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Genetic Mutations Accumulating Rapidly, Scientists Say



        January 28, 1999

        Genetic Mutations Accumulating Rapidly, Scientists Say

        By NICHOLAS WADE

            Biologists analyzing human genetic data in the
            DNA data banks have given fresh meaning to
        the saying that no one is perfect. Harmful mutations
        have accumulated so fast in the human genome,
        according to a new study, that the immediate
        question is why the human species has not become
        extinct. 

        Although human populations are evidently doing
        fine, common minor afflictions like weakened
        eyesight, headaches and stomach upsets could reflect
        this inherited baggage of adverse mutations. And
        some biologists fear that as the bite of natural
        selection is relaxed by medical advances, the
        mutational baggage could become more significant in
        the centuries ahead. 

        The effective mutation rate in the human genome is
        estimated in the new study as being at least 4.2
        mutations per generation, of which at least 1.6
        mutations are harmful. This is a high number
        considering that a harmful mutation can be
        eliminated sooner or later only by the "genetic
        death" -- death without progeny -- of its carrier. 

        The study also found that humans have retained a
        much larger proportion of adverse mutations in their
        genome than have other animals, like mice and rats.
        The authors of the study, which appears in
        Thursday's issue of Nature, are Adam Eyre-Walker
        of the University of Sussex in England and Peter D.
        Keightley of the University of Edinburgh. 

        The high retention of adverse mutations probably
        reflects the fact that human populations have been
        extremely small throughout their evolutionary
        history. In small populations it is easier for a
        mutation to become fixed. 

        "Our genome appears to be degenerating in one
        sense," said Eyre-Walker. But he noted that the
        seriousness of the adverse mutations was unknown
        and in any case had been outweighed "by some key
        adaptations that have made us very successful,"
        presumably intelligence. 

        The new finding is principally of interest to those
        engaged in human evolutionary history and has little
        immediate bearing on the genetic health of
        present-day populations, because the adverse
        mutations that were found are all probably small in
        effect, even if large in number. 

        One theoretical implication of interest to
        evolutionists is that the high mutation rate confirms a
        long-standing speculation about the purpose of sex.
        Biologists have often wondered why a species
        would go to the bother of sexual reproduction when
        division without sex, the way the amoebas do it,
        would seem to be more efficient. A favorite answer
        is that sexual reproduction, in which the genomes are
        shuffled between generations, is an relatively
        efficient way of shedding adverse mutations. 

        The high rate of adverse mutation found in the new
        study confirms that some efficient mechanism --
        presumably sex -- is required to remove bad
        mutations from the genome. "To flush out these
        deleterious mutations we need sex," Eyre-Walker
        said. "If we were asexual we would probably be
        dead." 

        Dr. James F. Crow, a population geneticist at the
        University of Wisconsin in Madison, confirmed
        Eyre-Walker's interpretation. "The existence of a
        high deleterious mutation rate strengthens the
        argument that a major advantage of sex is that it is an
        efficient way to eliminate harmful mutations," he
        writes in a commentary on the paper. The cleansing
        action of sex arises because bad mutations are
        brought together and eliminated. 

        Sex has not been completely efficient, however, and
        many adverse mutations still remain in the human
        genome. Crow is concerned that the mutational
        baggage may increase in the future because of higher
        living standards that allow most infants to reach
        reproductive age. "Can we keep this up forever?" he
        wondered. "I don't know." 

        Using DNA sequences now on deposit in DNA data
        banks, the study compared humans and chimpanzees.
        Each DNA difference was declared to be a human
        mutation if in a third species, usually a gorilla, the
        DNA was the same as the chimp's. 

        Some mutations are inconsequential because they do
        not change the sequence of amino acids in a protein
        and therefore have no effect on the organism's
        survival. By measuring the numbers of
        inconsequential and of effective mutations, the
        researchers were able to compute the rate at which
        mutations entered the genome over the last 6 million
        years. 




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