Table 1.
Uniquely human changes in sialic acid biologya
| Gene | Human-Specific Changes | Possible Consequences for Humans |
|---|---|---|
| CMAH | Human-specific Alu-mediated deletion including Exon 6, resulting in frame-shift and truncated inactive enzyme. | Loss of Neu5Gc and excess of Neu5Ac expression on cell surfaces. Effects of pathogen recognition and invasion. Metabolic incorporation of Neu5Gc from dietary sources, despite anti-Neu5Gc antibodies. Potential risk of biotherapeutic products containing Neu5Gc. |
| SIGLEC1 (Sialoadhesin) | Increased Neu5Ac-rich ligands in humans. Enhanced frequency and broader expression pattern in macrophages | Increased likelihood of masking by endogenous Neu5Ac-rich ligands. Altered responses to sialic acid-expressing pathogens? |
| SIGLEC5/14 | Expression suppressed on T Cells. Restoration of “essential arginine residue” for Sia recognition. | Hyper-responsive phenotype of human T cells—a possible role in propensity for diseases associated with T Cell activation? |
| SIGLEC6 | Placental Trophoblast Expression | Expression levels increase with progress of labor. Involved in regulating the tempo of the human birth process? |
| SIGLEC7 and SIGLEC9 | Amino acid changes in the Sia-recognizing domain, allowing Neu5Ac recognition | Altered control of innate immune cell activation? Enhanced susceptibility to Neu5Ac-expressing pathogens? |
| SIGLEC11 | Human-specific gene conversion, diminished binding, with new expression in brain microglia | Altered interactions of microglia with neural cells? Altered response of microglia to infections? |
| SIGLEC12 | Human-specific mutation of “essential arginine residue”, markedly decreasing Sia recognition | Unknown. |
| SIGLEC13 | Human-specific Alu-mediated gene deletion | Unknown |
| SIGLEC16 | Human-specific (?) inactivating mutation | Unknown |
| ST6GAL1 | Increased expression of Siaα2–6Galβ1–4GlcNAcβ1- termini in various cell types | Protection from Avian Influenza virus which prefers Siaα2–3 linkages, and susceptibility to Human Influenza virus which prefers Siaα2–6 linkages |
aModified and updated from ref. [10]. See text for details and for literature references