|New Genome Comparison Finds Chimps, Humans Very Similar at
the DNA Level
The first comprehensive comparison of the genetic blueprints of humans and
chimpanzees shows that our closest living relatives share perfect identity with
96 percent of our DNA sequence, an international research consortium reported
In a paper published in the Sept. 1 issue of the journal Nature, the
Chimpanzee Sequencing and Analysis Consortium, which is supported in part by
the National Human Genome Research Institute (NHGRI), one of the National Institutes
of Health (NIH), describes its landmark analysis comparing the genome of the
chimp (Pan troglodytes) with that of human (Homo sapiens).
“The sequencing of the chimp genome is a historic achievement that is destined
to lead to many more exciting discoveries with implications for human health,” said
NHGRI Director Francis S. Collins, M.D., Ph.D. “As we build upon the foundation
laid by the Human Genome Project, it’s become clear that comparing the human
genome with the genomes of other organisms is an enormously powerful tool for
understanding our own biology.”
The chimp sequence draft represents the first non-human primate genome and the
fourth mammalian genome described in a major scientific publication. A draft
of the human genome sequence was published in February 2001, a draft of the mouse
genome sequence was published in December 2002 and a draft of the rat sequence
was published in March 2004. The essentially complete human sequence was published
in October 2004.
“As our closest living evolutionary relatives, chimpanzees are especially suited
to teach us about ourselves,” said the study’s senior author, Robert Waterston,
M.D., Ph.D., chair of the Department of Genome Sciences of the University of
Washington School of Medicine in Seattle. “We still do not have in our hands
the answer to a most fundamental question: What makes us human? But this genomic
comparison dramatically narrows the search for the key biological differences
between the species.”
The 67 researchers who took part in the Chimp Sequencing and Analysis Consortium
share authorship of the Nature paper. Most of the work of sequencing
and assembling the chimp genome was done at the Broad Institute of the Massachusetts
Institute of Technology and Harvard University, Cambridge, Mass., and the Washington
University School of Medicine in Saint Louis. In addition to those centers, the
consortium included researchers from institutions elsewhere in the United States,
as well as Israel, Italy, Germany and Spain.
The DNA used to sequence the chimp genome came from the blood of a male chimpanzee
named Clint at theYerkes National Primate Research Center in Atlanta. Clint died
last year from heart failure at the relatively young age of 24, but two cell
lines from the primate have been preserved at the Coriell Institute for Medical
Research in Camden, N.J.
The consortium found that the chimp and human genomes are very similar and encode
very similar proteins. The DNA sequence that can be directly compared between
the two genomes is almost 99 percent identical. When DNA insertions and deletions
are taken into account, humans and chimps still share 96 percent of their sequence.
At the protein level, 29 percent of genes code for the same amino sequences in
chimps and humans. In fact, the typical human protein has accumulated just one
unique change since chimps and humans diverged from a common ancestor about 6
million years ago.
To put this into perspective, the number of genetic differences between humans
and chimps is approximately 60 times less than that seen between human and mouse
and about 10 times less than between the mouse and rat. On the other hand, the
number of genetic differences between a human and a chimp is about 10 times more
than between any two humans.
The researchers discovered that a few classes of genes are changing unusually
quickly in both humans and chimpanzees compared with other mammals. These classes
include genes involved in perception of sound, transmission of nerve signals,
production of sperm and cellular transport of electrically charged molecules
called ions. Researchers suspect the rapid evolution of these genes may have
contributed to the special characteristics of primates, but further studies are
needed to explore the possibilities.
The genomic analyses also showed that humans and chimps appear to have accumulated
more potentially deleterious mutations in their genomes over the course of evolution
than have mice, rats and other rodents. While such mutations can cause diseases
that may erode a species’ overall fitness, they may have also made primates more
adaptable to rapid environmental changes and enabled them to achieve unique evolutionary
adaptations, researchers said.
Despite the many similarities found between human and chimp genomes, the researchers
emphasized that important differences exist between the two species. About 35
million DNA base pairs differ between the shared portions of the two genomes,
each of which, like most mammalian genomes, contains about 3 billion base pairs.
In addition, there are another 5 million sites that differ because of an insertion
or deletion in one of the lineages, along with a much smaller number of chromosomal
rearrangements. Most of these differences lie in what is believed to be DNA of
little or no function. However, as many as 3 million of the differences may lie
in crucial protein-coding genes or other functional areas of the genome.
“As the sequences of other mammals and primates emerge in the next couple of
years, we will be able to determine what DNA sequence changes are specific to
the human lineage. The genetic changes that distinguish humans from chimps will
likely be a very small fraction of this set,” said the study’s lead author, Tarjei
S. Mikkelsen of the Broad Institute of MIT and Harvard. Among the genetic changes
that researchers will be looking for are those that may be related to the human-specific
features of walking upright on two feet, a greatly enlarged brain and complex
Although the statistical signals are relatively weak, a few classes of genes
appear to be evolving more rapidly in humans than in chimps. The single strongest
outlier involves genes that code for transcription factors, which are molecules
that regulate the activity of other genes and that play key roles in embryonic
A small number of other genes have undergone even more dramatic changes. More
than 50 genes present in the human genome are missing or partially deleted from
the chimp genome. The corresponding number of gene deletions in the human genome
is not yet precisely known. For genes with known functions, potential implications
of these changes can already be discerned.
For example, the researchers found that three key genes involved in inflammation
appear to be deleted in the chimp genome, possibly explaining some of the known
differences between chimps and humans in respect to immune and inflammatory response.
On the other hand, humans appear to have lost the function of the caspase-12 gene,
which produces an enzyme that may help protect other animals against Alzheimer’s
“This represents just the tip of the iceberg when it comes to exploring the
genomic roots of our biological differences,” said one of the study’s co-authors
LaDeana W. Hillier of the Genome Sequencing Center at Washington University School
of Medicine. “As more is learned about other functional elements of the genome,
we anticipate that other important differences outside of the protein-coding
genes will emerge.”
Armed with the chimp sequence, researchers also scanned the entire human genome
for deviations from normal mutation patterns. Such deviations may reveal regions
of “selective sweeps,” which occur when a mutation arises in a population and
is so advantageous that it spreads throughout the population within a few hundred
generations and eventually becomes “normal.”
The researchers found six regions in the human genome that have strong signatures
of selective sweeps over the past 250,000 years. One region contains more than
50 genes, while another contains no known genes and lies in an area that scientists
refer to as a “gene desert.” Intriguingly, this gene desert may contain elements
regulating the expression of a nearby protocadherin gene, which has been implicated
in patterning of the nervous system. A seventh region with moderately strong
signals contains the FOXP2 and CFTR genes. FOXP2 has
been implicated in the acquisition of speech in humans. CFTR, which
codes for a protein involved in ion transport and, if mutated, can cause the
fatal disease cystic fibrosis, is thought to be the target of positive selection
in European populations.
The chimp and human genome sequences, along with those of a wide range of other
organisms such as mouse, 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 (http://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 investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.