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The Fertility Show


 

'Female chromosome' might make a man a man

29 July 2013

By Clara Salice

Appeared in BioNews 715

The 'female' X chromosome has been shown to contain several genes that may be involved in sperm production. The finding, dubbed 'the double life of the X chromosome', means that what was previously believed to be the counterpart of the male-only Y chromosome may in fact play a role in male fertility.

The researchers also found an area of rapidly evolving genes on the X chromosome, challenging the longstanding belief that the sequence shows little variation among mammals.

'The X is the most famous, most intensely studied chromosome in all of human genetics', said Professor David Page, director of the Whitehead Institute in Cambridge, Massachusetts, who led the study. 'But there's another side to the X, a side that is rapidly evolving and seems to be attuned to the reproductive needs of males'.

The study, published in Nature Genetics, compared the genetic sequence of the mouse and human X chromosome. Although 95 percent of genes in the X chromosome are shared between mice and humans, the researchers identified 340 unshared genes. Most of these were found in palindromic regions of the chromosome, areas of 'mirror-image' genetic sequence that evade conventional sequencing.

Researchers at the Whitehead Institute used a technique, developed in collaboration with Washington University in St.Louis, called single-haplotype iterative mapping and sequencing (SHIMS). Page had used this technique previously to produce a definitive reference for the Y chromosome, reporting rapidly evolving genes in several regions of large palindromes.

The detailed sequencing method confirmed that most X-linked single-copy genes are shared by humans and mice and have remained stable, in accordance with Ohno's law dating back to research in the 1960s, but also showed that the newly identified genes were rapidly changing. The study showed that 10 percent of X chromosome genes in humans, and 16 percent in mice, have evolved since the two species shared a common ancestor 80 million years ago.

Dr Huntington Willard, a geneticist at Duke University who was not involved in the study, told The Scientist, 'Someday, this is destined to become, I guess, "Page's Law"'.

The newly identified X chromosome genes were not expressed in women and not associated with any X-linked phenotypes, but were mostly found in the testes region, leading the researchers to suspect a link with male fertility. 'The dynamism of these regions could underlie significant medical conditions such as infertility, poor sperm production, and even [testicular] cancer', said Page.

Dr Jacob Mueller, a postdoctoral researcher and first author of the paper, states that 'now that we're confident of the assembly and gene content of these highly repetitive regions on the X chromosome, we can start to dissect their biological significance'.

The X chromosome is known to cause several inherited diseases, such as colour-blindness and haemophilia. Page adds: 'There's a whole other book to be written about this aspect of the X'.

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