“Chimp Chromosome Creates Puzzles: First Sequence is Unexpectedly Different from Human Equivalent: Thousands of Chimp Genes Could Significantly Differ from Those in Humans”


Laura Nelson


May 27, 2004; 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 percent 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 percent.


            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 percent 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 Nature [Ref.] that many of the differences were within genes, the regions of DNA that code for proteins. 83 percent of the 231 genes compared had differences that affected the amino acid sequence of the protein they encoded. And 20 percent 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 percent 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 percent of the genes showed significant differences in their pattern of activity.  Chromosome 22 makes up only 1 percent 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 Center in Evry. This could make it much harder than scientists had hoped to find the key changes that made us human.


            Nevertheless, 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 at 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.


Ref.: H. Watanabe, A. Fujiyama, M. Hattori, T. D. Taylor, A. Toyoda, Y. Kuroki, H. Noguchi, A. BenKahla, H. Lehrach, R. Sudbrak, M. Kube, S. Taenzer, P. Galgoczy, M. Platzer, M. Scharfe, G. Nordsiek, H. Blöcker, I. Hellmann, P. Khaitovich, S. Pääbo, R. Reinhardt, H.-J. Zheng, X.-L. Zhang, G.-F. Zhu, B.-F. Wang, G. Fu, S.-X. Ren, G.-P. Zhao, Z. Chen, Y.-S. Lee, J.-E. Cheong, S.-H. Choi, K.-M. Wu, T.-T. Liu, K.-J. Hsiao, S.-F. Tsai, C.-G. Kim, S. OOta, T. Kitano, Y. Kohara, N. Saitou, H.-S. Park, S.-Y. Wang, M.-L. Yaspo5, Y. Sakaki, “DNA Sequence and Comparative Analysis of Chimpanzee Chromosome 22,” Nature, Vol. 429, pp. 382-8 (May 27, 2004).



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