From: Chris Taylor (Christopher.Taylor@man.ac.uk)
Date: Thu 19 Jun 2003 - 13:18:32 GMT
WOW!!!
Cheers Wade that is fantastic :)
Wade T. Smith wrote:
> June 19, 2003
>
> Y Chromosome Depends on Itself to Survive
>
> By NICHOLAS WADE
>
> http://www.nytimes.com/2003/06/19/science/
> 19GENE.html?pagewanted=print&position=
>
> Biologists have made a fundamental discovery about how the human Y
> chromosome, a genetic package inherited by men, protects itself against
> evolutionary decay.
>
> As part of the work, the scientists have tallied the exact number of
> genes on the Y chromosome, finding more than they had expected. That
> and other research has led the researchers to assess the genetic
> differences between men and women as being considerably greater than
> thought.
>
> Although most men are unaware of the peril, the Y chromosome has been
> shedding genes furiously over the course of evolutionary time, and it
> is now a fraction the size of its partner, the X chromosome. Sex in
> humans is determined by the fact that men have an X and a Y chromosome
> in each of their body's cells. Women have a pair of X's.
>
> The decay of the Y stems from the fact that it is forbidden to enjoy
> the principal advantage of sex, which is, of course, for each member of
> a pair of chromosomes to swap matching pieces of DNA with its partner.
>
> The swapping procedure, known to biologists as recombination, occurs
> between the chromosomes inherited from the mother's and the father's
> side as a first step to produce the eggs or sperm. Not only does that
> swapping create novel combinations of genes, making each individual
> different, but it also enables bad genes — those damaged by mutation or
> DNA changes — to be replaced by their good counterparts on the other
> chromosome.
>
> Nature has barred the Y chromosome from recombining with the X, except
> at its very tips, because otherwise the male-determining gene, carried
> on the Y chromosome, would sneak into the X, making everyone male.
>
> The cost of this abstinence, however, is that most of the Y's genes
> have been rendered useless by mutation and physically shed. The X and
> the Y chromosomes were once as similar as the 22 other pairs of human
> chromosomes, and each carried about 1,000 genes. Now the Y carries
> fewer than 100. What prevents it losing even those?
>
> A team of researchers led by Dr. David C. Page, a biologist at the
> Whitehead Institute in Cambridge, Mass., has made a startling
> discovery. Denied the benefits of recombining with the X, the Y
> recombines with itself.
>
> The Y chromosome is made of a single DNA molecule that is 51 million
> units of DNA in length. Within the chromosome, Dr. Page and his
> colleagues report in Nature today, lie eight vast palindromes, regions
> that carry identical sequences of DNA units that run in opposite
> directions like the letters in the sentence "Madam, I'm Adam."
>
> By making a hairpin bend in the middle of a palindrome, the two arms
> can be brought together, aligning two long stretches of almost
> identical DNA sequence. That is the same step that precedes
> recombination between the maternal and paternal members of each
> ordinary chromosome pair, which also have almost identical sequences.
>
> In the case of the Y, the alignment of the palindromic sequences leads
> to gene conversion. A mutated gene on one arm of the palindrome can be
> converted to the undamaged sequence preserved on the other arm.
>
> This narcissistic process of salvation by palindrome seems to be what
> has saved men from extinction so far. It serves at least to
> counterbalance the decay caused by the lack of recombination. But Dr.
> Page and others say it is too soon to say which force is now uppermost.
>
> "This is a pretty striking result," said Dr. William Rice, an expert on
> the evolution of the sex chromosomes at the University of California at
> Santa Barbara.
>
> The mechanism, Dr. Rice said, is novel in human biology. It will take
> more study, he added, to see whether it can reverse Muller's Ratchet,
> the name that geneticists give to the grim process of irreversible
> genetic decay that affects asexual organisms and nonrecombining genome
> parts like the Y chromosome.
>
> "This changes our view of the Y as being an X chromosome wannabe," said
> Dr. Evan Eichler, an expert on chromosome structure at Case Western
> Reserve.
>
> The X chromosome, too, is denied the benefits of recombination when
> paired with the Y. But an X chromosome spends two-thirds of its time in
> a woman, where it can recombine with another X, dodging the Muller's
> Ratchet that has so eroded the Y.
>
> The palindromes that make gene conversion possible sometimes foster
> another result, large deletions of DNA, including the genes that they
> carry. Those losses are a major cause of male infertility, Dr. Page has
> found.
