Human evolution: changes in sialic acid changed immunity (Introduction)

by David Turell , Saturday, July 25, 2020, 18:35 (1364 days ago) @ David Turell

We are not immune to some infectious agents apes and others are immune to by a change in this acid which coats cells. It may have altered human evolution. See the bold:

https://www.sciencemag.org/news/2020/07/ancient-microbial-arms-race-sharpened-our-immun...

"Nissi Varki noted that humans suffer from a long list of deadly diseases—including typhoid fever, cholera, mumps, whooping cough, measles, smallpox, polio, and gonorrhea—that don’t afflict apes and most other mammals. All of those pathogens follow the same well-trodden pathway to break into our cells: They manipulate sugar molecules called sialic acids. Hundreds of millions of these sugars stud the outer surface of every cell in the human body—and the sialic acids in humans are different from those in apes.

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"By analyzing modern human genomes and ancient DNA from our extinct cousins, the Neanderthals and Denisovans, the researchers detected a burst of evolution in our immune cells that occurred in an ancestor of all three types of human by at least 600,000 years ago.

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"The arena for this evolutionary arms race is the glycocalyx, a sugar coating that protects the outer membrane of all cells. It consists of a forest of molecules that sprout from the cell membrane. The sialic acids are at the tip of the tallest branches, sugar chains called glycans, which are rooted to fats and proteins deeper in the membrane.

"Given their prominence and sheer number, sialic acids are usually the first molecules that invading pathogens encounter. Human cells are coated with one type of sialic acid, N-acetylneuraminic acid (Neu5Ac). But apes and most other mammals also carry a different one, N-glycolylneuraminic acid (Neu5Gc).

"More than 2 million years ago, according to multiple molecular clock methods, a mutation in the CMAH gene on chromosome six made it impossible for human ancestors to produce Neu5Gc anymore; instead, they made more of another sialic acid, Neu5Ac. “We now know we had an ancient complete makeover of the surface of the human cells,” says evolutionary biologist Pascal Gagneux of UCSD, a co-author of the new paper. Birds, some bats, ferrets, and New World monkeys all separately made the same evolutionary change.

"The change likely evolved as a defense against malaria, says UCSD physician-scientist Ajit Varki, senior author of the paper and Nissi Varki’s spouse. Malarial parasites that infect chimpanzees were no longer able to bind with the altered sialic acids on our red blood cells.

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In past studies, Ajit Varki and Gagneux suggested the makeover of the cell and the loss of Neu5Gc may have even contributed to the origin of a new species in our genus Homo. If a woman with only Neu5Ac sialic acids mated with a man who still expressed Neu5Gc, her immune system may have rejected that man’s sperm or the fetus that developed from it. This fertility barrier might have helped divide Homo populations into different species more than 2 million years ago, the researchers speculated. (my bold)

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"But the sialic acid change also sparked a new arms race between pathogens and our ancestors. In the new study, the researchers scanned DNA for immune genes in six Neanderthals, two Denisovans, and 1000 humans, and looked at dozens of chimps, bonobos, gorillas, and orangutans as well. They found evolutionary changes that “markedly altered” one class of proteins—sialic acid-binding immunoglobulin-type lectins, or Siglecs—that usually sit on the surface of human immune cells and recognize sialic acids.

"Siglecs are molecular sentries: They probe sialic acids to see whether they are familiar parts of our own bodies or foreign invaders. If Siglecs spot sialic acids that are damaged or missing, they signal immune cells to activate, rousing an inflammatory army to attack potential invaders or clean up damaged cells. If sialic acids instead appear to be normal parts of our own cells, other, inhibitory Siglecs throttle back immune defenses so as not to attack our own tissues

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"Although the recently mutated Siglecs protect us from pathogens, they may also contribute to other diseases. Some of the genetically changed Siglecs are associated with inflammation and autoimmune disorders such as asthma and with meningitis. The researchers suggest the altered Siglecs may be constantly on high alert and do not dampen immune responses against our own tissues;

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“'This nicely shows that … natural selection is not always going for the optimal solution, because the optimal solution is changing all the time,” says Rita Gerardy-Schahn, a glycobiologist...who was not part of the new work. “What is best for natural selection in the short run may be the wrong selection tomorrow.'”

Comment: The last comment demonstrates that the battle with pathogens is a constantly changing arena of struggle. Note the bold. A mutational error favored by natural selection or by God may have arranged for our human evolution.