Edward Lambert, born in the 1700s in England, was to all appearances a normal boy until he entered puberty, whereupon his skin turned black and thickened, hardening into scales, solid like the shafts of feathers.
Edward and his father, who had the same condition, were by no means shy of their extraordinary looks. They exhibited themselves in London: “A man and his son, cover’d from head to foot with solid quills, except their face, the palms of their hands, and bottoms of their feet.”
Despite reports that the scales were so hard “that with the touch of a finger they make a sound like stones striking together,” the scaly men were sexually successful, fathering many children and grandchildren — who also grew up to develop scales.
The Royal Society at the time cited the Lamberts as proof of a trait that passes from father to son: In effect — and although no one knew it then — it was the beginning of work on the Y chromosome, the defining feature of men and the key to masculinity.
Unfortunately, scales turned up on girls in the Lambert family too, meaning that the genetic coding for the condition can not be found on the Y chromosome.
We all have two sex chromosomes, one from each parent. Women have two X chromosomes, men one X and one Y. Sperm carry either an X or a Y chromosome (along with the other 22 human chromosomes), and which type you get determines your sex.
From the erroneous start of research a few hundred years ago, this week in the journal Nature our knowledge of the human Y chromosome reaches a major milestone: A team of researchers based in the United States and the Netherlands have completed the detailed sequencing of the male sex chromosome.
In a commentary on the research, Huntington Willard of the Institute for Genome Sciences and Policy at Duke University in North Carolina, writes that “the accomplishment can only be described as heroic.”
Many cases of male infertility are due to genetic defects, and the Y sequence should give insights into their precise cause. But the sequencing feat is important in other ways, too.
The human sex chromosomes used to be just regular chromosomes, but they changed when sex determination evolved, around 300 million years ago. So the Y chromosome is an important evolutionary document of genetic change. The complete human genome has, of course, already been sequenced, but not all of it in detail. Many areas remain unknown.
“Piecing together these events [the evolutionary changes of the Y chromosome] remains a worthwhile challenge, for among the flotsam and jetsam of each chromosome lie clues to our history,” said Willard.
The researchers, led by David Page of the Whitehead Institute at the Massachusetts Institute of Technology, discovered that about 95 percent of the Y chromosome is totally isolated from its partner, the X chromosome. When sperm is made, all the chromosomes exchange DNA with their partners — except the Y chromosome.
At the end of the Y there is a short region of DNA that is the same as that in the same position on the X chromosome. This part, just 5 percent of the chromosome, does swap, but the overwhelming majority — the other 95 percent — of the Y is specific to males.
This region, which the researchers call the MSY (the “male-specific region of the Y”) is 23 million base pairs (DNA letters) long. None of the MSY is swapped with the X chromosome when sperm and eggs are made.
Page and colleagues have identified 78 genes in the MSY. Some genes are switched on throughout the body’s cells, whereas others are active only in the testes.
And like the rest of the human genome, much of the Y chromosome is taken up with repetitive DNA sequences. Many such sequences are palindromes, the DNA equivalent of the sentence “Madam, I’m Adam,” which reads the same from either the left or right. Genetic palindromes, however, are often millions of letters long.
In the MSY, there are palindromic areas 5.4 million base pairs long. But hidden within these areas are genes that are active in the testes — genes that are clearly very important to men.
In other chromosomes, the swapping of DNA when sperm and eggs are made help purge mistakes and mutations that build up. Geneticists call this swapping “recombination,” and without it chromosomes can become completely clogged with genetic junk.
The puzzle was, how does the Y chromosome avoid this without recombination?
Page and colleagues discovered that the Y chromosome swaps DNA with itself. The repetitive sequences exchange DNA between the two arms of the chromosome. This happens at an astonishingly high rate: The difference between a man’s Y chromosome and his father’s averages about 600 base pairs.
“Even the most repetitive and seemingly impenetrable stretches of the genome hold secrets that justify the effort,” says Willard. “Each chromosome has its own story to tell, quite apart from the story of the genome as a whole.”
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