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
National Institutes of Health
In an earlier study, researchers at the University of California - San Diego (UCSG), showed that a set of mutant genes help protect older adults against cognitive decline and dementia. Now the same team has shown that we may have evolved with these mutation as an evolutionary adaptation to the sexually-transmitted disease organism, Neisseria gonorrhoeae that causes gonorrhoea.
These mutations are only found in Homo sapiens and not in our close extinct relatives, Neanderthals and Denisovans, who share the same genes with our common ancestors, the chimpanzees, suggesting that these mutations only became widespread in the H. sapiens genome after we split from our common ancestor with Neanderthals and Denisovans (possibly H. erectus) a few hundred thousand years ago.
The implication of that is that having adults that survived longer and who could be actively involved in child-care of their grandchildren, may have been what gave us an advantage over the archaic hominins we came into contact with, both in Africa and in Eurasia.
The finding is an example of how a mutation which became fixed in the species genome in response to environmental pressure can then be adapted further for an entirely different purpose. The research also shows how the scientists were in no doubt at all about the power of the Theory of Evolution by Natural Selection to explain what we observe in biology. There is no sign of even a shadow of doubt about the TOE or any sign that the TOE is a theory in crisis, as Creationist frauds are continually telling their credulous dupes. The TOE is fundamental to any understanding of biology for anyone who knows anything about it.
Here is how the research is explained in the UCSG news release:
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 only species known to live well past menopause. According to the “grandmother hypothesis,” this is because older women 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 make this longer-term health possible.
When researchers previously compared human and chimpanzee genomes, 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 that all human cells are coated with. 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 brain immune cells called microglia, where it helps control neuroinflammation. However, microglia also have an important role in clearing away 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 suppress this important microglial function and increase the risk of dementia.
This is where the new gene variant comes in. Somewhere along the evolutionary line, humans picked up an additional mutated form of CD33 that is missing the sugar-binding site. The mutated receptor no longer reacts to sialic acids on damaged cells and plaques, allowing the microglia to break them down. Indeed, higher levels of this CD33 variant were independently found to be protective against late-onset Alzheimer’s.When Siglecs like CD33 sense human sialic acids, they inhibit the immune cell’s response, even if those acids are located on bacteria.
In trying 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 strong positive selection, suggesting something was driving the gene to evolve more rapidly 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 genes that are different in humans and chimps, Neanderthals usually have the same version as the humans, so this was really surprising to us. These findings suggest the wisdom and care of healthy grandparents may have been an important evolutionary advantage that we had over other ancient hominin species.
Professor Ajit Varki, MD, co-senior author
Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine,
Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center
University of California San Diego, San Diego, California, USA
Varki led the study with Pascal Gagneux, PhD, professor of pathology at UC San Diego School of Medicine and professor in the Department of Anthropology. The authors said the study provides new evidence supporting the grandmother hypothesis.
Still, evolutionary theory says reproductive success is the main driver of genetic selection, not post-reproductive cognitive health. So what was pushing the prevalence of this mutated form of CD33 in humans?
One possibility, suggest the authors, is that highly infectious diseases like gonorrhea, which can be detrimental to reproductive health, might have impacted human evolution. Gonorrhea bacteria coat themselves in the same sugars that CD33 receptors bind to. Like a wolf in sheep’s clothing, the bacteria are able to trick human immune cells to not identify them as outside invaders.It is possible that CD33 is one of many genes selected for their survival advantages against infectious pathogens early in life, but that are then secondarily selected for their protective effects against dementia and other aging-related diseases.
Professor Pascal Gagneux, PhD, co-senior author
Departments of Medicine, Pathology, Anthropology and Cellular and Molecular Medicine
Center for Academic Research and Training in Anthropogeny and Glycobiology Research and Training Center
University of California San Diego, San Diego, California, USA
The researchers suggest that the mutated version of CD33 without a sugar-binding site emerged as a human adaptation against such “molecular mimicry” by gonorrhea and other pathogens. Indeed, they confirmed that one of the human-specific mutations was able to completely abolish the interaction between the bacteria and CD33, which would allow immune cells to attack the bacteria again.
Altogether, the authors believe humans initially inherited the mutated form of CD33 to protect against gonorrhea during reproductive age, and this gene variant was later co-opted by the brain for its benefits against dementia.
Copyright: © 2022 The authors.Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. Open access. (CC BY 4.0)
AbstractAs I said above, the only scientific theory capable of explaining something such as modern humans having a mutant form of a gene that is present in all out close evolutionary relatives but from which are particular allele is absent, is the Theory of Evolution by Natural Selection.
The myelomonocytic receptor CD33 (Siglec-3) inhibits innate immune reactivity by extracellular V-set domain recognition of sialic acid (Sia)-containing “self-associated molecular patterns” (SAMPs). We earlier showed that V-set domain-deficient CD33-variant allele, protective against late-onset Alzheimer’s Disease (LOAD), is derived and specific to the hominin-lineage. We now report multiple hominin-specific CD33 V-set domain mutations. Due to hominin-specific, fixed loss-of-function mutation in the CMAH gene, humans lack N-glycolylneuraminic acid (Neu5Gc), the preferred Sia-ligand of ancestral CD33. Mutational analysis and MD-simulations indicate that fixed change in amino acid 21 of hominin V-set domain and conformational changes related to His45 corrected for Neu5Gc-loss by switching to N-acetylneuraminic acid (Neu5Ac)-recognition. We show that human-specific pathogens Neisseria gonorrhoeae and Group B Streptococcus selectively bind huCD33 as part of immune evasive molecular mimicry of host SAMPs and that this binding is significantly impacted by amino acid 21 modification. In addition to LOAD-protective CD33 alleles, humans harbor derived, population-universal, cognition-protective variants at several other loci. Interestingly, 11 of 13 SNPs in these human genes (including CD33) are not shared by genomes of archaic hominins: Neanderthals and Denisovans. We present a plausible evolutionary scenario to compile, correlate and comprehend existing knowledge about huCD33-evolution and suggest that grandmothering emerged in humans.
Sudeshna Saha, Naazneen Khan, Troy Comi, Andrea Verhagen, Aniruddha Sasmal, Sandra Diaz, Hai Yu, Xi Chen, Joshua M Akey, Martin Frank, Pascal Gagneux, Ajit Varki
Evolution of Human-specific Alleles Protecting Cognitive Function of Grandmothers
Molecular Biology and Evolution, 2022;, msac151, DOI: 10.1093/molbev/msac151
Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
And of course, this is a beneficial mutation of the sort that Michael J Behe keeps telling his dupes can't exist, because they would be detrimental and thefore 'devolutionary'.
That Creationists fail to understand the explanatory power of the TOE and also fail to understand that, under the glare of the spotlight science is shining on it, it is their childish superstition that is in crisis as it has no predictive power and no supporting evidence. As their favourite guru, Michael J Behe, was forced to admit under oath on the Kitzmiller case, there are no peer-reviewed studies supporting his invention of the notion of intelligent design, and so, according to his own standards, should be discarded as a viable alternative to science.
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