Did Tripper give us grandparents?


Did Tripper give us grandparents?

Neisseria gonorrhoeae bacteria may have driven the evolution of human gene variants that protect against dementia. Photo credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Researchers at the University of California San Diego School of Medicine previously found a number of human gene mutations that protect older adults from cognitive decline and dementia. In a new study published July 9, 2022 in molecular biology and evolution, they focus on one of those mutated genes and try to trace its evolution—when and why it appeared in the human genome. The results suggest that selective pressure from infectious pathogens such as gonorrhea may have promoted the emergence of this gene variant in Homo sapiens and unintentionally encouraged the existence of grandparents in human society.

The biology of most animal species is optimized for reproduction, often at the expense of future health and longer lifespans. In fact, humans are one of the few species known to live well past menopause. According to the “grandmother hypothesis,” older females provide important support in raising human infants and children, who require more care than the young of other species. Scientists are now trying to understand what features of human biology enable this longer-term health.

When researchers previously compared the genomes of humans and chimpanzees, they found that humans have a unique version of the gene for CD33, a receptor expressed in immune cells. The standard CD33 receptor binds to a type of sugar called sialic acid, which is coated on all human cells. When the immune cell senses the sialic acid via CD33, it recognizes the other cell as part of the body and does not attack it, preventing an autoimmune response.

The CD33 receptor is also expressed in the brain’s immune cells called microglia, where it helps control neuroinflammation. However, microglia also play an important role in clearing damaged brain cells and amyloid plaques associated with Alzheimer’s disease. By binding to the sialic acids on these cells and plaques, regular CD33 receptors actually repress this important microglial function and increase the risk of dementia.

This is where the new gene variant comes into play. At some point along the evolutionary line, humans have incorporated an additional mutant form of CD33 that lacks the sugar-binding site. The mutated receptor no longer responds to sialic acids on damaged cells and plaques, allowing microglia to break them down. In fact, higher levels of this CD33 variant have been found to protect against late-onset Alzheimer’s disease.

In an attempt to understand when this gene variant first emerged, co-senior author Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine, and colleagues found evidence of a strong positive selection, suggesting that something was driving the gene to evolve faster than expected. They also discovered that this particular version of CD33 was not present in the genomes of Neanderthals or Denisovans, our closest evolutionary relatives.

“For most of the genes that are different in humans and chimpanzees, Neanderthals usually have the same version as humans, so that was really surprising to us,” Varki said. “These results suggest that the wisdom and nurturing of healthy grandparents may have been an important evolutionary advantage we held over other ancient hominin species.”

Did Tripper give us grandparents?

When Siglecs like CD33 sense human sialic acids, they inhibit the immune cell’s response, even when those acids are on bacteria. Photo credit: UC San Diego Health Sciences

Varki co-led the study with Pascal Gagneux, Ph.D., a professor of pathology at the UC San Diego School of Medicine and a professor in the Department of Anthropology. The authors said the study provides new evidence supporting the grandmother hypothesis.

Still, evolutionary theory says that reproductive success is the main driver of genetic selection, not postreproductive cognitive health. So what drove the prevalence of this mutated form of CD33 in humans?

One possibility, the authors suggest, is that highly contagious diseases such as gonorrhea, which can adversely affect reproductive health, may have influenced human evolution. Gonorrhea bacteria coat themselves with the same sugars that CD33 receptors bind to. Like a wolf in sheep’s clothing, the bacteria are able to trick human immune cells into not identifying them as outside invaders.

The researchers suspect that the mutated version of CD33 without a sugar binding site arose as a human adaptation against such “molecular mimicry” of gonorrhea and other pathogens. In fact, they confirmed that one of the human-specific mutations was able to completely disrupt the interaction between the bacteria and CD33, which would allow immune cells to attack the bacteria again.

Overall, the authors believe humans originally inherited the mutated form of CD33 to protect against gonorrhea in reproductive age, and this gene variant was later co-opted by the brain for its anti-dementia benefits.

“It is possible that CD33 is one of many genes that are selected early in life for their survival advantages against infectious pathogens, but are then secondarily selected for their protective effects against dementia and other age-related diseases,” Gagneux said.

Co-authors include Sudeshna Saha, Naazneen Khan, Andrea Verhagen, Aniruddha Sasmal, and Sandra Diaz of UC San Diego; Troy Comi and Joshua M. Akey at Princeton University; Hai Yu and Xi Chen from UC Davis and Martin Frank from Biognos AB.

How a protein in your brain might protect against Alzheimer’s disease

More information:
Sudeshna Saha et al, Evolution of human-specific alleles protecting grandmothers’ cognitive function, molecular biology and evolution (2022). DOI: 10.1093/molbev/msac151

Provided by the University of California – San Diego

Citation: Did Tripper give us grandparents? (2022, July 18) Retrieved July 18, 2022 from https://phys.org/news/2022-07-gonorrhea-granparents.html

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