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16 The Seven Sexes of Humans In 1958, when I was a freshly minted PhD from Muller’s laboratory at Indiana University, I took my first academic job at Queen’s University in Kingston, Ontario. There, I was asked to teach a course in human genetics for medical students, which was a challenge because I had never had a human genetics course. As an offshoot from my dissertation study on the structure of the dumpy locus in fruit flies, I had published an article ontheparallelofthatgenecomplextotheRhbloodgroups.Thatwasmy only contact with human genetics. I spent a lot of time in the library at IndianaUniversity,andatQueen’sUniversitywhenIarrivedthere,reading what I could about human genetics, including Curt Stern’s pioneering text in this field.1 I hit the medical books and journals, looking for human parallels to genetic processes in fruit flies and other organisms. When I came to the topic of sex determination, I knew that fruit flies and humans both had XX female and XY male sex chromosomes. I read JonesandScott’sfinetextonhermaphroditicandpseudohermaphroditic disorders,anddippedintosomehumanembryologytextstofollowwhat wasthenknownaboutsexdifferentiationinhumans,bothinnormaland inclinicallyabnormalsexualdevelopment.2Iorganizedtheinformation in my mind and presented it in a series of lectures that I called, at the time, “the seven sexes of man.” Instead of thinking of sex as an all or none male or female classification , I thought of human sexuality as involving the coordination of several components:· Chromosomal sex Is it XX or XY?· Genetic sex Are there genes that determine sexual development? 112 The 7 Sexes· Gonadal sex Is the neutral gonad going to be a testis or an ovary?· Internal-genital sex Will the Wolffian ducts form the sperm transport system or degenerate? Will the Müllerian ducts form the uterus, oviducts, and upper vagina or will they degenerate?· External-genital sex Will the genital tubercle, folds, and swellings form a penis and scrotum or a clitoris and labia minora and majora?· Pubertal sex Will the child form female or male breasts, hair distribution and growth, and skeletal modification?· Psychological sex Will the orientation of the person be heterosexual, homosexual, or more complex?3 I pointed out to the class that our legal sex was a cultural rather than a biological assignment that was put on our birth certificate, usually within a month of our birth. I also pointed out to the class departures or inconsistencies between what nature provides and what society demands out of religious, philosophic, cultural, or legal traditions. At the time that I was in Canada, human sex chromosome nondisjunction was unknown. When I considered it, I thought like a fruit-fly geneticist, looked for parallels with fruit flies, and reasoned (incorrectly) that XO humans would be sterile males, and that XXY humans would be fertile females and thus not show up. I also wondered what was going on with Klinefelter males being chromatin positive, and Turner females being sex-chromatin negative. At that time, Murray Barr had not suggested this was an X-inactivation process; that came with Mary Lyon’s proposal that dosage compensation in mammals is X-inactivation of one of the two X chromosomes. I used the seven-sexes lectures later, in my genetics classes at UCLA, and in my non-majors biology class at Stony Brook University. It was a good way for students to see the interplay of genes, embryology, hormones, and the way a life cycle unfolds for one particular organ system. Chromosomal Sex We have already discussed the basic human sex-determining mechanism , which asserts that 46,XX is female and 46,XY is male. This means The Seven Sexes of Humans 113 that sex is determined at fertilization; more specifically, it is determined by the sperm, the male’s sperm being either X-bearing to produce future daughters or Y-bearing to produce future sons. About 99 percent of human births will be XX females or XY males. Genetic Sex Thereareabout19,000–23,000genesinhumans,dependingonhowthey are assigned genic status. Very likely, the reproductive system involves about 1000 of them. Some are involved early in determining whether the neutral gonads will be testes or ovaries. Once that is determined, there are genes that involve the hormones, such as steroid production and steroid receptors on target tissues; there are genes involving the manufacture of the sperm transport system or the female reproductive tract of oviducts, uterus, and vagina; there are genes involved in the differentiation of the male and female external genitalia; and there are genes involved in bone growth, breast development, body fat distribution , hair growth and distribution, muscle...


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