"This is the first time that it has been shown that a retrogene can have a dramatic effect on fertility," said Dr. Colin E. Bishop, BCM professor of obstetrics and gynecology and molecular and human genetics. Dr. Jan, assistant professor in the department of obstetrics and gynecology at BCM, was his colleague in the research.
Such events, which are quite rare, start when the gene copies itself into RNA and then, via an enzyme called reverse transcriptase, back to DNA. Like transposons ("jumping DNA"), the copy inserts itself into a new part of the genome. In doing this, it can aquire new functions over time or even make nearby genes more or less active.
In this case, the retrogene involved is called mUtp14b, which when mutated results in the infertile mouse known as "juvenile spermatogonial depletion" (jsd). Young mice with this problem make sperm once but never again, resulting in sterility.
The gene that causes this odd reproductive abnormality is found in the intron (a non-coding portion of DNA) of another gene which has nothing to do with spermatogenesis.
"The gene is part of a series of genes we call retrogenes," said Bishop.
They later found that it originated from another gene on the X chromosome. That gene is active in all body tissues, but the retrogene is active only in the testes.
"A retrogene has jumped from the X chromosome," said Bishop.
The main theory is that during the cell's meiosis or reproduction, the X and Y chromosomes are inactivated. If genes on the X chromosome are needed for the production of sperm, then it would advantageous for that gene to exist elsewhere in the genome, said Bishop.
The specific gene has a role in making ribosomes, which are the protein manufacturers of the cells.
Currently, Bishop is evaluating records of infertile men to determine if this "jumping gene" plays a role in their reproductive problems.
Journal
Proceedings of the National Academy of Sciences