Drosophila requires only 9 days to progress from a fertilized egg to an adult; it is vastly easier and cheaper to breed than any vertebrate, and its genome is much smaller—about 200 million nucleotide pairs, compared with 3200 million for a human. This genome codes for about 15,000 proteins, and mutants can now be obtained for essentially any gene. But there is also another, deeper reason why genetic 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 gene duplication, which is substantially greater in vertebrate genomes than in the fly genome and has probably been crucial in making vertebrates the complex and subtle creatures that they are.
The vertebrate Genome Is a Product of Repeated duplications
Almost every gene in the vertebrate genome has paralogs—other genes in the same 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 clusters present elsewhere in the genome, suggesting that genes have been duplicated in linked groups rather than as isolated individuals. According to one hypothesis, at an early stage in the evolution of the vertebrates, the entire genome underwent duplication twice in succession, giving rise to four copies of every gene.
The precise course of vertebrate genome evolution remains uncertain, because many further evolutionary changes have occurred since these ancient events.
Figure 1–40 Drosophila melanogaster.
molecular genetic studies on this fly have provided the main key to understanding how all animals develop from a fertilized egg into an adult. (From e.B. lewis, Science 221:cover, 1983. With permission from AAAs.)
Figure 1–41 Giant chromosomes from salivary gland cells of Drosophila.
Because many rounds of dnA replication have occurred without an intervening cell division, each of the chromosomes in these unusual cells contains over 1000 identical dnA molecules, all aligned in register. This makes them easy to see in the light microscope, where they display a characteristic and reproducible banding pattern. specific bands can be identified as the locations of specific genes: a mutant fly with a region of the banding pattern missing shows a phenotype reflecting loss of the genes in that region. Genes that are being transcribed at a high rate correspond to bands with a “puffed” appearance. The bands stained dark brown in the micrograph are sites where a particular regulatory protein is bound to the dnA. (courtesy of B. Zink and R. Paro, from
R. Paro, Trends Genet. 6:416–421, 1990. With permission from elsevier.)
Genes that were once identical have diverged; many of the gene copies have been lost through disruptive mutations; some have undergone further rounds of local duplication; and the genome, in each branch of the vertebrate family tree, has suffered repeated rearrangements, breaking up most of the original gene orderings. Comparison of the gene order in two related organisms, such as the human and the mouse, reveals that—on the time scale of vertebrate evolution—chromosomes frequently fuse and fragment to move large blocks of DNA sequence around. Indeed, it is possible, as discussed in Chapter 4, that the present state of 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 occur from 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 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 much DNA per cell; and