"The rhesus macaque genome helps illuminate what makes humans different from other apes," said Richard A. Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Center and the project leader of the Rhesus Macaque Genome Sequencing and Analysis Consortium. "It allows us to learn what has been added or deleted in primate evolution from the rhesus macaque to the chimpanzee to the human."

The Rhesus Macaque Genome Sequencing and Analysis Consortium, an international team of more than 170 scientists from 35 institutions, describes their results in a special issue of Science devoted to the macaque genome. The issue consists of a primary Research Article that reports the key findings and four supplementary Reports.

"We want to know what makes us human," Gibbs explained. The human genome, sequenced in 2001 began providing many clues, but researchers knew they would benefit by having other genomes for comparison. In 2005, the chimpanzee (Pan troglodytes) genome allowed scientists to investigate which genes humans shared with this relative, from whom we diverged 6 million years ago.

The macaque is a more ancient relative. This old world monkey diverged from our lineage 25 million years ago. "Because the macaque is further away from us in evolution than the chimp, it provides good contrast when the three genomes are compared," he added. In evolution research, 25 million years is close, and comparing the three genomes can provide new insights not possible before regarding when and where changes occurred during evolution.

Researchers expect that the rhesus macaque genome sequence will enhance research in neuroscience, behavioral biology, reproductive physiology, endocrinology and cardiovascular studies. The macaque is considered the best animal model to study AIDS and is used to study other human infectious disease and for vaccine research.

Because the rhesus macaque is genetically and physiologically similar to humans and abundant, it is frequently used in biomedical research. The monkey has saved countless lives just in the role it has played in determining the Rh factor and polio vaccine, but it has also been key to research into neurological and behavioral disorders.

The new findings described in the Science articles include:

Rhesus macaque genes are about 97.5 percent similar to those of chimps and humans. Chimps and humans have 99 percent of their gene sequences in common.

Researchers identified about 200 genes that show evidence of positive selection during evolution, making them potential candidates for determining the differences among primate species. These genes are involved in hair formation, immune response, membrane proteins and sperm-egg fusion.

Even though macaques are used in human disease research, scientists were surprised to find some instances where the normal form of the macaque protein looks like the diseased human protein. One example occurs in phenylketonuria (PKU) that can lead to brain damage and mental retardation in humans because of a defect in an important enzyme.

Macaque-specific laboratory tests will lead to better understanding of human disease. Researchers previously used human genome data for DNA testing, but macaque-specific DNA chips are being developed that are much more sensitive and accurate.

The DNA for the genome sequencing was contributed by a female rhesus macaque at the Southwest Foundation for Biomedical Research in San Antonio, Texas. The sequencing was performed at the Baylor College of Medicine Human Genome Sequencing Center in Houston, Texas, the Genome Sequencing Center at Washington University in St. Louis, Mo. and the J. Craig Venter Institute in Rockville, Md.

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