In their study of the fly, published in the January 15 issue of Human Molecular Genetics, the researchers focused on a gene that in male flies regulates meiosis, a key step in the creation of sperm and egg in all animals, including humans. In the male fly, loss of the gene, known as boule, leads to meiotic arrest, and hence infertility. Predictably, when the scientists inserted a normal copy of the gene into the flies, meiosis resumed. More notably, however, when they inserted the human form of boule, known as BOULE, into the meiosis-defective flies, development of the fly sperm also resumed.
The UCSF researchers had previously discovered the existence of BOULE in humans and had suggested that it was the distant relative of the fly boule gene, based on a similarity in the genes' protein sequences and gene expression patterns. This finding was significant in itself, as it illuminated an ancient genetic lineage tracing back through the mouse to the fly, which evolved 600 million years ago. But nothing was known about BOULE's function.
The new finding is the first demonstration that a human reproductive gene can "rescue" reproductive defects in the fly, and strongly suggests that the human gene BOULE also regulates meiosis in human sperm development, the researchers say. This is significant because some 30 percent of infertile men have meiotic arrest during sperm development.
"The identification of genes such as BOULE that are required for meiotic function are likely to be important clinically," says Eugene Yujun Xu, PhD, UCSF assistant research geneticist in the laboratory of senior author Renee A. Reij
Contact: Jennifer OBrien
University of California - San Francisco