MRC National Institute for Medical Research, London
Science for Health
An unexpected role for the X chromosome in male fertility
06 May 2008
Spermatogenesis is the process in which stem cells in the testis divide and differentiate, eventually forming mature sperm. The genes carried on the X chromosome are inactive (''transcriptionally repressed'') during most of spermatogenesis, and the X chromosome was therefore thought to contain few genes functioning in male germ cell development.
James Turner (pictured) and his group in NIMR's Division of Stem Cell Biology and Developmental Genetics, has challenged this view in a recent paper in Nature Genetics. Using a bioinformatic approach they have found that around 273 of the 1500 or so protein-coding genes on the X chromosome are expressed only in males, and that this expression is restricted to the testis. More surprisingly, these genes are expressed specifically during the period when the X chromosome is in a largely inactive state.
So how could these genes evade the transcriptional repression that affects the X chromosome? The answer may lie in the finding that each gene family exists as multiple-copies, ranging in number from two to twenty-eight. James Turner said:
Gene amplification probably evolved at least in part to counteract the repressive chromatin environment on the X chromosome during spermatogenesis. The transcriptional repression of the X chromosome means that the level of expression from individual X-linked genes is very low. However, if you now have multiple copies of the same gene all expressing together, the resulting output is much higher.
Preliminary analysis suggests that the human X chromosome is also enriched in multiple-copy spermatogenesis genes. Therefore reduced copy number, which is likely to occur in some individuals, could predispose to infertility in men.
X chromosome map
Map of the X chromosome showing the position and copy number of testis-specific multi-copy genes.
Original article
The research findings are published in full in:
Jacob L Mueller, Shantha K Mahadevaiah, Peter J Park, Peter E Warburton, David C Page & James M A Turner. (2008)
The mouse X chromosome is enriched for multi-copy testis genes exhibiting post-meiotic expression.
Nature Genetics, epub ahead of print. Abstract
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