S

(a) Bar region

Wild type B+B+

Heterozygous Bar B+B

Homozygous Bar BB

Heterozygous double Bar B+BD

I 9.7 The Bar phenotype in Drosophila melanogaster results from an X-linked duplication.

(a) Wild-type fruit flies have normal-size eyes. (b) Flies heterozygous and (c) homozygous for the Bar mutation have smaller, bar-shaped eyes. (d) Flies with double Bar have three copies of the duplication and much smaller bar-shaped eyes.

that one or both chromosomes loop and twist so that these regions are able to line up ( FIGURE 9.6b). The appearance of this characteristic loop structure during meiosis is one way to detect duplications.

Duplications may have major effects on the phenotype. In Drosophila melanogaster, for example, a Bar mutant has a reduced number of facets in the eye, making the eye smaller and bar shaped instead of oval ( FIGURE 9.7). The Bar mutant results from a small duplication on the X chromosome, which is inherited as an incompletely dominant, X-linked trait: heterozygous female flies have somewhat smaller eyes (the number of facets is reduced; see Figure 9.7b), whereas, in homozygous female and hemizygous male flies, the number of facets is greatly reduced (see Figure

9.7c). Occasionally, a fly carries three copies of the Bar duplication on its X chromosome; in such mutants, which are termed double Bar, the number of facets is extremely reduced (see Figure 9.7d). Bar arises from unequal crossing over, a duplication-generating process ( FIGURE 9.8; see also Figure 17.17).

How does a chromosome duplication alter the pheno-type? After all, gene sequences are not altered by duplications, and no genetic information is missing; the only change is the presence of additional copies of normal sequences. The answer to this question is not well understood, but the effects are most likely due to imbalances in the amounts of gene products (abnormal gene dosage). The amount of a particular protein synthesized by a cell is often directly related to the number of copies of its corresponding gene: an individual with three functional copies of a gene often produces 1.5 times as much of the protein encoded by that gene as that produced by an individual with two copies. Because developmental processes often require the interaction of many proteins, they may critically depend on the relative amounts of the proteins. If the amount of one protein increases while the amounts of others remain constant, problems can result ( FIGURE 9.9). Although duplications can have severe consequences when the precise balance of a gene product is critical to cell function, duplications have arisen frequently throughout the evolution of many eukary-otic organisms and are a source of new genes that may provide novel functions. Human phenotypes associated with some duplications are summarized in Table 9.1.

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