Web Exclusives: Genetics

Comparing Genomes to Find What Makes Us Human
By Alisa Zapp Machalek
Posted May 21, 2009

The three billion letters of DNA in the human genome are more than 98 percent identical to those of a chimpanzee.

What's the difference between you and a chimp? Genetically speaking, virtually nothing.

The tiny genetic difference between us and our nearest animal relatives is responsible for our nimble hands, unique voice boxes and larger brains. Together, these characteristics enable us to speak and understand language, develop music and art, and build skyscrapers, supercomputers, and space shuttles.

To better understand the function of our uniquely human DNA, Katherine Pollard, a biostatistician at the Gladstone Institutes at University of California, San Francisco, wrote a computer program to identify DNA sequences that differ between chimps and us. To pick out the bits of DNA found only in humans, Pollard's program also examined the genetic sequences of the mouse, rat and chicken.

The complete DNA sequence, or genome, of humans is composed of about three billion "letters"—the chemical units abbreviated A, T, G or C. The genomes of humans and chimpanzees are about 98.5 percent identical. Still, the difference adds up to more than 30 million letters.

To compare all those letters, and, millions of others from the mouse, rat and chicken genomes, Pollard needed to create an extraordinarily powerful computational tool. She spent months developing, debugging and refining a program that could flip through more than 2,000 DNA letters per second.

Once it was ready, Pollard ran the program on a massive computer cluster at the University of California, Santa Cruz. After just two days, the program generated a ranked list of the DNA sequences that vary the most between humans and chimpanzees.

Katherine Pollard, a biostatistician at the Gladstone Institutes at University of California, San Francisco. Credit: Michael McColl

At the top of the list was a bit of DNA only 118 letters long.

Pollard and her colleague looked up the DNA sequence in a public genomic database and found that it had not been named or actively studied. They also noticed that some experiments indicated that the sequence was active in human brain cells.

"We both yelled 'Awesome!' at the same time," Pollard remembers. They had realized that the tiny piece of DNA might play a key role in the formation of humankind's most treasured trait—our brains.

Pollard named the region HAR1 for Human Accelerated Region 1 because it appears to be a section of DNA that changed rapidly after chimps and humans diverged from a common ancestor. Unlike most of our genetic material, the HAR1 sequence differs dramatically from that of chimps.

Pollard and her collaborators strongly suspect that HAR1 is involved in the formation of the wrinkled outermost brain layer called the cerebral cortex. This part of the brain plays a key role in consciousness, thought, language, memory and attention.

As Pollard and her coworkers continue to study HAR1, they learn about other DNA differences between chimps and humans. For example, the second chunk of DNA on her ranked list, dubbed HAR2, seems to be involved in prenatal development of our wrists and thumbs. She and other scientists suspect it could help explain why humans have greater hand dexterity, enabling us to make and use complicated tools.

Pollard has also found human-specific DNA changes in a gene, called FOXP2, that ensures the proper development of brain regions necessary for human speech. Still other gene sequences seem to explain differences in the digestive systems of humans and chimps.

In addition to helping us compare and understand various species, this sort of research may help advance human health. For example, chimps don't get AIDS. If we could figure out what makes them genetically immune to the virus, maybe we could find a way to help vaccinate people against it.

Interestingly, many of the important genetic differences between humans and chimps appear in sections of DNA, like HAR1, that do not code for proteins. Scientists once called these regions "junk DNA." Now the work of Pollard and many others is revealing they may actually be a powerful part of the genome.