Sialic Acid Recognition by Siglecs

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Human Uniqueness Compared to "Great Apes": 
Likely Difference
Human Universality: 
Individual Universal (All Individuals Everywhere)
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Humans lack the common mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), due to a mutation in CMP-Neu5Ac hydroxylase, which occurred after our evolutionary divergence from great apes. One apparent consequence of human Neu5Gc loss is a domain-specific functional adaptation of Siglec-9, a major member of the family of sialic acid-binding receptors of immune cells that are designated the CD33-related Siglecs (CD33rSiglecs). While recombinant human Siglec-9 showed recognition of both Neu5Ac and Neu5Gc, chimpanzee and gorilla Siglec-9 were found to strongly prefer to bind to Neu5Gc. Probing of multiple endogenous CD33rSiglecs on circulating blood cells suggest that the binding differences observed for Siglec-9 are representative of the other CD33rSiglecs. Thus, the Neu5Ac-binding ability of at least some of the human CD33rSiglecs appears to be a derived state, which was apparently selected for following loss of Neu5Gc in the hominid lineage. In keeping with this, findings suggested ongoing adaptive evolution specific to the sialic acid-binding domain of Siglec-9.


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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