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Big brains vs. strong immunity: Genes hint at evolutionary tug of war

A skull from an ancient specimen of Homo sapiens (foreground, right) is compared with a Neanderthal's skull at the Smithsonian's National Museum of Natural History in Washington. Researchers suggest that a gene linked to the immune system played a roundabout role in brain evolution.
A skull from an ancient specimen of Homo sapiens (foreground, right) is compared with a Neanderthal's skull at the Smithsonian's National Museum of Natural History in Washington. Researchers suggest that a gene linked to the immune system played a roundabout role in brain evolution.Mandel Ngan / AFP - Getty Images file

Scientists say our genes contain the hints of an evolutionary tug of war that took place in the wombs of our ancestors, balancing the drive to bigger brains with the need for a strong immune system.

The push and pull of these genetic variants apparently became more pronounced after pre-humans branched off from the ancestors of chimpanzees, according to biologists Peter Parham of Stanford University and Ashley Moffett of the University of Cambridge.

Two years ago, Parham and other researchers suggested that interbreeding with now-extinct cousins such as Neanderthals and Denisovans may have given early humans a boost of immunity. Parham says the same kind of cross-species hanky-panky may have played a role in the genetic diversity that he and Moffett discuss in a paper published online by Nature Reviews Immunology.

"It quite nicely dovetails with all this other stuff," Parham told NBC News. "There is an inherent instability in the way the underlying mechanism works."

How natural killers work

The two biologists focus on how particular types of white blood cells, known as natural killer cells, work in the human immune system. In addition to fighting infections and tumors, natural killer cells help regulate the growth of the placenta during pregnancy. Humans are unique among primates in having two variants of the genes that control the receptors for natural killer cells.

"B haplotypes are favored during reproduction. A haplotypes are more specialized toward defending against infections," Parham explained. "These are subtle effects. On average, if you're an individual that has two A haplotypes and no B haplotype, you're going to have a slightly more robust immune system in terms of dealing with disease."

Having two B haplotypes, in contrast, would allow for a more robust placenta. That would provide the fetus in the womb with more of the nutrients needed to grow a bigger brain. "In the course of human evolution, you had the evolution of these B haplotypes, which really did enable the brain to get bigger. ... There are correlations between the size of the brain of the baby and these genetic factors," Parham said.

A detailed analysis of human genetic diversity suggests that the genes for the B haplotype emerged in the time frame lasting from about 7 million years ago to 1.7 million years ago. That would cover a period starting with the divergence of human and chimp ancestors, and ending with the human migration out of Africa.

The A-vs.-B breakdown is found in all present-day human populations, suggesting that both variants were important to have for different situations. Parham and Moffett speculate that the A variant was important when a population was facing a disease epidemic, while the B variant became important for brain-building once the epidemic passed.

The role of the birth canal

When our ancestors began walking upright, that introduced another push-pull effect for brain size. "It's difficult to document, but it's generally thought in the field of obstetrics that birthing is more difficult for humans than it is for other species," Parham said. The dimensions and layout of the human birth canal is one constraint: If a baby's skull were to get significantly bigger, it wouldn't fit through the canal.

Another constraint is pregnancy's effect on the mother's cardiovascular system. In some situations, a potentially fatal condition known as preeclampsia can occur.

"Part of the compromise is that the human population has tolerated a certain amount of death in childbirth, due to obstructed labor or preeclampsia. ... Both of these types of death in childbirth have been quite common in our species, as has been documented in so many 19th-century novels," Parham said.

The genetic record indicates that the human species passed through a series of "bottlenecks" in prehistoric times that reduced population diversity to perilously low levels. That's where interbreeding with Neanderthals could have played a part. "One way that modern humans replenished the genetic diversity lost in populations was through the selection of new variants ... another, and possibly more effective, mechanism was to acquire old variants by mating with archaic humans," Parham and Moffett write.

Today, modern medicine has leveled the evolutionary playing field. But in ancient times, all these genetic and physiological factors seem to have interacted to make our brains what they are today.

"Basically, we've got the nervous system and the brain putting pressure on the immune system and the reproductive system," Parham said.

More about human evolution:

Alan Boyle is's science editor. Connect with the Cosmic Log community by "liking" the log's Facebook page, following @b0yle on Twitter and adding the Cosmic Log page to your Google+ presence. To keep up with Cosmic Log as well as's other stories about science and space, sign up for the Tech & Science newsletter, delivered to your email in-box every weekday. You can also check out "The Case for Pluto," my book about the controversial dwarf planet and the search for new worlds.