Gender divide: gene expression differs in males and females.

There are far more biological differences between males and females than meet the naked eye. A new study suggests that the two sexes vary in the amounts of proteins produced by thousands of genes--information that could explain why some diseases strike men and women differently.

"We're certainly conscious that sex can have an effect on numerous diseases," says Thomas Drake of the University of California, Los Angeles. For example, he points out, autoimmune diseases such as lupus disproportionately strike women, whereas men are more likely to have autism and some other mental disorders.

Ongoing studies by Drake and his colleagues are investigating the root causes of diabetes, obesity, and related metabolic diseases. To see how gender interacts with genetics to affect those diseases, Drake and his colleagues worked with 165 male and 169 female mice. Using samples of four tissues--liver, fat, muscle, and brain--the researchers measured production of the proteins encoded by each of 23,000 of the animals' genes.

"We were immediately struck by the differences in gender" Drake says. "They went way beyond what we were expecting."

The team found that in liver, fat, and muscle tissue, males and females differently expressed 55 to 72 percent of the genes studied. The brain had the smallest differences in gene expression between the sexes, occurring in only about 15 percent of the genes.

Next, the researchers looked to see whether the sex differences turned up primarily among maintenance genes, which keep up cells' general functions, or among genes that contribute to each organ's specific role. Drake says that he and his team were surprised to find that the majority of the differing genes control specific organ functions, for example, genes that metabolize drugs in the liver and those that direct energy storage in fat cells.

The researchers say in the August Genome Research that the mechanism behind sex differences in gene expression isn't yet clear. However, Drake notes, follow-up studies in his lab hint that sex hormones such as estrogen and testosterone control expression of many of the genes. When he and his colleagues removed mouse ovaries and testes, which produce these hormones, gender differences for many of the genes disappeared.

"This is a very nicely done study that shows the power of modern genetics," says Diane M. Robins of the University of Michigan in Ann Arbor. She points out that since mice and people share about 99 percent of their genes, future gene-expression studies could guide researchers in figuring out why men and women have different risks for some diseases. Further studies might also pinpoint the optimal doses of prescription drugs for men or women or assist researchers in crafting new, gender-specific medicines.