Finding the male-determining genes has not been easy. One editor (1991) actually wrote, “The search for TDF has been a long and hard one.” The first three editions of this textbook show the incredibly interesting history of sex determination research, as new molecular technologies permitted new types of experiments.
In the first edition of the book (Gilbert 1985), the sex-determining gene was postulated to be a cell membrane factor called the H-Y antigen. It was acknowledged to be a controversial assignment, s its structure was unknown, and it was identified by antisera that female mice made against male cells. It was one of the first factors thought to be encoded by the Y chromosome. Moreover, if ovaries and testes cells were separately dissociated and allowed to re-associate, the testes would form tubules and the ovaries would form follicle-like structures. However, if the H-Y antigen were blocked on the re-aggregating testes cells, the testes structures failed to form, and the cells formed follicle-like structures (Ohno et al 1978, 1979; Zenzes et al 1978). The receptor for the H-Y antigen was found on gonadal cells of both sexes (Nagai et al 1979).
By the second edition of the book (1988), this view had been supplanted by the findings of David Page (1986, 1987) that there was a region of the Y chromosome that was present in XY males, absent in XX females, and missing in XY females, but present in XX males. This DNA region was located at the tip of the short arm of the Y chromosome. Moreover, there was a DNA sequence in this region that appeared to encode for a 404-amino acid zinc-finger transcription factor. This gene was called ZFY (Zinc-finger, Y-chromosome).
Page (1988) maintained that until they knew its sequence and function, it was “premature” to call ZFY the testis-determining factor, and noted that the DNA region defined by the translocated chromosomes was big enough for more than one protein-encoding gene (and that his interpretations could be wrong if there were rare double translocations.)
And he was correct. As molecular biology allowed scientists to look at progressively smaller regions, Sinclair and others (1990) showed that the testis-determining factor was not ZFY, but a nearby gene, which was called SRY (ex-determining region of the Y chromosome.) Anne McLaren (1990) illustrated the progressive winnowing of the genome to find the testis-determining factor
The author of the textbook heard about the SRY story from Albert de la Chappelle during dinner at a meeting of the Sigrid Juselius Conference in Helsinki in the summer of 1990. The text of the book was just being finished then.
Editorial comment 1991. Growth, Genetics, and Hormones 7. https://archive.org/stream/growthgeneticsho07unse/growthgeneticsho07unse_djvu.txt
Gilbert, S. F. Developmental Biology, Sinauer Associates, Sunderland, MA 1st ed: 1985; 2nd ed: 1998; 3rd ed: 1991.
Nagai Y, Ciccarese S, Ohno S. 1979. The identification of human H-Y antigen and testicular transformation induced by its interaction with the receptor site of bovine fetal ovarian cells. Differentiation. 13: 155- 164.
Ohno, S. 1979. Major Sex-Determining Genes. Springer-Verlag, New York.
Ohno S, Nagai Y, Ciccarese S. 1978. Testicular cells lysostripped of H-Y antigen organize ovarian follicle-like aggregates. Cytogenet Cell Genet. 20: 351- 364.
Page, D. C. 1986. Sex-reversal: Deletion mapping of the male-determining function of the human Y chromosome. Cold Spring Harbor Symp. Quant. Biol. 51: 229-235
Page, D. C. 1988. Is ZFY the sex-determining gene on the human Y chromosome? Philos Trans R Soc Lond B Biol Sci. 322: 155- 157.
Page DC, Mosher R, Simpson EM, Fisher EM, Mardon G, Pollack J, McGillivray B, de la Chapelle A, Brown LG. 1987. The sex-determining region of the human Y chromosome encodes a finger protein. Cell 51: 1091-1104.
Zenzes MT, Wolf U, Günther E, Engel W. 1978. Studies on the function of H-Y antigen: dissociation and reorganization experiments on rat gonadal tissue. Cytogenet Cell Genet. 20: 365- 372.