Stanford Magazine - November/December 2011

Stone Age Gene Swap
Sex with Neanderthals
gave modern humans an
immune boost.

FINDINGS

BY KRISTIN SAINANI

When the Neanderthals and other prehistoric human cousins went extinct around 30,000 years ago, they didn’t disappear completely. A little part of them lives on in many of us.

In 2010, scientists revealed that sporadic couplings between our ancestors and the Neanderthals (as well as a related group, the Denisovans) left many of us with traces of their DNA in our genomes. But the evolutionary impact was unclear. Now a team of scientists —led by Peter Parham, professor of structural biology and of microbiology and immunology—has shown that these genetic exchanges significantly strengthened modern human immune systems.

“This is really the first evidence that there was something functional that was contributed from this admixture that was useful for modern humans,” says Laurent Abi-Rached, a research associate in Parham’s lab and first author on the report in Science.

Parham has long suspected that some immune genes might have an ancient origin. He studies the Class I human leukocyte antigen genes (HLA-A, HLA-B and HLA-C), which are known for their role in transplant rejection and for their incredible diversity. Each HLA gene comes in hundreds or thousands of versions, called alleles; two unrelated people rarely have the exact same set. This diversity provides a safety net against extinction, because HLA proteins vary in their ability to fight different pathogens. For example, some people who carry an HLA-B* 57 allele can keep an HIV infection in check without drugs. “That tells us that if we didn’t have modern medicine, somebody would survive. It would be a major cull, but somebody would survive,” Parham says. HLA diversity is so important that it may even influence mate selection: Studies show that people are attracted to the scents of prospective sexual partners with disparate HLA types.

In 1993, while sequencing HLA genes, Parham came across a
mysterious variant: HLA-B* 73. “It stood out like a sore thumb,” he
says. Unlike other HLA alleles, HLA-B* 73 resembled genes found
in chimpanzees and gorillas, suggesting that it was at least 16 mil-
lion years old (predating the split between humans and chimpan-
zees). But it had surprisingly little diversity in people, suggesting

that it had been evolving only a
short time. It was as if an ancient
gene had recently been dropped
into the human gene pool. The
most likely explanation: Modern
humans picked up the gene from
a single mating between Homo sapiens and a related subspecies.
There was no way to prove this theory, however, and it conflicted
with the dominant think-
ing of the time—which was
that our ancestors had
replaced, but never mated
with, archaic humans.
Then, last year, techno-
logical advances allowed
scientists to sequence the
genomes of three Neanderthal females who lived in Croatia more
than 40,000 years ago. They found that Europeans and Asians, but
not Africans, can trace 1 to 4 percent of their heritage to Neander-
thals. Thus, modern humans likely bred with Neanderthals as they
migrated out of Africa 50,000 to 80,000 years ago. “It wasn’t a
massive intermingling. It was probably more on the edges and
at certain times,” Parham says. But it’s not surprising that it
occurred, he adds. “All the data you can glean from the modern
human population is that whenever related populations come