can become optimized for use in thebrain or adapted for a novel purpose. In this way, the additional genes allow forincreased complexity and sophistication. As the genes take on divergent functions, they cease to be redundant. Often, however, while the genes acquire individually specialized roles, they also continue to perform some aspects of theiroriginal core function in parallel, redundantly. Mutation of a single gene thencauses a relatively minor abnormality that reveals only a part of the gene’sfunction (Figure 1–51). Families of genes with divergent but partly overlapping functions are a pervasive feature of vertebrate molecular biology, and theyare encountered repeatedly in this book.The Mouse Serves as a Model for MammalsMammals have typically three or four times as many genes as Drosophila, agenome that is 20 times larger, and millions or billions of times as many cells intheir adult bodies.
In terms of genome size and function, cell biology, andmolecular mechanisms, mammals are nevertheless a highly uniform group oforganisms. Even anatomically, the differences among mammals are chiefly amatter of size and proportions; it is hard to think of a human body part that doesnot have a counterpart in elephants and mice, and vice versa.
Evolution playsfreely with quantitative features, but it does not readily change the logic of thestructure.3940Chapter 1: Cells and Genomesgene G1gene G1gene G1gene G1gene Ggene G2ancestral organism(A)gene G2modern organismEVOLUTION BY GENE DUPLICATIONloss of gene G1(B)gene G2loss of gene G2gene G2loss of genes G1 and G2MUTANT PHENOTYPES OF MODERN ORGANISMFor a more exact measure of how closely mammalian species resemble oneanother genetically, we can compare the nucleotide sequences of corresponding(orthologous) genes, or the amino acid sequences of the proteins that thesegenes encode. The results for individual genes and proteins vary widely.
But typically, if we line up the amino acid sequence of a human protein with that of theorthologous protein from, say, an elephant, about 85% of the amino acids areidentical. A similar comparison between human and bird shows an amino acididentity of about 70%—twice as many differences, because the bird and themammalian lineages have had twice as long to diverge as those of the elephantand the human (Figure 1–52).The mouse, being small, hardy, and a rapid breeder, has become the foremost model organism for experimental studies of vertebrate molecular genetics.Many naturally occurring mutations are known, often mimicking the effects ofcorresponding mutations in humans (Figure 1–53).
Methods have been developed, moreover, to test the function of any chosen mouse gene, or of any noncoding portion of the mouse genome, by artificially creating mutations in it, aswe explain later in the book.One made-to-order mutant mouse can provide a wealth of information forthe cell biologist. It reveals the effects of the chosen mutation in a host of different contexts, simultaneously testing the action of the gene in all the differentkinds of cells in the body that could in principle be affected.Humans Report on Their Own PeculiaritiesAs humans, we have a special interest in the human genome.
We want to knowthe full set of parts from which we are made, and to discover how they work. Buteven if you were a mouse, preoccupied with the molecular biology of mice,humans would be attractive as model genetic organisms, because of one specialproperty: through medical examinations and self-reporting, we catalog our owngenetic (and other) disorders. The human population is enormous, consistingtoday of some 6 billion individuals, and this self-documenting property meansthat a huge database of information exists on human mutations.
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