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HARVARD GAZETTE ARCHIVES

Chimp genome effort shines light on human evolution

Broad Institute and Washington University lead the decoding effort

By Alvin Powell
Harvard News Office

An international research consortium has unraveled the chimpanzee genetic code, finding that humans and chimps share 96 percent of their genetic blueprint in an advance that has already begun to shed light on what makes humans "human."

'Nature' cover

The research effort, led by scientists at the Broad Institute of MIT and Harvard, the Washington University School of Medicine in St. Louis, and the University of Washington, Seattle, focused on the chimpanzee in hopes that genetic comparisons with humanity's closest relative will lead to answers to both practical questions - such as the causes of human disease - and to more fundamental questions on human biology.

In addition to their obvious physical differences, humans and chimpanzees have different responses to Alzheimer's disease, malaria, and HIV/AIDS, for example.

"We're focusing on the differences as a way to shed light on ourselves," said Eric Lander, Broad Institute director and professor of systems biology at Harvard Medical School, who led the project along with Richard Wilson of the Washington University School of Medicine in St. Louis and Robert Waterston of the University of Washington, Seattle. "This is a case where evolutionary analysis is a direct handmaiden to biomedicine."

Among the 3 billion base pairs in the DNA of both humans and chimpanzees, researchers found differences in 40 million sites. It is in those sites where the differences between the two species lie.

"Just what makes us human? Now, in a sense, we can answer that question," said Tarjei Mikkelsen of the Broad Institute and the research paper's lead author. "We now have a nearly complete catalog of all genetic differences between humans and chimps and there's about 40 million of them. And any human-specific trait that's encoded in our DNA is caused by one or more of those 40 million changes."

The research, published in the Sept. 1 issue of the journal Nature, puts the chimpanzee with humans, mice, and rats as the only mammals whose DNA has been decoded and published in a major scientific journal.

When measured by changes in their genetic codes, humans and chimpanzees are about 10 times more different than are individual humans from each other. By comparison, human and mouse DNA have about 60 times more differences than do human and chimpanzee DNA.

The research was conducted by the Chimpanzee Sequencing and Analysis Consortium, which involved 67 researchers in the United States, Israel, Italy, Germany, and Spain. The sequencing and assembly of the chimpanzee genome was done at the Broad Institute and at the Washington University School of Medicine in St. Louis.

In addition to the Broad Institute, which is a collaboration of Harvard and the Massachusetts Institute of Technology, the effort involved researchers from Harvard Medical School and the Faculty of Arts and Sciences.

The work, funded by the National Institutes of Health's National Human Genome Research Institute, cost between $20 million and $30 million. It was released at a news conference in Washington, D.C., Aug. 31. The DNA used in the project came from a chimp at the Yerkes National Primate Research Center in Atlanta named Clint, who died last year from heart failure.

Reading the code

An organism's genetic code is contained in long, complex molecules called DNA located in the nucleus of every cell. DNA is a ladderlike structure made up of joined pairs of just four kinds of subunits called bases. The sequence of these bases - which vary from human to human and from chimpanzee to human - contain an organism's genetic information.

It is through changes in the sequence of bases in an organism's DNA - by adding, subtracting, or substituting - that evolution occurs and it is through that process that humans and chimpanzees came to differ.

Scientists believe that humans and chimpanzees diverged from a common ancestor about 6 million years ago. Since that time, both species have continued to evolve, acquiring traits that make them different from both that ancestor and from each other.

Though completing the chimpanzee genome is an achievement in itself, it is the ability to now compare chimpanzee and human DNA side-by-side that has researchers excited.

The differences between the two genetic codes include 35 million sites where DNA base pairs differ and another 5 million sites where a portion of the genetic code - up to thousands of base pairs - has been inserted or deleted.

The comparison is already bearing fruit, revealing areas of rapid change and highlighting areas to target for future research.

Researchers found that the most rapidly changing genes in humans, chimpanzees, and other mammals include those involving reproduction, the sense of smell, and the immune response that protects creatures from infection and disease.

In addition, they found that the genes changing unusually quickly in humans and chimpanzees, compared with other mammals, include those involved in sound perception, nerve signal transmission, and production of sperm.

Among the genes that appear to be evolving more rapidly in humans than in chimpanzees are those called transcription factors. These genes are known to control other genes, including one thought to be involved in the appearance of speech in humans.

The consortium found a small number of genes that have undergone dramatic change, with more than 50 genes in humans missing from chimpanzees, including three key genes involved in inflammation. The absence of those genes in chimpanzees may explain the known differences between chimpanzees and humans in their inflammatory and immune response. In addition, six regions of the human genome appear to have been acquired relatively recently, over the last 250,000 years, and to contain changes so advantageous that they rapidly spread through the population. These areas are prime targets for future research.

"The most concrete result of this work is that we now have this complete catalog - nearly complete catalog - of human-chimp differences," Mikkelsen said. "Both our laboratory and many other laboratories around the world are sifting through these ... to find the relevant, important changes."

Related stories:

  • Variations discovered in human genomes

  • Diving Into The Gene Pool:
    Using DNA data, anthropologist analyzes human roots

  • Finding disease by subtraction:
    Pathologist Matthew Meyerson searches for nonhuman life in humans







  • Copyright 2007 by the President and Fellows of Harvard College