| Issue 59 Contents |
Sex, Genes and Chromosomes: A Feminist View
Jennifer A. Marshall Graves
Of all the differences that distinguish people, the most obvious is whether they are male or female. It is surprising to find that all the items on the long list of differences in anatomy, physiology and behaviour between men and women are a direct or indirect result of just one gene. In this talk, I will describe this gene and the peculiarities of the Y chromosome on which it lies, talk about its evolutionary rise and predict its ultimate demise.
The decision of what sex a baby will develop as is made fairly late in development, when the undifferentiated gonad gets the message to form either a testis or an ovary. Testis is triggered by a gene called the testis determining factor (TDF) that we have always supposed activates a battery of other genes that differentiate a testis. If no testis determining signal is received, the gonad develops as an ovary. Sex determination really amounts to testis determination because everything else flows from this by a cascade of hormones unleashed by the differentiated gonad.
In man and other mammals, sex is decided by the chromosomes the embryo received from its parents. Females have two copies of a medium-sized chromosome called the X, while males have only a single X plus a smaller chromosome called the Y. We know that the Y chromosome bears a male-dominant sex determiner because if you have a Y you are male whatever your number of Xs.
A race to isolate TDF began with its localization on the Y, using DNA from people with only half a Y chromosome, or only a small bit of it to zero in on TDF. A candidate gene ZFY was claimed to fill the bill, but ultimately failed the test. The SRY gene was isolated a year later and shown to be the real TDF because it was mutated in females with a Y, and it produced males when injected into XX mouse embryos. Australia had a big part in this story, since the first inkling that ZFY was the wrong gene was our discovery that it was not on the Y in Australian mammals (marsupials and monotremes), and subsequently SRY was discovered and proved to be the right gene by two young Australians working in London.
The SRY gene, and indeed the entire Y chromosome, is very unusual. The Y is a small chromosome with hardly any genes on it. It is a real genetic wasteland, stuffed with dead virus genomes and repetitive sequences that do not make proteins. Whereas the X has about 1400 genes with all sorts of roles in metabolism and specialist functions having little to do with sex, the human Y has only 26 genes, and most of these are concerned with sex determination and differentiation, especially making sperm. This is even more peculiar when you understand that the Y arose as a degraded copy of the X, and many or most genes on the Y have copies on the X.
Why has the Y degraded to this sorry state? Acquiring a sex determining gene was the kiss of death for the Y. After this happened, other genes with an advantage in males began to accumulate around TDF, and it became an advantage for the region to become isolated from the constant genetic shuffling that keeps chromosomes in a pristine state. Without the possibillity of repair, genes were mutated, inactivated and ultimately deleted, and the Y was invaded by dead virus genomes.
Since the Y chromosome evolved by degradation of the X, the genes on the Y must have evolved from genes on the X. Of special interest is the gene, SOX3, from which the sex determining SRY evolved. SOX3 is active in the brain with a minor role in the developing testis. How did a respectable brain-determining gene become a testis-determining gene? The peculiar structure of the SRY gene and its lack of conservation makes it look as though the ancestral gene was chopped off, leaving only the part that binds to DNA. It may work, not as we had thought by turning on testis-differentiating genes, but by turning an inhibitor off - essentially by getting in its way.
We have always believed that the way that humans determine sex is shared at least with all vertebrates. This is wrong. Although the genetic pathway for making males seems to be much the same in humans, birds and even fish, the triggers that control the process seem to be extremely changeable. Studies with other mammals, as well as birds and reptiles, show that SRY is a real Johnny-come-lately, and the Y chromosome may have got its start from another ancient sex determining gene.
Even worse, the Y chromosome, and the sex determining gene it bears, has its use-by date. There are two rare eastern European rodents with no Y chromosome and no SRY gene. This shows what will happen ultimately to the human Y when it degrades completely and a new sex determining system takes over.
Abstract of a lecture given to the Royal Society of Victoria, 14 June 2001 and published with their permission. [www.sciencevictoria.org.au]
Professor Jennifer A. Marshall
Graves, PhD, FAA
Comparative Genomics Research Group
Research School of Biological Sciences
The Australian National University
Canberra, ACT 2601, Australia