By studying rare families in which a daughter shares the same Y chromosome as her father, scientists have determined that the pathway for male sexual development is not as consistent and robust as scientists have always assumed.
A team led by Michael Weiss, MD, PhD, and his colleagues at the university's School of Medicine, Case Western Reserve University, examined the function of the SRY gene.
This gene is responsible for initiating the process that leads to male development.
Weiss said that a general principle of developmental biology is that evolution favours reliability and 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.
The university's study employed 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 foetal 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.
The team decided to measure the biochemical threshold of the SRY master switch.
Weiss said that their expectation was that they'd find that a factor of 100 or more-a severe insult to the Y-encoded switch-was necessary to alter development but what they found was that the SRY threshold, as probed in father-daughter pairs, is only a factor of two.
The study has been published in the Proceedings of the National Academy of Sciences (PNAS).