Sialic Acid-expressing Pathogens

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Human Uniqueness Compared to "Great Apes": 
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Sialic acids are major cell surface sugars involved in many biological functions in the Deuterostome lineage of animals (Vertebrates and so-called "higher" invertebrates.  In contrast they are rarely found in other branches of life.  A striking exception is the expression of sialic acids on certain pathogens, which use convergent evolutionary mechanisms to display sialic acids in vertebrate-like patterns, thereby eluding the immune system is a variety of ways.  Remarkably, the majority of such sialic-acid expressing pathogens known to date are either human-specific or human-specialized.  For various reasons, ascertainment basis seems an unlikely explanation  Interestingly, pathogens cannot reinvent the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) , but can do so with the human-enriched sialic acid N-acetylneuraminic acid (Neu5Ac). One possible explanation is that these organisms are thus "taking advantage" of this human-specific change in sialic acid evolution, by displaying the human Neu5Ac sialic acid and "hijacking" the intrinsic inhibitory functions of certain human innate immune cell Siglecs that have undergone evolutionary changes to recognize Neu5Ac, since the human-specific loss of Neu5Gc, about 2-3 million years ago. Of note, many of these pathogens lethally infect human fetuses, neonates and infants, often involving the brain, and were thus likely selective forces in human evolution.  Interestingly, Siglec-11 expression in microglia is also a uniquely human condition.  Perhaps brain-invading sialic acid pathogens iteract with this Siglec? Overall, it is reasonable to suggest that sialic acid pathogens have evolved to take advantage of the unusual sialic acid biology of humans.

Timing

Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Possible Appearance: 
3,000 thousand years ago
Probable Appearance: 
2,000 thousand years ago
Definite Appearance: 
100 thousand years ago

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