A 2.7 million year old human gene

From: Glenn Morton (glenn.morton@btinternet.com)
Date: Tue Aug 27 2002 - 00:27:29 EDT

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    I ran into a report on the National Geographic site discussing a new work on
    genetics of humans. The work is based upon the dating of a particular gene
    which works in apes but was deleted in the line leading to men. The NG site
    "The investigative work by the Varki team began several years ago. In 1998
    Varki and UCSD's Elaine Muchmore announced that they had identified the
    first major biochemical and genetic difference between humans and their
    closest evolutionary cousins, the great apes. The gene, a sialic acid which
    codes for the production of a cell-surface sugar called N-glycolylneuramine
    Acid (Neu5Gc), was mutated (knocked out) in humans in comparison with the
    normal, intact gene in apes. "

    What happened was that a mutation inactivated the CMAH gene which makes an
    enzyme used to manufacture N-Glycolylneuraminic acid (Neu5Gc). The workers
    looked for the gene in Neanderthal bones and found that while the
    neanderthal bones preserved similar chemicals, called sialic acids, they
    didn't contain any Neu5Gc. This means that Neanderthals were like us,
    lacking the Neu5Gc and thus most likely lacking the CMAH gene. This means
    that the mutation inactivating CMAH occurred prior to the common ancestor of
    Neanderthals and modern humans 5-600,000 years ago. Humans have a pseudogene
    for CMAH which has multiple variants in the population. THese variants can
    be used to calculate how long it would take the pseudogene to accumulate the
    observed mutations. It turns out to be around 2.7 million years. This is
    consistent with estimates based upon the molecular clocks when CMAH is
    compared with ape CMAH.

    The implications are that here we have a part of our genetic record which is
    demonstrably older than the advent of anatomically modern man and indicates
    that humanity as a population is much older than most Christians prefer to
    believe. If we were all descended from a single pair within the past
    200,000 years, there should not be the variability seen in the CMAH gene.
    Interestingly, they date the chimp/human split at 5.3 million years about
    the time I have advocated on purely geologic considerations. The original
    abstract says (the article will be published in Proc. Natl Acad. Sci Sept 2,

    Published online before print August 21, 2002
    Proc. Natl. Acad. Sci. USA, 10.1073/pnas.182257399

    Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to
    brain expansion during human evolution

    Hsun-Hua Chou, Toshiyuki Hayakawa , Sandra Diaz, Matthias Krings, Etty
    Indriati, Meave Leakey, Svante Paabo , Yoko Satta , Naoyuki Takahata , and
    Ajit Varki

    Humans are genetically deficient in the common mammalian sialic acid
    N-glycolylneuraminic acid (Neu5Gc) because of an Alu-mediated inactivating
    mutation of the gene encoding the enzyme CMP-N-acetylneuraminic acid
    (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last
    common ancestor with bonobos and chimpanzees, and before the origin of
    present-day humans. Here, we take multiple approaches to estimate the timing
    of this mutation in relationship to human evolutionary history. First, we
    have developed a method to extract and identify sialic acids from bones and
    bony fossils. Two Neandertal fossils studied had clearly detectable Neu5Ac
    but no Neu5Gc, indicating that the CMAH mutation predated the common
    ancestor of humans and Neandertals, 0.5-0.6 million years ago (mya). Second,
    we date the insertion event of the inactivating human-specific sahAluY
    element that replaced the ancestral AluSq element found adjacent to exon 6
    of the CMAH gene in the chimpanzee genome. Assuming Alu source genes based
    on a phylogenetic tree of human-specific Alu elements, we estimate the
    sahAluY insertion time at 2.7 mya. Third, we apply molecular clock analysis
    to chimpanzee and other great ape CMAH genes and the corresponding human
    pseudogene to estimate an inactivation time of 2.8 mya. Taken together,
    these studies indicate that the CMAH gene was inactivated shortly before the
    time when brain expansion began in humankind's ancestry, 2.1-2.2 mya. In
    this regard, it is of interest that although Neu5Gc is the major sialic acid
    in most organs of the chimpanzee, its expression is selectively
    down-regulated in the brain, for as yet unknown reasons."


    see http://www.glenn.morton.btinternet.co.uk/dmd.htm
    for lots of creation/evolution information
    personal stories of struggle

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