The idea that men and women are fundamentally different from each other is widely accepted. And throughout the world, this has created distinct ideas about which social and physical characteristics are necessary in each gender to maintain healthy human development.
However, social revolutions throughout the last century have challenged traditional ideas about not only which traits are normal and necessary for survival, but also how humans acquire them. Thanks to a new study from researchers at Case Western Reserve University, science is continuing the charge.
By studying rare families in which a daughter shares the same Y chromosome as her father, Michael Weiss, MD, PhD, and his colleagues at the university's School of Medicine have determined that the pathway for male sexual development is not as consistent and robust as scientists have always assumed.
A team led by Weiss, chairman of the Department of Biochemistry, the Cowan-Blum Professor of Cancer Research, and a professor of biochemistry and medicine, has published a study in the Proceedings of the National Academy of Sciences that examines the function of the SRY gene. This gene is responsible for initiating the process that leads to male development.
"A general principle of developmental biology is that evolution favors reliability," Weiss explained. "Robust switches ensure that our genetic programs give rise to a consistent body plan to ensure that babies have one heart, two arms, ten fingers, and so forth."
Traditional viewpoints emphasize the uniformity of this process. The new research indicates that male sexual development is less stable than other genetic programs.
In fetal development, a gene located on the Y chromosome, called SRY, begins the process that leads to male development. All fetuses initially develop with female tissues, no matter what the sex will be at birth, so the master switch is responsible for initiating the transformation of female tissues into male tissues. From there, the testes develop and produce testosterone, which eventually forms the male's external genitalia.
The university's study employs mutated SRY genes shared by a father and a sterile XY daughter. Females usually develop with an XX pair, but, in these families, the father instead produced a daughter with an XY pair. This occurs during fetal development when the SRY gene's master switch fails to trigger. Internal female tissues, such as the uterus and fallopian tubes, continue to develop but are dysfunctional and infertile.
"Yet the father has the same Y chromosome and the same mutation as the daughter," Weiss pointed out. "And since he is a fertile male, we know that the switch must be poised right at its edge."
The team decided to measure the biochemical threshold of the SRY master switch.
"Our expectation was that we'd find that a factor of 100 or more-a severe insult to the Y-encoded switch-was necessary to alter development," Weiss said. "But what we found was that the SRY threshold, as probed in father-daughter pairs, is only a factor of two."
Therefore, human males actually develop near the edge of sexual ambiguity. This means that, unlike the robust genetic programs which develop other essential processes like heart function, the SRY gene master switch is particularly vulnerable to change. It only takes a slight deviation from the normal process to dramatically alter fetal sexual development.