Genes of Humans and Chimps 96 Percent the Same

CAMBRIDGE, Massachusetts, September 2, 2005 (ENS) - The first comprehensive comparison of the genetic blueprints of humans and chimpanzees shows that the DNA sequence of the two species is 96 percent identical, an international research consortium reported Thursday. The comparison is based on the first sequencing and assembly of the chimpanzee genome just completed by researchers from the United States, Israel, Italy, Germany and Spain.

The scientists say their findings provide "unambiguous confirmation of the common and recent evolutionary origin of human and chimpanzees, as first predicted by Charles Darwin in 1871."

Led by scientists from the Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, and the Washington University School of Medicine in Saint Louis, Missouri, the Chimpanzee Sequencing and Analysis Consortium reported its findings in the September 1 issue of the journal "Nature."

"We now have a nearly complete catalog of the genetic changes that occurred during the evolution of the modern human and chimpanzee species from our common ancestor," said the study's lead author, Tarjei Mikkelsen of the Broad Institute.


Bioinformaticist Tarjei Mikkelsen is a faculty member at the Broad Institute. (Photo courtesy Broad Institute)
"By cross-referencing this catalog against clinical observations and other biological data," Mikkelsen said, "we can begin to identify the specific changes that underlie the unique traits of the human species."

The 67 researchers who took part in the Chimpanzee Sequencing and Analysis Consortium share authorship of the "Nature" paper. The sequencing and assembly of the chimpanzee genome was done at the Broad Institute and at the Washington University School of Medicine in Saint Louis, Missouri.

The work of the Chimpanzee Sequencing and Analysis Consortium is funded in part by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health.

The research was conducted on tissue from a chimpanzee named Clint from the Yerkes National Primate Research Center at Emory University. He died in January at the age of 24.

The chimpanzee is the first primate and the fourth mammalian genome to be sequenced.

The fact that these data, and all future data from the Consortium, are being placed in the public domain means that scientists worldwide can contribute to this work.

The initial complete sequence of the chimpanzee genome and comparison to the human genome is an important milestone in what will be several years of intensive work at understanding human evolutionary history and applying these data to biomedical research, the scientists said.


The DNA of this chimp, Clint, was used to sequence the chimpanzee genome. (Photo courtesy Washington University School of Medicine)
"The evolutionary comparison of the human and chimpanzee genomes has major implications for biomedicine," said Eric Lander, director of the Broad Institute. "It provides a crucial baseline for human population genetic analysis. By identifying recent genetic changes and regions with unusually high or low variation, it can point us to genes that vary as a response to infectious agents and environmental pressures."

The Consortium found that the chimpanzee and human genomes are "strikingly 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 chimpanzees still share 96 percent sequence identity.

At the protein level, 29 percent of genes code for the same amino sequences in chimpanzees and humans. In fact, the typical human protein has accumulated just one unique change since chimpanzees and humans diverged from a common ancestor about six million years ago.

About 35 million DNA base pairs differ between the shared portions of the two genomes. In addition, there are another five million sites that differ because of an insertion or deletion in one of the lineages, along with a much smaller number of chromosomal rearrangements.

As many as three million of the differences are found in crucial protein-coding genes or other functional areas of the genome. "Somewhere in these relatively few differences lies the biological basis for the unique characteristics of the human species, including human-specific diseases such as Alzheimer's disease, certain cancers, and HIV/AIDS," the researchers say.

"We're excited about being able to compare our own genetic blueprint with that of our closest living relative," says Richard K. Wilson, Ph.D., director of the Genome Sequencing Center (GSC) at Washington University School of Medicine in St. Louis.


Richard K. Wilson, Ph.D. is director of the Genome Sequencing Center (GSC) at Washington University School of Medicine in St. Louis. (Photo courtesy
"Over the next few years, such a comparison will allow us to learn more about how our own genome has evolved and gain a better understanding as to why we get cancers and other diseases that chimpanzees very rarely suffer," said Wilson, who with other scientists at the GSC sequenced half the chimpanzee genome and coauthored the analysis.

The researchers explain that humans and chimpanzees 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, the researchers believe they may have also made primates more adaptable to rapid environmental changes and enabled them to achieve unique evolutionary adaptations.

The scientists also found 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 ions.

They say the rapid evolution of these genes may have contributed to the special characteristics of primates.

The research was co-led by Dr. Robert Waterston of the University of Washington in Seattle, chair of the university's Department of Genome Sciences at the University of Washington School of Medicine. "For the human genome," he said, "we are using comparative sequence analysis, first with mouse and currently with chimpanzee, to explore the ways comparative analysis can illuminate the function of the human genome."

Waterston's University of Washington colleague Dr. Evan Eichler, a Howard Hughes Medical Institute investigator, studied the chimp genome, looking for large-scale segmental duplications that consist of as many as 20,000 base pairs.

He found that most of the change to the overall genome landscape between chimps and humans can be attributed to large segmental duplications.

Such large-scale genetic events have altered more total base pairs - about 2.7 percent of the genome - than differences from single base-pair changes, which account for about 1.2 percent of the genome.

"For all the talk of the 1.2 percent single base-pair difference and the importance of those, there's even more difference between the species due to duplication events," said Eichler. "Now we need to learn the role of those duplication events in species evolution and disease."