RE: GENETICS

From: Collins, Francis (NHGRI) (francisc@exchange.nih.gov)
Date: Sun Apr 07 2002 - 19:53:29 EDT

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    Hi Gordon,
            Sincere apologies to you and other ListServ members for my long
    silence. I got snowed under by a series of unplanned NIH events. I also
    got a bit overwhelmed with the volume of traffic on this Listserv -- but it
    is all very interesting. Regretfully, due to the unremitting press of other
    business, I won't be able to answer further queries after today.
            Now to your question: The stuff we have been calling "junk" is all
    of the nonconserved DNA in introns (the spacers in the midst of the coding
    regions) and in between genes. These regions are littered with repetitive
    sequences that appear hundreds or thousands of times in the genome. In the
    past, these have largely been considered as "selfish DNA" that is just hard
    to get rid of. The most abundant example is the so-called "Alu" sequence,
    of which we have about 1.5 million copies. This is a mobile element that
    still moves around occasionally (it has even caused the new appearance of
    cases of hemophilia by landing in the Factor VIII gene).
            When we were able to finally look at the entire human genome
    sequence, instead of bits and pieces, something interesting appeared. One
    can date the time at which a particular Alu sequence landed in the genome by
    how far it has subsequently diverged from the original parental sequence.
    Some Alus are only a few million years old. Others are much older. There
    is a gradual process of loss (by deletion) as well as the arrival of new
    elements by transposition. The surprise is that the older Alu elements are
    concentrated in the regions where genes are present at highest density. The
    most sensible conclusion is that these Alu elements actually provide some
    evolutionary advantage by being located near genes (as opposed to being in
    the gene "deserts", where no such selective retention is found). That
    doesn't sound so much like junk.
            One should not jump from this conclusion, however, to say that every
    base pair of the 3.1 million base pairs of the human genome has an important
    use. That will certainly not be the case (there are large segments of DNA
    that are deleted in some individuals, with no apparently consequence). But
    we would be wise not to throw the word "junk" around so loosely in the
    future.
            For more information on this, see International Human Genome
    Sequencing Consortium: "Initial sequencing and analysis of the human
    genome", Nature, February 2001.
            Regards,
            Francis
            

    -----Original Message-----
    From: gordon brown [mailto:gbrown@euclid.colorado.edu]
    Sent: Thursday, April 04, 2002 10:01 PM
    To: Collins, Francis (NHGRI)
    Subject: RE: GENETICS

    Dr. Collins,

    I hope this question is not too vague. (It is far removed from my field.)

    I seem to recall having read somewhere that at least some of what has been
    considered to be superfluous junk DNA may turn out to have a useful
    function. Can you comment on this?

    Gordon Brown
    Department of Mathematics
    University of Colorado
    Boulder, CO 80309-0395



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