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News

Newly completed chimp genome helps scientists learn more about human DNA

Washington University In St Louis : 03 August, 2006  (Technical Article)
Sequencing the human genome was not the end of the Human Genome Project, says Richard Wilson.Comparing the human genome to the chimpanzee genome has allowed scientists to identify changes in the human genetic code that were so advantageous that they rapidly became the norm throughout humanity.
Sequencing the human genome was not the end of the Human Genome Project, says Richard Wilson.Comparing the human genome to the chimpanzee genome has allowed scientists to identify changes in the human genetic code that were so advantageous that they rapidly became the norm throughout humanity.

The areas of human DNA where these changes occurred are currently the subject of follow-up investigations to identify the potentially vital contributions they now make to human health and development.

Scientists detail their initial analysis of the chimp genome, conducted largely in the context of human-chimp comparisons, in Nature. According to the researchers, the chimp genome's remarkable closeness to the human genome will make it a powerful tool for comparative genetics, which uses interspecies comparisons to identify areas of interest in the vast fields of data contained in DNA.

'We're excited about being able to compare our own genetic blueprint with that of our closest living relative,' says Richard K. Wilson, Ph.D., director of the Genome Sequencing Center at Washington University School of Medicine in St. Louis. 'Over the next few years, such a comparison will allow us to learn more about how our own genome has evolved and gain a better understanding as to why we get cancers and other diseases that chimpanzees very rarely suffer.'

Clint's DNA was used to sequence the chimp genome.
Wilson and other scientists at the GSC sequenced half the chimpanzee genome and coauthored the analysis. It is the first primate and the fourth mammalian genome to be sequenced. Much of the additional sequencing was produced by scientists at the Broad Institute of the Massachusetts Institute of Technology and Harvard University. Their work was supported by grants from the National Human Genome Research Institute.

Both the chimpanzee and the human genome contain approximately 20,000-25,000 protein-coding genes in 3 billion base pairs of DNA. The current sequences of the human and chimp genomes are directly comparable over approximately 96 percent of their lengths, and these regions are 99 percent identical.

The initial analysis provides the first detailed look at the genetic changes that prompted the chimp-human species divergence and an intriguing glimpse of how the evolution of both species has continued since that divergence. As other primate and mammalian genomes become available in the next few years, comparative genetics will help scientists identify many features in our DNA that are responsible for the unique characteristics that make us human, including advanced cognitive and linguistic abilities.

Because the chimp and human genomes are so similar, researchers' efforts to uncover genetic roots of the two species' differences will focus not only on the identification of altered or unique genes but also on how largely similar genes are used differently. Changes in how frequently a protein is made from a particular gene or in the way a gene's protein-building instructions are spliced together can dramatically change the gene's effects.

Scientists suspect such changes in gene usage may be a primary contributor to the differences in chimpanzee and human brains. An early comparison suggests the added complexity and larger size of the human brain versus the chimp brain owes much less to the development of new human genes for brain proteins than it does to changes in the way existing genes are used as the human brain develops.

Since their divergence, areas of rapid genetic change in both species include reproduction, the sense of smell and immunity, all of which are also areas of rapid change for other mammals. Scientists found several genes for olfactory receptors in chimpanzees had become pseudogenes in humans. Such genes are still recognizable for the function they once fulfilled but have been disabled through slight changes in their coding.

In both humans and chimps, the tips of the chromosomes typically accumulate mutations much more quickly than the interiors of the chromosomes. Areas of chimp and human DNA that are evolving faster than in other mammals include genes linked to ion transport, a common signaling process active throughout the body; transmissions between nerve cells; and perception of sound.

Of the protein-making genes in the two genomes, one-third have identical sequences. The number of differences between the chimp genome and the human genome is 10 times that which occurs between any two humans, but it's also 10 times less than the differences between the mouse and rat genomes.

The chimpanzee-human genome comparison revealed approximately 35 million instances of a change of a single character in the DNA code, and 5 million sites where larger changes were present. Partial or complete deletions had removed or disabled more than 50 genes, and other types of mutations had disabled a number of additional genes.

Many of the differences were due to disruptive insertions in the genetic code. Chimpanzee DNA, for example, shows several instances of having incorporated segments from viruses that are often duplicated and reinserted at various points in the genome. In humans, the Alu element, a non-viral segment of DNA that tends to get copied and inserted around the genome, was a significant source of these changes.

As researchers compare and contrast chimp and human data with other primate and mammalian genomes scheduled for completion in the next few years, they should be able to disregard such areas of change and zero in on the small group of genetic alterations responsible for unique aspects of human nature.
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