Chimp chromosome creates puzzles
First sequence is unexpectedly different from human equivalent.
27 May 2004
LAURA NELSON

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.


References
Fujiyama, A. et al. Nature, 429, 382, doi:10.1038/nature02564 (2004).

>From Nature
http://www.nature.com/nsu/040524/040524-8.html

Posted by
Robert Karl Stonjek.
---
þ RIMEGate(tm)/RGXPost V1.14 at BBSWORLD * Info{at}bbsworld.com

---
 * RIMEGate(tm)V10.2áÿ* RelayNet(tm) NNTP Gateway * MoonDog BBS
 * RgateImp.MoonDog.BBS at 6/2/04 6:25:27 AM