Geneticists have discovered a gene that determines the sex of a human embryo, a finding that offers an unprecedented window into the earliest stages of development.
The gene appears to start a complex chain reaction of hormones that eventually leads to the development of a male. Without the gene, the embryo begins a different pathway and grows into a female.
The gene is located on the Y chromosome, which is part of the inborn genetic code of men but not women. The researchers believe that a virtually identical gene determines sex in monkeys, dogs, cattle and all other mammals.
"This clearly is a landmark set of experiments," said Nobel laureate David Baltimore, director of the Whitehead Institute for Biomedical Research in Cambridge, Mass., where the gene was isolated.
For the first several weeks or so of development in the womb, all fetuses are sexually identical. They can grow to become either boys or girls. It is the newly discovered gene that seems to determine whether they will grow testes or ovaries and thus be male or female.
"The discovery should provide insight not only into why maleness develops, but into the process of development in general," said geneticist Robert Nussbaum of the University of Pennsylvania.
He said the new finding also could illuminate one of the most fundamental biological puzzles of our time: How unformed cells "differentiate" during the first seven weeks of gestation to form specialized organs such as the heart, muscles and brain.
Most researchers believe the process of development involves one or more genetic "master switches" that turn key genes on and off at appropriate times during gestation.
Scientists are eager to learn more about how such switches work also because some diseases, such as cancer, are caused by genes being turned on at the wrong times. Other diseases, such as inherited anemias, might be cured if a way could be found to turn on dormant genes.
New Areas of Investigation
"This (discovery) opens up whole new areas of investigation," said geneticist David C. Page of the Whitehead Institute, which is affiliated with MIT.
Page headed a team that reported the finding in a paper published today in the prestigious journal Cell.
His discovery may also provide better diagnosis, counseling, and therapy for individuals with currently untreatable chromosome abnormalities that render thousands of men and women infertile, he said in a telephone interview.
"This is a terribly important finding for biology," said geneticist Larry Shapiro of the UCLA School of Medicine.
The finding has no immediate practical application, such as for parents wishing to select the sex of an offspring or to learn the sex of a fetus.
Blueprint for the Body
The newly discovered gene is found on one of the sex chromosomes that were identified near the begining of this century. Scientists discovered then that each human cell has 23 pairs of chromosomes that are the blueprint for the body. Among these are the sex chromosomes, called X and Y.
At conception, each embryo gets an X chromosome from its mother and either an X or a Y chromosome from its father. In 1959, researchers discovered that the Y chromosome plays the critical role in sexual development: XX embryos are female, XY male.
But exceptions occur. Geneticists have found a small number of XY women and XX men. These otherwise normal individuals share one common trait--they are all infertile.
The researchers discovered the gene by analyzing deoxyribonucleic acid (DNA) from blood and skin cells from more than 100 men and women identified by fertility clinics as being XX males and XY females.
Using biotechnology techniques that have become common in this decade, the researchers compared microscopic fragments from the chromosomes of the study subjects to fragments of chromosomes from healthy people.
"This is a classic use of very rare human genetic defects to find out something important about human biology," said Baltimore.
Page and his colleagues, using this technique, last year discovered how such chromosome abnormalities occur.
Biologists have long known that, during the cell division that occurs in the formation of sperm, similar chromosomes--including the sex chromosomes--pair up and exchange genetic material. This mixing of genes makes possible an infinite variety of characteristics necessary for survival in a changing environment.
Page found that the sex abnormalities occur only when such an exchange involves a specific segment of the Y chromosome. He speculated that this segment contains a gene, called the testis determining factor, or TDF, that causes male gonads to be formed. The gonads, in turn, produce hormones that make the rest of the embryo male.
Using biotechnology techniques, Page's group chopped DNA from the sex chromosomes of the 100 human subjects into short fragments and looked for a fragment that was present in men and missing in women.