An international team of gene scientists has unveiled the first complete analysis of the X chromosome, the secretive coil of DNA that shapes human gender and whose malfunctions are to blame for nearly 10 per cent of inherited diseases.
Their landmark work, published on Thursday in the weekly British science journal Nature, suggests that men and women owe their sex partly to chromosomes that evolved from a genderless organism less than 300 million years ago.
The study also opens up new paths for understanding sources of mental retardation and diagnosing — and later possibly curing — testicular cancer, immune system disorders and many other inherited ailments.
"The human X chromosome has a unique biology that was shaped by its evolution ... (and) holds a unique place in the history of medical genetics," says their paper.
In their set of 23 pairs of chromosomes, humans have a pair of gender chromosomes, each inherited from one of their biological parents. Women have two X chromosomes, so named because of their approximate shape, while men have an X and a Y.
The Y chromosome has steadily eroded to a little stump over the millennia, a process that holds out the intriguing theory that men may eventually be eliminated by evolutionary pressure.
The Y now has less than 100 genes, the stretches of DNA that encode proteins, the molecules that comprise and maintain human tissues.
In the latest study, a team led by the Wellcome Trust Sanger Institute in Cambridge, England, sequenced and analysed more than 99 per cent of the X chromosome, identifying a whopping tally of 1,098 genes on it, about four per cent of the total on the entire genome.
Seeking to understand this remarkable difference between X and Y, the team believes the two chromosomes evolved from humble beginnings as an "ordinary" pair of identical chromosomes in a sex-less organism.
Changes to a gene on one of the pair triggered the molecular cascade that led to male development, and set in train the degeneration of that chromosome to its present rump-like state.
X, though, has remained largely preserved over the millions of years. The theory is that it serves to maintain a fuller panoply of genes in order to offset the shrinking of the Y.
Out of 3,199 identified inherited diseases, 307 can be attributed to mutations, or flaws, on the X chromosome that disrupt vital protein-making machinery, the study says.
Many of these diseases, including haemophilia and Duchenne muscular dystrophy, have already been sourced to the X because they only occur among men. The reason for this is that men have only one copy of the X, whereas women have a backup copy, which means they are less exposed to that particular mutation risk.
But there are also many other rarer diseases that are common to both genders and can be attributed to X, the study says.
Already, thanks to the new sequence, 43 more genes have been named as the suspected culprits for conditions ranging from cleft palate and blindness to testicular cancer, a disregulation of the immune system called X-linked lymphoproliferative disease (XLP) and NS-LXMR, a form of mental retardation.
"From studying such genes, we can get remarkable insight into disease processes," said Mark Ross, project leader at the Wellcome Trust Sanger Institute.
"From our study of one gene involved in an X-linked disease, a genetic test was developed and a new pathway that controls the workings of the immune system was discovered."
Other members of the X team included the Baylor College of Medicine in Houston, Texas; the Max Planck Institute for Molecular Genetics and the Institute for Molecular Biotechnology in Germany; and the Washington University Genome Sequencing Center in St Louis, Missouri.
The study found that nearly a third of the entire X chromosome is taken up by a repetitive DNA sequence.
The theory is that this is a mechanism to "silence" genes, something that is especially important for females, for it ensures that unneeded genes on their backup copy of the X remain deactivated.