The presence of different numbers of X chromosomes in males and females presents a special problem in development. Because females have two copies of every X-linked gene and males possess one copy, the amount of gene product (protein) from X-linked genes would normally differ in the two sexes — females would produce twice as much gene product as males. This difference could be highly detrimental because protein concentration plays a critical role in development. Animals overcome this potential problem through dosage compensation, which equalizes the amount of protein produced by X-linked genes in the two sexes. In fruit flies, dosage compensation is achieved by a doubling of the activity of the genes on the X chromosome of the male. In the worm Caenorhabdi-tis elegans, it is achieved by a halving of the activity of genes on both of the X chromosomes in the female. Pla-
cental mammals use yet another mechanism of dosage compensation; genes on one of the X chromosomes in the female are completely inactivated.
In 1949, Murray Barr observed condensed, darkly staining bodies in the nuclei of cells from female cats ( FIGURE 4.17); this darkly staining structure became known as a Barr body. Mary Lyon proposed in 1961 that the Barr body was an inactive X chromosome; her hypothesis (now proved) has become known as the Lyon hypothesis. She suggested that, within each female cell, one of the two X chromosomes becomes inactive; which X chromosome is inactivated is random. If a cell contains more than two X chromosomes, all but one of them is inactivated. The number of Barr bodies present in human cells with different complements of sex chromosomes is shown in Table 4.2.
As a result of X inactivation, females are functionally hemizygous at the cellular level for X-linked genes. In females that are heterozygous at an X-linked locus, approximately 50% of the cells will express one allele and 50% will express the other allele; thus, in heterozygous females, proteins encoded by both alleles are produced, although not within the same cell. This functional hemizygosity means that cells in females are not identical with respect to the expression of the genes on the X chromosome; females are mosaics for the expression of X-linked genes.
X inactivation takes place relatively early in develop-ment—in humans, within the first few weeks of development. Once an X chromosome becomes inactive in a cell, it remains inactivated and is inactive in all somatic cells that descend from the cell. Thus, neighboring cells tend to have the same X chromosome inactivated, producing a patchy pattern (mosaic) for the expression of an X-linked characteristic in heterozygous females.
This patchy distribution can be seen in tortoiseshell cats ( Figure 4.18). Although many genes contribute to coat color and pattern in domestic cats, a single X-linked locus determines the presence of orange color. There are possible
4.17 A Barr body is an inactivated X chromosome. (a) Female cell with a Barr body (indicated by arrow). (b) Male cell without a Barr body. (Part a, George Wilder/Visuals Unlimited; part b, M. Abbey/Photo Researchers.)
Number of Barr bodies in human cells with different complements of sex chromosomes
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