Last January Harvard University president Lawrence Summers hypothesized that women may be innately less scientifically inclined than men. Not long after the ensuing uproar, researchers announced the sequencing of the human X chromosome. The project was hailed as a great leap forward in decoding the differences between men and women, at least from a biological perspective. While it did nothing to calm the maelstrom swirling around Summers, the new understanding of the chromosome revealed tantalizing clues to the role genes might play in shaping cognitive differences between the sexes. And while these differences seem to be largely to the female's advantage, permutations during the genetic recombination of the X chromosome may confer to a few men a substantial intellectual edge.
Considerations of this sort are mired in politics and sensationalism, but one fact is beyond dispute: Three hundred million years after parting ways in our earliest mammalian ancestors, the X and the Y chromosomes are very different genetic entities. The Y has been whittled down to genes governing a handful of functions, most entailing sperm production and other male-defining features. Meanwhile, the gene-rich X is the most intensely studied of the 23 chromosomes, largely because of its role in rendering men vulnerable to an estimated 300 genetic diseases and disorders associated with those mutations—from color blindness to muscular dystrophy to more than 200 brain disorders.
The sex chromosomes lay the foundation for human sexual difference, with women having two Xs, one from each parent, while men get an X from their mom and a Y from their dad. Only 54 of the 1,098 protein-coding genes on the X seem to have functional counterparts on the Y, a dichotomy that has led scientists to describe the Y chromosome as "eroded." This diminutive chromosome offers little protection against the slings and arrows of genetic happenstance. When an X-linked gene mutates in a woman, a backup gene on the second X chromosome can fill the gap. But when an X-linked gene mutation occurs in a man, his Y stands idly by, like an onlooker at a train wreck.
The brain seems particularly vulnerable to X-linked malfunction. Physician and human geneticist Horst Hameister and his group at the University of Ulm in Germany recently found that more than 21 percent of all brain disabilities map to X-linked mutations. "These genes must determine some component of intelligence if changes in them damage intelligence," Hameister says.
Gillian Turner, professor of medical genetics at the University of Newcastle in Australia, agrees that the X chromosome is a natural home for genes that mold the mind. "If you are thinking of getting a gene quickly distributed through a population, it makes sense to have it on the X," she says. "And no human trait has evolved faster through history than intelligence."
The X chromosome provides an unusual system for transmitting genes between sexes across generations. Fathers pass down nearly their entire complement of X-linked genes to their daughters, and sons get their X-linked genes from their mothers.
Although this pattern of inheritance leaves men vulnerable to a host of X-linked disorders, Hameister contends that it also positions them to reap the rewards of rare, beneficial X-linked mutations, which may explain why men cluster at the ends of the intelligence spectrum. "Females tend to do better overall on IQ tests; they average out at about 100, while men average about 99," Hameister says. "Also, more men are mentally retarded. But when you look at IQs at 135 and above, you see more men."
To understand his hypothesis, consider that during the formation of a woman's eggs, paternal and maternal X chromosomes recombine during meiosis. Now suppose a mother passes to her son an X chromosome carrying a gene or genes for superintelligence. While this genetic parcel would boost the son's brilliance, he could pass that X chromosome only to a daughter, where it could be diluted by the maternally derived X. The daughter, in turn, could pass on only a broken-up and remixed version to the fourth generation, due, again, to the recombination that occurs during meiosis. Odds are that the suite of genes for superintelligence wouldn't survive intact in the remix. "It's like winning the lottery," Hameister adds. "You wouldn't expect to win twice in one day, would you?"
The theory is controversial. Among its detractors is David Page, interim director of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. "Many claims have been made about gene enrichment on the X, and most look quite soft to me," he says. Nonetheless, he says that the attempt to link the enrichment of cognitive genes on the X to IQ differences "is a reasonable speculation."
Intelligence is a multifaceted quality that is unlikely to be traced to a single gene. Yet the link between gender and cognition is far too persistent for the public—or science—to ignore. Until recently sex differences in intelligence were thought to result chiefly from hormones and environment. New findings suggest genes can play a far more direct role. Working constructively with that insight will be a delicate challenge for the new millennium, one perhaps best avoided by college presidents.
David Skuse, professor of behavioral and brain sciences at the Institute of Child Health in London, has shown how the X chromosome can influence social skills. In studies of women with only one X chromosome, he found that test subjects who inherited their X chromosome from their fathers had better social skills than those who inherited their X chromosome from their mothers. This disparity offers clues to why boys, who inherit their single X chromosome from their mothers, are more vulnerable to disorders that affect social functioning.
What does your research reveal?
S: Imprinted genes are expressed differently depending on whether they are inherited from the father or the mother. By comparing the cognitive social skills of women with a single X chromosome [Turner's syndrome]—which could be either maternal or paternal in origin—with the skills of normal women, who have an X chromosome from both parents, we were able to show that X-linked imprinted genes could influence sexually dimorphic traits. It is important to note a couple of things; first, the gene that is imprinted was not expressed in the parent from whom it was inherited, so girls do not get their social skills from their fathers in any simple sense. Second, we are talking about a mechanism that potentially affects every one of us, but its effects will be subtly different depending on our genetic makeup and our environment of rearing.
Have you looked at whether normal men and women differ in social cognition?
S: We did a study of normal males and females on skills such as the ability to tell whether someone is looking directly at you and interpreting facial expressions. We looked at 700 children and over 1,000 adults and discovered little difference between adult men and women. On the other hand, girls entering elementary school tend to do a much better job than boys in interpreting facial expressions. This difference almost completely disappears after puberty.
What are the implications of your work?
S: What I can say is that disorders of social cognitive skills seem to affect a surprisingly large number of people. The disability can lead, especially among boys, to disruptive behavior in childhood if it is not recognized and treated sufficiently early. Others have found that boys are more vulnerable than girls to the long-term impact of maltreatment in childhood, and the risk of such boys becoming antisocial in later life seems to be related to a gene on the X chromosome, although not one that is imprinted.