Chimp chromosome creates puzzles
First sequence is unexpectedly different from human equivalent.
27 May 2004
LAURA NELSON
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| Thousands of chimp genes could significantly differ from those in humans. |
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What is the difference between a chimp and a human? There could be a lot
more to the answer than scientists thought, according to the first accurate
DNA sequence of a chimp chromosome.
We already knew that around 98.5% of the base pairs that make up our DNA
are the same as those in chimps. So the old idea was that all the things
that differentiate us from apes, such as highly developed cognitive functions,
walking upright and the use of complex language, should come from the other
1.5%.
Scientists had hoped this would mean the key genetic changes that enabled
such traits to evolve would be easy to find. But the latest evidence suggests
that the journey from ape to human was much more complex.
Todd Taylor at the Riken Genomic Sciences Center in Yokohama, Japan, and
his colleagues have read the DNA sequence of chimpanzee chromosome 22, and
compared it to its human counterpart, chromosome 21. Although a draft sequence
of the chimp genome has been available since August 2003, this is the first
sequence of a whole chimp chromosome that is accurate enough for researchers
to be sure that any differences between the two species are real, and not
just data errors.
Not so human
The sequences of chimp chromosome 22 and human chromosome 21 are roughly
equivalent. Out of the bits that line up, 1.44% of the individual base pairs
were different, settling a debate based on previous, less accurate studies.
However, the researchers were in for a surprise. Because chimps and humans
appear broadly similar, some have assumed that most of the differences would
occur in the large regions of DNA that do not appear to have any obvious
function. But that was not the case. The researchers report in Nature1
that many of the differences were within genes, the regions of DNA that code
for proteins. 83% of the 231 genes compared had differences that affected
the amino acid sequence of the protein they encoded. And 20% showed "significant
structural changes".
In addition, there were nearly 68,000 regions that were either extra or
missing between the two sequences, accounting for around 5% of the chromosome.
"We already knew that at the DNA level we are similar to chimpanzees," says
Taylor. "But we have seen a much higher percentage of change than people
speculated."
The researchers also carried out some experiments to look at when and
how strongly the genes are switched on. 20% of the genes showed significant
differences in their pattern of activity.
Chromosome 22 makes up only 1% of the genome, so in total there could
be thousands of genes that significantly differ between humans and chimps,
says Jean Weissenbach from France's National Sequencing Centre in Evry. This
could make it much harder than scientists had hoped to find the key changes
that made us human.
Nonetheless, Taylor and his team plan to use their chimp sequence to home
in on important differences between the two species. "We have to work out
which proteins have a functional impact," says Taylor. The researchers have
already identified two genes called NCAM2 and GRIK1, the human
versions of which contain large sections that are missing in the chimp. Both
genes are known to be involved in neural function.
Genome feast
The sequence of chromosome 22 has also whetted researchers' appetites
for the full chimp genome sequence, due to be published in Nature
later this year. "The small section of the genome is very valuable," says
Ajit Varki, a molecular biologist at the University of California, San Diego.
"But the whole genome will be a wonderful tool."
Weissenbach is looking even further ahead. He points out that the best
way to narrow down which of the differences between the two genomes are really
key to making us human is to compare the sequences with those of other great
apes. "Do we now need the gorilla genome sequence?" he says.
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