Loss of N-glycolylneuraminic acid in humans: Mechanisms, consequences, and implications for hominid evolution

Evolution of human-chimpanzee differences in malaria susceptibility: Relationship to human genetic loss of N -glycolylneuraminic acid

“…Thus, the loss of Neu5Gc in the human lineage sometime after the initial mutation Ϸ3 mya (36) might have provided our emerging Homo ancestors with temporary relief from this form of malaria. However, the loss of Neu5Gc expression also led to a marked increase in its precursor, Neu5Ac (35). Thus, we suggest that P. falciparum emerged later, through selective evolution of its EBA-175, toward preferentially recognizing the Neu5Ac-rich erythrocytes of humans (i.e., P. falciparum evolved from a strain of ancestral P. reichenowi that adapted to this radical change in the human ''sialome'').…”

“…Thus, we chose to focus on the binding specificity of PfEBA-175 and P. reichenowi (Pr)EBA-175 as a potential explanation for the striking host specificities of P. falciparum and P. reichenowi by using the corresponding Pf͞PrEBA-140 molecules as controls. A major biochemical change in Sia biology occurred in the human lineage after divergence from our common ancestor with chimpanzees (35,36). The most common mammalian Sias are N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac), Neu5Ac being the metabolic precursor of Neu5Gc.…”

“…The most common mammalian Sias are N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac), Neu5Ac being the metabolic precursor of Neu5Gc. Humans cannot produce Neu5Gc from Neu5Ac because of a mutation in the CMAH gene (35). Thus, although human erythrocytes show no overall loss of Sias, they express no Neu5Gc and a great excess of the precursor, Neu5Ac (37).…”

Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration

“…N-Glycolylneuraminic acid (Neu5GC) is a sialic acid molecule found on the cells of most mammals (except humans), and almost all humans develop anti-Neu5GC antibodies due to exposure to Neu5GC from different sources, including animal meat consumption. 17 It is therefore possible that these antibodies may have been responsible for the observed complement activation by in vitro propagated human MSCs, if the cells took up Neu5GC during culture. To examine whether Neu5GC was present on in vitro propagated human MSCs, we incubated MSCs from five donors with fish gelatin (blocking), then stained them with chicken antiNeu5GC IgY antibodies and fluorescein isothiocyanate (FITC)-labeled anti-IgY antibodies and examined the staining by flow cytometry.…”

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

“…Varki et al reported a genetic deficiency of the enzyme CMAH in humans that is not present in hominoid apes (Varki, 2001). Due to this deficiency humans are unable to synthesize Neu5GC anywhere in their whole body, while chimpanzees produce it in all body cells except the CNS.…”