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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.




Copyright 1999 The New York Times Company


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