Evolutionarily speaking, we are born to make babies. Our bodies and brains don’t fall apart until we come to the end of our child-bearing years. So why are grandmothers, who don’t reproduce and who contribute little to food production, still around and still mentally sound? A new study offers an intriguing genetic explanation.
Scientists have proposed several explanations for why our species lives as long and as healthily as it does. One idea is that grandmothers help out with child rearing. A 1998 study found, for example, that a Hadza group of hunter-gatherers in Tanzania had more babies if grandmothers helped feed their newly-weaned young grandchildren. The researchers speculated this kind of care freed up young mothers to reproduce, and ensured that the caregiver grandmother’s genes were passed on to more young. They called their theory the “grandmother hypothesis.”
But grandmothers need to have all their wits about them to help out in this way, and the new study may explain how this happens. Physician-scientist Ajit Varki and evolutionary biologist Pascal Gagneux of the University of California, San Diego, arrived at the findings accidentally. The pair was studying a gene that helps control the body’s inflammatory and immune response to injury or infection. Previous studies have linked two forms of the gene—CD33—to Alzheimer’s disease. While one CD33 variant, or allele, predisposes a person to the disease, the other appears to protect against it by preventing the formation of protein clumps in the brain.
To learn more about the gene’s lineage, the team compared how prevalent the two versions were in human tissue and in chimpanzees, which—along with bonobos—are our closest living animal relatives. Both humans and chimps had similar levels of the damaging version of CD33, meaning it must be the more ancient of the two variants. However, when the researchers looked at the protective variant, its levels were four times higher in humans than in chimps. This suggests that chimps—which usually die around the time their fertility is coming to an end—have little use for the protective variant. Indeed, chimps don’t seem to suffer from the same type of cognitive decline seen with Alzheimer’s.
The scientists then looked for the frequency of the protective allele in samples from the 1000 Genomes Project, a database of genetic variants found in populations around the world. They found the protective allele across a range of ethnicities, including African, American, Asian, and European.
To see whether the same held for other genes thought to protect against cognitive decline, the researchers examined the 1000 Genomes Project for variants of a gene called APOE, which has been implicated in late-onset Alzheimer’s. They also searched for variants of other genes involved in hypertension, diabetes, and cardiovascular disease. As with CD33, the protective variants occurred across ethnicities, the researchers report online today in the Proceedings of the National Academy of Sciences. They then searched the published genomes of chimpanzees, bonobos, and gorillas, but found no evidence of the gene variants in primates. This suggests that these variants evolved when humans first separated from our primate ancestors.
“Grandmothers are so important, we even evolved genes to protect their minds,” Varki says.
More than 5 million Americans over age 65 have Alzheimer’s. The protective CD33 variant isn’t present in everyone, but scientists say learning more about the gene could lead to new drugs designed to mimic its protective effects, says Rudolph Tanzi, a neurogeneticist at Harvard Medical School in Boston who was not part of this study.
“I think a lot more needs to be done, but it’s very interesting to see that we appear to be selecting for an allele that protects you from a disease that doesn’t strike until decade eight or nine,” says Tanzi, who first identified CD33’s role in Alzheimer’s. “This paper reinforces for me and greatly emphasizes the importance of CD33 not just as one factor in Alzheimer’s but as a major evolutionary factor in natural selection against Alzheimer’s.”
For Kristen Hawkes, a behavioral ecologist at the University of Utah in Salt Lake City whose field studies led to the grandmother hypothesis in 1998, the findings provide key genomic evidence that has been lacking in the field. “These guys have fingered a particular signature for selection for competent performance in old age,” she says. “That’s exciting and powerful.”
