The Imprinted Brain

How genes set the balance between autism and psychosis

What Determines Sex?

Biological sex-determination is more complicated than it seems

Teaching a summer school course on evolutionary genetics and its social implications to students from all over the world is instructive in many ways. One of the most striking has been to make me aware of common misconceptions about sex-determination. Many students seem to think that biologically sex is simple: it’s determined by the father’s sperm. An X-sex-chromosome-bearing sperm fertilizes an always-X-carrying-egg to make it female (XX), a Y-bearing one makes it male (XY).

The truth, however, is more complicated and more intriguing. One problem is the fact that the Y-chromosome is tiny by comparison with the X and only produces 20-odd proteins, mostly concerned with highly male-specific functions like sperm-production. The X, by contrast, has almost 1200 genes, with at least 150 implicated in intelligence and cognition. Look at it this way: if all the genes for being male were on the Y, no woman could ever have a beard! But because hardly any genes related to maleness are on the  male chromosome, the vast majority must be on autosomes (the 22 non-sex chromosomes) or the X, which are of course carried by females. Such masculinizing genes could easily be turned on accidentally, explaining—and indeed predicting—bearded ladies.

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But this is just the start of it. Because X-chromosome genes spend twice as much of their evolutionary history riding in female bodies rather than male ones (because mammalian females have two Xs and males only one), X-chromosome genes are selected to benefit females twice as often as they are selected to benefit males. Indeed, if an X-gene conferred at least twice as much benefit to a woman’s reproductive success as it inflicted costs on a male carrier’s, natural selection could not fix it. For example, there is now good evidence for genes on the X that increase the fecundity of their female carriers but make their male carriers homosexual. To the extent that such homosexual males may be feminized, the evolutionary insight explains the apparent paradox: sex-chromosome genes can be in conflict, and what is good for one sex is not necessarily good for the other.

The most striking case is DAX1: a gene named after a Star Trek character. This is an X-chromosome gene that competes for control of sexual development with SRY, the male Y-chromosome sex-determining gene in mammals (which develop as females if SRY is not expressed). Duplication of DAX1 makes XY males develop as females and it has been described as an “anti-testis” rather than “pro-ovary” gene.

But that’s not all. According to a provocative theory proposed by Valerie Grant, the mother may also play a critical role in determining which kind of sperm—X- or Y-carrying—she allows to fertilize her. According to her theory, more dominant women with higher levels of testosterone are more likely to conceive sons, and less dominant ones with lower levels, daughters. Although the details remain controversial, the idea is a sound one. Contrary to what many people think, biological sex-determination is not simple and does not necessarily put one sex or the other in charge. The truth is that evolution is ultimately a question of some genes getting into the future at the expense of others, and consequently genetic conflict, not simple sex-chromosome determinism, is what explains sex-determination. Indeed, as I argue in The Imprinted Brain, genetic conflicts—including those related to sex-determination—almost certainly explain both mental health and illness—and arguably do explain the striking sex differences in the incidence of psychiatric illness. At the very least, these evolutionary and genetic insights give the lie to the common belief that biological sex-determination is crude and simple, and that it predicts clear-cut sex differences.

 

Christopher Robert Badcock, Ph.D., is author of The Imprinted Brain: how genes set the balance between autism and psychosis. 

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