Analysis of Rhesus Monkey Genome Uncovers Genetic
Differences With Humans, Chimps
DNA Comparison Provides New Clues to Primate Biology
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 the 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, and Washington University
has deposited the assemblies at the Genome Sequencing Center [genome.wustl.edu].
Researchers plan to analyze the orangutan and marmoset genomes
and compare them with the other primates over the summer.
The chimp, orangutan and human genome sequences, along with those
of a wide range of other organisms such as mouse, rat, dog, cow,
honey bee, roundworm and yeast, can be accessed through the following
public genome browsers: GenBank (www.ncbi.nih.gov/Genbank) at NIH's
National Center for Biotechnology Information (NCBI); the UCSC
Genome Browser (www.genome.ucsc.edu) at the University of California
at Santa Cruz; the Ensembl Genome Browser (www.ensembl.org) at
the Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics
Institute; the DNA Data Bank of Japan (www.ddbj.nig.ac.jp); and
EMBL-Bank, (www.ebi.ac.uk/embl/index.html) at the European Molecular
Biology Laboratory's Nucleotide Sequence Database.
NHGRI is one of 27 institutes and centers at the NIH, an agency
of the Department of Health and Human Services. The NHGRI Division
of Extramural Research supports grants for research and for training
and career development at sites nationwide. Additional information
about NHGRI can be found at its Web site, www.genome.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
|