Das gerissene Y.

das gerissen Y

aus: New York Times, September 14, 2009

New Clues to Sex Anomalies in How Y Chromosomes Are Copied


The first words ever spoken, so fable holds, were a palindrome and an introduction: “Madam, I’m Adam.”

A few years ago palindromes — phrases that read the same backward as forward — turned out to be an essential protective feature of Adam’s Y, the male-determining chromosome that all living men have inherited from a single individual who lived some 60,000 years ago. Each man carries a Y from his father and an X chromosome from his mother. Women have two X chromosomes, one from each parent.

The new twist in the story is the discovery that the palindrome system has a simple weakness, one that explains a wide range of sex anomalies from feminization to sex reversal similar to Turner’s syndrome, the condition of women who carry only one X chromosome.

The palindromes were discovered in 2003 when the Y chromosome’s sequence of bases, represented by the familiar letters G, C, T and A, was first worked out by David C. Page of the Whitehead Institute in Cambridge, Mass., and colleagues at the DNA sequencing center at Washington University School of Medicine in St. Louis.


They came as a total surprise but one that immediately explained a serious evolutionary puzzle, that of how the genes on the Y chromosome are protected from crippling mutations.

Unlike the other chromosomes, which can repair one another because they come in pairs, one from each parent, the Y has no evident backup system. Nature has prevented it from recombining with its partner, the X, except at its very tips, lest its male-determining gene should sneak into the X and cause genetic chaos.

Discovery of the palindromes explained how the Y chromosome has managed over evolutionary time to discard bad genes: it recombines with itself. Its essential genes are embedded in a series of eight giant palindromes, some up to three million DNA units in length. Each palindrome readily folds like a hairpin, bringing its two arms together. The cell’s DNA control machinery detects any difference between the two arms and can convert a mutation back to the correct sequence, saving the Y’s genes from mutational decay.

After Dr. Page discovered the palindromes, he wondered whether the system had weaknesses that might explain the male sex chromosome anomalies that are a major object of his studies. In the current issue of Cell, with Julian Lange and others, he describes what they call the “Achilles’ heel” of the Y chromosome and the wide variety of sexual disorders that it leads to.

The danger of the palindrome protection system occurs when a cell has duplicated all its chromosomes prior to cell division, and each pair is held together at a site called the centromere. Soon, the centromere will split, with each half and its chromosome tugged to opposite sides of the dividing cell.


Before the split, however, a serious error can occur. Palindromes on one Y chromosome can occasionally reach over and form a fatal attraction with the counterpart palindrome on its neighbor. The two Y’s fuse at the point of joining, and everything from the juncture to the end of the chromosome is lost

The double-Y’s so generated come in a range of lengths, depending on which of the palindromes makes the unintended liaison. Like other chromosomes, the Y has a left arm and a right arm with the centromere in between. The male-determining gene lies close to the end of the left arm. If the palindromes at the very end of the right arm make the join, a very long double-Y results in which the two centromeres are widely separated. But if the joining palindromes are just to the right of the centromere, a short double-Y is formed in which the two centromeres lie close together.

Dr. Page detected among his patients both short and long double-Y’s and those of all lengths in between. He and his colleagues then noticed a surprising difference in the patients’ sexual appearance that depended on the length between the centromeres of their double-Y’s.

japanische Haarnadel

The patients in whom the distance between the Y’s two centromeres is short are males. But the greater the distance between the centromeres, the more likely the patients are to be anatomically feminized. A few of the patients were so feminized that they had the symptoms of Turner’s syndrome, a condition in which women are born with a single X chromosome.

The explanation for this spectrum of results, in Dr. Page’s view, lies in how the double-Y’s are treated in dividing cells and in the consequences for determining the sex of the fetus.

When the centromeres are close together, they are seen as one and dragged to one side of the dividing cell. As long as the Y’s male-determining gene is active in the cells of the fetal sex tissue, or gonad, the gonads will turn into testes whose hormones will masculinize the rest of the body.

But when the centromeres lie far apart, chromosomal chaos results. During cell division, both centromeres are recognized by the cell division machinery, and in the tug of war the double-Y chromosome may sometimes survive and sometimes be broken and lost to the cell.

bewährtes Y

Such individuals can carry a mixture of cells, some of which carry a double-Y and some of which carry no Y chromosome. In the fetal gonads, that mixture of cells produces people of intermediate sex. In many of these cases the patients had been raised as female but had testicular tissue on one side of the body and ovarian tissue on the other.

In the extreme version of this process, the distribution of cells may be such that none of the fetal gonad cells possess a Y chromosome, even though other cells in the body may do so. Dr. Page and his colleagues found five of the feminized patients had symptoms typical of Turner’s syndrome. The patients had been brought to Dr. Page’s attention because their blood cells contained Y chromosomes. Evidently by the luck of the draw, the blood cell lineage had retained Y chromosomes but the all important fetal gonad cells had been denied them.

In 75 percent of women with Turner’s syndrome, the single X comes from the mother. “Since they are females, everyone imagines it’s Dad’s X that is missing,” Dr. Page said. “But it could easily be Dad’s Y.”

That the degree of feminization parallels the distance between the two centromeres of the double Y chromosome is “a fantastic experiment of nature,” Dr. Page said. Despite having studied the Y chromosome for nearly 30 years, he has learned that it is always full of surprises.

“I continue to see the Y as an infinitely rich national park where we go to see unusual things, and we are never disappointed,” he said.

Dr. Cynthia Morton, editor of the American Journal of Human Genetics, said the new explanation of Turner’s syndrome was plausible. “It’s another beautiful David Page contribution to the science of genetics,” Dr. Morton said.

das erwartungsfrohe Y


Mit andern Woten, männliche Selbstbehauptung ist mehr eine Kunst als ein Naturvorgang…


~ von Panther Ray - September 15, 2009.

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