Understanding of primate evolution advanced

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The completed DNA sequence of the rhesus macaque ,an Old World monkey, has advanced understanding of primate evolution and will enhance medical research in neuroscience, behavioral biology, reproductive physiology, endocrinology, heart and blood vessel disease and immunodeficiency, said scientists at the Baylor College of Medicine (BCM) Human Genome Sequencing Center who led the effort.

The generation of the sequence was a collaboration of the BCM group with the Genome Sequencing Center at Washington University in St. Louis, Mo., and the J. Craig Venter Institute in Rockville, Md., in cooperation with the Michael Smith Genome Sciences Center at the British Columbia Cancer Agency in Vancouver.

Independent assemblies of the rhesus genome data were carried out at each of the three sequencing centers and these were later joined into a "melded assembly." The availability of the data was announced at the end of 2005.

The subsequent analysis, published in a special section of today's issue of the journal Science, was performed over a period of nine months and involved scientists from more than 35 Institutions. The total list of authors included more than 170 individuals.

The report compares the genome sequences of the human, chimpanzee and rhesus macaque in order to identify those changes that were important in shaping the biology of the three primate species over the past 25 million years.

The macaque genome differs by approximately seven percent from that of humans, while chimpanzees are just one to two percent different. The added divergence of the macaque makes it ideal for this kind of evolutionary study.

Project leader for the effort was author Dr. Richard Gibbs, director of the BCM Center. The sequence will also enhance the primates' value in understanding various systems of the human body.

"This sequence and its comparison to that of the human and chimpanzee enable us to look back at history at how these species evolved and diverged," said Gibbs. "It points to genes that are important for defining the difference between the species."

The study showed examples of duplicated segments of the genome, expanded gene families and individual genes that had been influenced by natural selection. One gene family was shown to have expanded dramatically in the primate lineage, but much more so in humans than macaques. In contrast, another gene family 'the HLA complex' is much larger in macaques and may play a key role in defining their immune response.

Analysis of chromosomal rearrangements that could not be detected by regular cytogenetic techniques was carried out by Dr. Aleks Milosavljevic and a graduate student, Alan Harris.

"We were surprised to find a high density of significant sub-microscopic rearrangements on the X chromosome," said Milosavljevic, "giving us new evidence of the unusual role of this sex-chromosome in primate evolution."

The data herald a new era where reagents can be tailored specifically for the rhesus macaque.

"In the future, we hope to develop DNA microarrays or gene chips specific to the macaque, which will enable us to pinpoint the level of gene expression in various studies such as those that look at the virulence and pathogenicity of pandemic strains of the influenza virus," said Dr. George Weinstock, co-director of the BCM Center.

"For example, a complete description of all the different macaque immune function components will enable an even more thoughtful use of rhesus macaques in areas such as AIDS research and for vaccine production," the authors wrote.

An important part of the study was a survey of DNA sequence differences between macaque individuals. This established that macaques show a similar overall genetic conservation to humans but that the Indian subpopulation was affected by a recent bottleneck in size. This work will speed future genetic studies of macaques, both in the laboratory and in the wild.

"A comparison of different individuals at the DNA sequence level is key to the understanding of the role of genetic variation in governing individual disease response," said Dr. Kim Worley, a senior HGSC scientist working on the project.

The information will also enable researchers to explore the basic biology of these animals, who live healthily across a broad geographic area. Finally, the researchers noted, the variations in genetic material, rearrangements, duplications, expansions in genes and measurements of the impact of natural selection reveal the rich and heterogeneous genomic changes that have occurred during the evolution of the human, chimpanzee and macaque.

"The analysis of this important primate is another milestone of the achievements of the College and marks its ongoing contributions to basic research", said Dr. Peter G, Traber, president of BCM.

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