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Human or Chimp? 50 Genes Are the Key

October 20, 1998

Human or Chimp? 50 Genes Are the Key

Theologians may ponder the difference between God and the
creature made in His image, but biologists have always asked a
humbler question: How do humans differ from other animals?
A proposal now under active discussion promises to provide
an answer of possibly disconcerting precision.

The idea is to identify the genes that are special to humans by
sequencing the genome, or full DNA, of the chimpanzee and
comparing it with the human genome.

Because chimpanzees are so closely related to humans, those
genes that work differently in people than in chimpanzees
could be all that is needed to convert a default-mode great ape
into a human.

The number of such genes may be only a few hundred, out of
the 100,000 genes that humans and chimps are thought to
possess, with just 50 genes accounting for the cognitive differences,
according to scientists at GenoPlex, a company in Denver that is
exploring chimp genes for medical reasons. 

Others, while welcoming pursuit of the new knowledge, foresee
certain hazards that might accompany it, like the temptation to
engineer more human humans through enhanced versions of
the specially human genes, as well as the ethical problems
inherent in trying to test the role of these genes by inserting them
into chimpanzees.

Most human genes have an ancestry that goes back to the earliest
animals and are shared in common with other species. Creatures
as distant from humans as the fruit fly or roundworm have genes
whose DNA sequence is recognizably similar to their human
counterparts, as if they were variant spellings of the same

The Federal human genome project, which aims to decode the three
billion units of human DNA by 2003, will lay the basis for
understanding the human genetic programming as a whole but
is not intended to ferret out the genes unique to humans.

The idea of doing this by means of the chimp genome was first
proposed a year ago by two biologists who study evolution at
the DNA level, Edwin McConkey of the University of Colorado
at Boulder and Morris Goodman of Wayne State University in
Detroit. Their proposal was further explored at a meeting this month
at the Field Museum of Natural History in Chicago.

So far the leading supporter of chimp genome research in the
United States has been GenoPlex, a company founded by two
University of Colorado biologists, James M. Sikela and Thomas
E. Johnson. The company has already identified a gene that
may contribute toward chimpanzees' greater resistance to AIDS.

DNA, the chemical tape that embodies the genetic programming,
changes very slowly. Chimpanzees and humans are thought to
have taken different evolutionary paths only five million years
ago, a mere eye blink in evolutionary time. Because the two
species shared an ancestor so recently, their DNA is on average 98.4
percent identical. 

It is a serious puzzle for biologists to explain how two such
similar genetic programs generate such different animals. Dr. David
L. Nelson, a biologist at the Baylor College of Medicine, said that
some of the anatomical differences between chimps and humans
might arise from very small changes in the genes that regulate
fetal development.

The human brain is about twice the size of the chimpanzee brain,
but a genetic program that allowed time for the brain cells in the
developing fetus to go through just one more doubling would
account for the difference, Nelson said. The human face is tucked
underneath the brain case instead of projecting beyond it as in the
chimp, but this could be arranged just by arresting the forward
movement of the face during fetal development.

Still, there are many other human-chimp differences that have to
be generated by the almost identical genetic programs. Dr. Nelson
thinks some of the differences might be explained by a phenomenon
that lies beyond the mere sequence of DNA.

With a colleague, Elizabeth Nickerson, he has been studying a
curious rearrangement in chimpanzee chromosomes, the bundles
in which DNA molecules are packaged. Compared with humans,
chimps have five chromosomes in which a central segment has been
flipped. Genes on the flipped portion of the chromosomes would
find themselves in a different environment and might be more or
less active than before, Dr. Nelson said. Even a small difference
in the activity of a high-level regulatory gene could produce significant
effects in the developing animal.

The genes that make humans more than just another great ape are
unlikely to be totally novel genes, experts say, but rather ones that
acquired a new role compared with their counterparts in the chimps.
These genes would have been under strong evolutionary pressure, a
force that can often be detected through a quirk in the genetic code, the
system through which sets of three DNA units, or nucleotides, specify
the 20 amino acid building blocks of proteins. The code is somewhat
ambiguous in that in some cases one nucleotide can change or mutate
to another without changing the specified amino acid. These changes
are silent, meaning that they make no difference to the organism
and are almost neutral in terms of its survival prospects.

Nucleotide mutations that do change the specified amino acid are
usually harmful, and thus are less common than the silent mutations.
On the rare occasions when these consequential mutations are
beneficial, they are quickly favored by natural selection and
outnumber the silent mutations. 

Sikela hopes to identify the few hundred genes that are special to
humans by pinpointing genes that have been under strong selective
pressure. His plan is to compare the DNA sequence of human
genes and their chimp counterparts, and look for genes in which
consequential changes outweigh the silent ones.

Many changes that seem distinctively human, like larger brain
size, are in fact evolutionary trends that began far earlier in the
primate line.  Goodman thinks it will be necessary to sequence
the genomes of a series of primate species in order to clarify
these trends. To explore each of the major branch points leading to
humans over the last 60 million years, he would like someone to
sequence lemurs, bush babies, pottos, tarsiers, capuchin monkeys,
rhesus monkeys, gibbons, orangutans, gorillas, chimps and bonobos.

Dr. Francis Collins, director of the human genome project at the
National Institutes of Health, said that having the chimp genome in hand
would be extremely useful and that he would consider financing pilot
projects to sequence the chimp genome, not from scratch but through
its differences with human DNA. 

Discovery of the genes that are special to humans might not be
without hazard. 

"The more we learn about the genes that are crucial for our
uniquely human characteristics, the greater the temptation to
produce humans that have optimal combinations of these genes,
or even enhanced genes," McConkey said.

Another problem is that biologists might wish to test the supposed
role of the uniquely human genes by inserting them into chimpanzees.
"I don't know whether society will ever be comfortable with such a
drastic thing as adding a human gene to an ape," McConkey said.