Humans, like Drosophila, have XX-XY sex determination, but in humans, the presence of a gene (SRY) on the Y chromosome determines maleness. The phenotypes that result from abnormal numbers of sex chromosomes, which arise when the sex chromosomes do not segregate properly in meiosis or mitosis, illustrate the importance of the Y chromosome in human sex determination.

TURNER SYNDROME Persons who have Turner syndrome are female and often have underdeveloped secondary sex characteristics. This syndrome is seen in 1 of 3000 female births. Affected women are frequently short and have a low hairline, a relatively broad chest, and folds of skin on the neck. Their intelligence is usually normal. Most women who have Turner syndrome are sterile. In 1959, Charles Ford used new techniques to study human chromosomes, and discovered that cells from a 14-year-old girl with Turner syndrome had only a single X chromosome; this chromosome complement is usually referred to as XO.

There are no known cases in which a person is missing both X chromosomes, an indication that at least one X chromosome is necessary for human development. Presumably, embryos missing both Xs are spontaneously aborted in the early stages of development.

KLINEFELTER SYNDROME Persons who have Klinefelter syndrome, which has a frequency of about 1 in 1000 male births, have cells with one or more Y chromosomes and multiple X chromosomes. The cells of most males who have this condition are XXY, but cells of a few males with Klinefelter syndrome are XXXY, XXXXY, or XXYY. Persons with this condition are male and often have small testes and reduced facial and pubic hair. They are often taller than normal and sterile; most have normal intelligence.

POLY-X FEMALES In about 1 in 1000 female births, the infant’s cells possess three X chromosomes, a condition often referred to as triple-X syndrome. These persons have no distinctive features other than a tendency to be tall and thin. Although a few are sterile, many menstruate regularly and are fertile. The incidence of intellectual disability among triple-X females is slightly greater than that in the general population, but most XXX females have normal intelligence. Much rarer are females whose cells contain four or five X chromosomes. These women usually have normal female anatomy but are intellectually disabled and have a number of physical problems. The severity of intellectual disability increases as the number of X chromosomes increases beyond three.

XYY MALES Males with an extra Y chromosome (XYY) occur with a frequency of about 1 in 1000 male births. These individuals have no physical differences other than a tendency to be several inches taller than the average of XY males. Their IQ is usually within the normal range, although some studies suggest that learning difficulties may be more common than in XY males. The effect of the number of sex chromosomes on human development is summarized in Table 4.2.

THE MALE-DETERMINING GENE IN HUMANS The phenotypes associated with sex-chromosome anomalies show that the Y chromosome in humans, and all other mammals, is of paramount importance in producing a male phenotype. However, scientists have discovered a few rare XX males whose cells apparently lack a Y chromosome. For many years, these males presented an enigma: How could a male phenotype exist without a Y chromosome? Close examination eventually revealed a small part of the Y chromosome attached to another chromosome. This finding indicates that it is not the entire Y chromosome that determines maleness in humans; rather, it is a gene on the Y chromosome.

Early in development, all humans possess undifferentiated gonads and both male and female reproductive ducts. Then, about 6 weeks after fertilization, a gene on the Y chromosome becomes active. This gene causes the neutral gonads to develop into testes, which begin to secrete two hormones: testosterone and Mullerian-inhibiting substance. Testosterone induces the development of male characteristics, and Mullerian-inhibiting substance causes the degeneration of the female reproductive ducts. In the absence of this male-determining gene, the neutral gonads become ovaries, and female features develop.

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The male-determining gene in humans, called the sex-determining region Y (SRY) gene, was discovered in 1990 (Figure 4.6). This gene is found in XX males; it is also found on the Y chromosome of other mammals. Definitive proof that SRY is the male-determining gene came when scientists placed a copy of this gene in XX mice by means of genetic engineering. The XX mice that received this gene, although sterile, developed into anatomical males. Although SRY is the primary determinant of maleness in humans, other genes (some X linked, others Y linked, and still others autosomal) also play a role in fertility and the development of sexual phenotypes.