>
> Dr. Page's discovery is a fruit of a collaboration with the genome
> sequencing center at the Washington University School of Medicine in
> St. Louis. Under its previous director, Dr. Robert H. Waterston, and
> his successor, Dr. Richard K. Wilson, the center decoded the precise
> DNA sequence in the Y chromosome, a two-year effort.
>
> Dr. Huntington Willard, a genome expert at Duke, said the sequencing
> effort was "nearly heroic."
>
> "Most people," Dr. Willard said, "would have thrown their hands in the
> air and said this is too much like heavy lifting."
>
> Although most of the human genome was decoded using DNA from several
> people, the Y had to be decoded from one man, because the natural
> variation between two men would have swamped the very small differences
> in the arms of the Y's palindromic DNA.
>
> The donor of this Y chromosome is anonymous and designated by a sample
> number. But it is known that he was recruited locally by the Roswell
> Park Cancer Institute in Buffalo. So it can only be said that the
> person who revealed the secret of male survival is a Buffalo man known
> to science as Mr. RPCI-11.
>
> In the course of a long study of the Y chromosome, Dr. Page's team has
> now tallied that it contains 78 genes, some concerned with male
> fertility and sperm production and others with general biological
> functions. The fertility genes are almost all sited in the palindromic
> regions of DNA. Dr. Page theorizes that the other genes are on their
> way out or that the damage from failure to recombine may drop off after
> just a handful of genes is left.
>
> The finding of 78 active genes on the Y contradicts an earlier
> impression of the chromosome as being a genetic wasteland apart from
> its male-determining gene. But if the Y is not a wasteland, important
> consequences ensue for the differences between men and women.
>
> As often noted, the genomes of humans and chimpanzees are 98.5 percent
> identical, when each of their three billion DNA units are compared. But
> what of men and women, who have different chromosomes?
>
> Until now, biologists have said that makes no difference, because there
> are almost no genes on the Y, and in women one of the two X chromosomes
> is inactivated, so that both men and women have one working X chromosome.
>
> But researchers have recently found that several hundred genes on the X
> escape inactivation. Taking those genes into account along with the new
> tally of Y genes gives this result: Men and women differ by 1 to 2
> percent of their genomes, Dr. Page said, which is the same as the
> difference between a man and a male chimpanzee or between a woman and a
> female chimpanzee.
>
> Almost all male-female differences, whether in cognition, behavior,
> anatomy or susceptibility to disease, have usually been attributed to
> the sex hormones. But given the genomic differences that are now
> apparent, that premise has to be re-examined, in Dr. Page's view.
>
> "We all recite the mantra that we are 99 percent identical and take
> political comfort in it," Dr. Page said. "But the reality is that the
> genetic difference between males and females absolutely dwarfs all
> other differences in the human genome."
>
> Dr. Rice commented that he would have to think through this argument,
> noting that many genes - up to 15 percent in some animals - are more
> active in one sex than the other. These differences in gene activity
> might dwarf the genomic differences described by Dr. Page, he said.
>
> Another difference that has emerged between men and women concerns
> their ribosomes, the numerous small engines in the cell that build its
> working parts from the instructions in the genes. A general purpose
> gene on the Y makes a ribosome component. Its counterpart gene on the X
> makes a slightly different protein.
>
> That means that every ribosome in a man's body is slightly different
> from those in a woman's. Though the difference is pervasive, Dr. Page
> said, it was not known what significance it may have, if any.
>
> One thing his study had made him sure of was the complexity with which
> nature accomplishes its ends.
>
> "It's a great irony that though the Y has been called a sex
> chromosome," Dr. Page said, "the bulk of it is asexual. Nothing is as
> it appears."
>
> Copyright 2003 The New York Times Company
>
> ===============================================================
> This was distributed via the memetics list associated with the
> Journal of Memetics - Evolutionary Models of Information Transmission
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> see: http://www.cpm.mmu.ac.uk/jom-emit
>
-- ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Chris Taylor (chris@bioinf.man.ac.uk) http://pedro.man.ac.uk/ »people»chris ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ =============================================================== This was distributed via the memetics list associated with the Journal of Memetics - Evolutionary Models of Information Transmission For information about the journal and the list (e.g. unsubscribing) see: http://www.cpm.mmu.ac.uk/jom-emit
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