Variation in women’s X chromosomes may explain differences between sexes
March 17, 2005
The first comprehensive survey of gene activity in the X chromosomes of women has revealed an unexpected level of variation among individuals, according to new research. The results may have important implications for understanding the differences in traits among women and between males and females, in terms of both health and disease, said Dr. Huntington Willard, director of the Duke University Institute for Genome Sciences & Policy (IGSP) and the study’s senior author. The findings also offer new insight into the basis for well-established differences between the sexes, he said. Willard said that the extensive variation in gene activity in the sex chromosomes means that, in essence, there is not one human genome, but two male and female. We looked at the X chromosomes of 40 women and every one of them had a unique pattern of gene expression, Willard said. All of that variation is completely unique to women. The X chromosomes of males are all the same in this regard. Willard and study co-author Dr. Laura Carrel, of Pennsylvania State University, reported their findings in the March 17, 2005, issue of Nature. The National Institutes of Health supported the research. In the same issue of Nature, more than 250 researchers including Willard and Carrel, reported the complete DNA sequence of the human X chromosome. In animals, sexual identity is governed by sex chromosomes. In humans and other mammals, males have one X and one Y chromosome, while females have a pair of X’s. Many genes on the male Y chromosomes have been lost over evolutionary time, leaving the chromosome with fewer than 100 functional genes. In contrast, the X chromosome present in at least one copy in both sexes encodes more than 1,000 genes. More than 45 years ago, researchers discovered that genes on one copy of the female’s X chromosome are switched off, a modification known as X inactivation. Originally, scientists had assumed that the inactivation process resulted in complete silencing of the genes on the second X chromosome, Willard said, in order to leave both sexes with the same activity level of the genes encoded by the X chromosome. Scientists had also assumed that the X chromosomes in all women would be identical. The new work extends earlier findings, which revealed that individual women exhibit extensive differences among them with respect to X inactivation, Willard said. In their study, the researchers isolated cell lines from each of 40 women. They then measured the activity level of each of 471 genes to determine whether the second copy was turned on or off. Overall, about 15 percent of genes on the second X chromosome escape inactivation to some degree, they found. The proportion of genes that remain active differs dramatically among regions of the X chromosome, they reported. However these findings have immediate implications for individuals born with X chromosome abnormalities, Willard said. The findings also highlight key differences between female and male genomes. We now know that 25 percent of the X chromosome which consist of about 200 to 300 genes - can be uniquely expressed in one sex relative to the other, Willard said. In essence, therefore, there is not one human genome, but two male and female. Such characteristic genomic differences should be recognized as a potential factor to explain sex-specific traits both in complex disease, as well as normal gender differences, he said.
Source: Duke University