Morgan’s original experiments indicated that the white-eye mutation showed a pattern of inheritance like that expected of the X chromosome. However, it was one of Morgan’s students who showed experimentally that the white-eye mutation was actually a physical part of the X chromosome. Today, it seems obvious that genes are in chromosomes because we know that genes consist of DNA and that DNA in the nucleus is found in chromosomes. But in 1916, when Calvin B. Bridges, who had joined Morgan’s laboratory as a freshman, was working on his PhD research under Morgan’s direction, neither the chemical nature of the gene nor the chemical composition of chromosomes was known.

In one set of experiments, Bridges crossed mutant white-eyed females with wild-type red-eyed males (Fig. 17.6). Usually, the progeny consisted of red-eyed females and white-eyed males (Fig. 17.6a). This is the result expected when the X chromosomes in the mother separate normally at anaphase I in meiosis because all the daughters receive a w+-bearing X chromosome from their father and all the sons receive a w–-bearing X chromosome from their mother.

But Bridges noted a few rare exceptions among the progeny. He saw that about 1 offspring in 2000 from the cross was “exceptional”—either a female with white eyes or a male with red eyes. The exceptional females were fertile, and the exceptional males were sterile. To explain these exceptional progeny, Bridges proposed the hypothesis diagrammed in Fig. 17.6b: The X chromosomes in a female occasionally fail to separate in anaphase I in meiosis, and both X chromosomes go to the same pole. Recall from Chapter 15 that chromosomes sometimes fail to separate normally in meiosis, a process known as nondisjunction. Nondisjunction of X chromosomes results in eggs containing either two X chromosomes or no X chromosome. Figure 17.6b shows the implications for eye color in the progeny if the hypothesis is correct. The exceptional white-eyed females would contain two X chromosomes plus a Y chromosome (genotype w–/w–/Y), and the exceptional red-eyed males would contain a single X chromosome and no Y chromosome (genotype w+).

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Bridges’s hypothesis for the exceptional progeny in Fig. 17.6b was bold, as it assumed that Drosophila males could develop in the absence of a Y chromosome (XO embryos yielding sterile males, where “O” indicates absence of a chromosome), and that females could develop in the presence of a Y chromosome (XXY embryos yielding fertile females). The hypothesis was accurate as well as bold. Microscopic examination of the chromosomes in the exceptional fruit flies confirmed that the exceptional white-eyed females had XXY sex chromosomes and that the exceptional sterile red-eyed males had an X but no Y. Because fruit flies with three X chromosomes (XXX) or no X chromosome (OY) were never observed, Bridges concluded that embryos with these chromosomal constitutions are unable to survive. Bridges also conducted crosses that showed that nondisjunction can take place in males as well as in females. From the phenotypes of these exceptional fruit flies and their chromosome constitutions, Bridges concluded that the white-eye gene (and by implication any other X-linked gene) is physically present in the X chromosome.

Bridges’s demonstration that genes are present in chromosomes was also the first experimental evidence of nondisjunction. Drosophila differ from humans in that the Y chromosome is necessary for male fertility but not for male development. As we will see later in this chapter, a gene in the Y chromosome itself is the trigger for male development in humans and other mammals, and so for these organisms, the Y chromosome is needed both for male development and male fertility. Nondisjunction occasionally takes place in meiosis in humans as well as in fruit flies. When nondisjunction takes place in the human sex chromosomes, it results in chromosomal constitutions such as 47, XXY and 47, XYY males as well as 47, XXX and 45, X females. Nondisjunction of autosomes can also occur, resulting in fetuses that have extra copies or missing copies of entire chromosomes. The consequences of nondisjunction of human chromosomes were examined in Chapter 15.