Articles > Human-Chimp Differences Uncovered With Analysis Of Rhesus Monkey Genome

Human-Chimp Differences Uncovered With Analysis Of Rhesus Monkey Genome

April 13, 2007 —  An international consortium
of researchers has published the genome sequence of the rhesus macaque
monkey and aligned it with the chimpanzee and human genomes. Published
April 13 in a special section of the journal Science, the analysis
reveals that the three primate species share about 93 percent of their
DNA, yet have some significant differences among their genes.

In its paper, the Rhesus Macaque Genome Sequence and Analysis
Consortium, supported in part by the National Human Genome Research
Institute (NHGRI), one of the National Institutes of Health (NIH),
compared the genome sequences of rhesus macaque (Macaca mulatta) with
that of human (Homo sapiens) and chimp (Pan troglodytes), the primate
most closely related to humans. Four companion papers that relied on
the rhesus sequence also appear in the same issue.

The rhesus genome is the second non-human primate, after the chimp,
to have its genome sequenced and is the first of Old World monkeys to
have its DNA deciphered.

"The sequencing of the rhesus macaque genome, combined with the
availability of the chimp and human genomes, provides researchers with
another powerful tool to advance our understanding of human biology in
health and disease," said NHGRI Director Francis S. Collins, M.D.,
Ph.D. "As we build upon the foundation laid by the Human Genome
Project, it has become clear that comparing our genome with the genomes
of other organisms is crucial to identifying what makes the human
genome unique."

The rhesus, because of its response to the simian immunodeficiency
virus (SIV), is widely recognized as the best animal model for human
immunodeficiency virus (HIV) infection. The rhesus genome sequence will
also serve to enhance essential research in neuroscience, behavioral
biology, reproductive physiology, endocrinology and cardiovascular
studies. In addition, the rhesus serves as a valuable model for
studying other human infectious diseases and for vaccine research.

The sequencing of the rhesus genome was conducted at the Baylor
College of Medicine Human Genome Sequencing Center in Houston, the
Genome Sequencing Center at Washington University School of Medicine in
St. Louis and the J. Craig Venter Institute in Rockville, Md., which
are part of the NHGRI-supported Large-Scale Sequencing Research
Network. The DNA used in the sequencing was obtained from a female
rhesus macaque at the Southwest National Primate Research Center (NPRC)
in San Antonio, which is supported by the National Center for Research
Resources, part of NIH.

Independent assemblies of the rhesus genome data were carried out at
each of the three sequencing centers using different and complementary
approaches and then combined into a single "melded assembly." In their
analysis, scientists from 35 institutions compared this melded assembly
to the reference sequence of the human genome, a newer unpublished
draft sequence of the chimp genome, the sequence of more than a dozen
other more distant species already in the public databases, the human
HapMap, and the Human Gene Mutation Database that lists known human
mutations that lead to genetic disease.

"This study of the rhesus genome is invaluable because it gives
researchers a perspective to observe what has been added or deleted in
each primate genome during evolution of rhesus, chimp, and the human
from their common ancestors ," said Richard Gibbs, Ph.D., director of
Baylor College of Medicine’s Human Genome Sequencing Center in Houston
and the project leader.

One of the most useful features of the rhesus genome is that it is
less closely related to the human genome than to the chimp genome. This
means that important features that have been conserved in primates over
time can be more easily seen by comparing rhesus to human, than chimp
to human.

By adding the rhesus genome to the primate comparison, researchers
identified nearly 200 genes likely to be key players in determining
differences among primate species. These include genes involved in hair
formation, immune response, membrane proteins and sperm-egg fusion.
Many of these genes are located in areas of the primate genome that
have been subject to duplication, indicating that having an extra copy
of a gene may enable it to evolve more rapidly and that small
duplications are a key feature of primate evolution.

The analysis also revealed a few instances in which whole families
of genes were radically different in the rhesus, containing more copies
of certain genes than in the chimp or human. These gene families
include important immune related genes, as well as genes with functions
not yet fully known.

In addition to comparing the rhesus with the chimp and human
genomes, the group also studied genetic variation in macaque
populations, and developed a set of ‘single nucleotide polymorphisms’
or SNPs (single base DNA differences) that can be used for future
analysis of inheritance of biomedically important traits in rhesus. The
rhesus genomic DNA samples used for these studies were contributed by
the California NPRC, Oregon NPRC, Southwest NPRC and Yerkes NPRC. This
advance in macaque genetics will enhance the use of macaques for the
study of genetic diseases of man.

The rhesus study is part of an ongoing program to analyze primate
genomes. Other primate genomes underway include the marmoset, gibbon
and gorilla. Researchers at the Baylor Center and the Washington
University Genome Center completed the raw sequence for the orangutan
and marmoset genomes early this year. Researchers plan to analyze the
orangutan and marmoset genomes and compare them with the other primates
over the summer.

Source : NIH/National Human Genome Research Institute.


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