During human evolution, some genes were lost or silenced from the genome of hominins. These missing genes might be the key to the evolution of humans' unique cognitive skills. An inactivation mutation in CMP-N-acetylneuraminic acid hydroxylase (CMAH) was the result of natural selection. The inactivation of CMAH protected our ancestors from some pathogens and reduced the level of N-glycolylneuraminic acid (Neu5Gc) in brain tissue. Interestingly, the low level of Neu5Gc promoted the development of brain tissue, which may have played a role in human evolution. As a xenoantigen, Neu5Gc may have been involved in brain evolution by affecting neural conduction, neuronal development, and aging.
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http://dx.doi.org/10.1186/s41232-025-00368-3 | DOI Listing |
Biomolecules
February 2025
Laboratorio de Bioquímica, Departamento de Química, Facultad de Ciencias, Universidad de Tarapacá, Arica 1000007, Chile.
Unlabelled: N-Glycolylneuraminic acid (Neu5Gc) is a sialic acid variant commonly found in most mammals but not synthesized by humans due to an inactivating mutation in the CMP-Neu5Ac hydroxylase () gene. Despite this, Neu5Gc-containing molecules are consistently detected in human tissues, particularly in malignant tumors. However, the mechanisms underlying Neu5Gc accumulation and its role in cancer development remain poorly understood.
View Article and Find Full Text PDFInflamm Regen
February 2025
Center of Reproductive Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou, P.R. China.
During human evolution, some genes were lost or silenced from the genome of hominins. These missing genes might be the key to the evolution of humans' unique cognitive skills. An inactivation mutation in CMP-N-acetylneuraminic acid hydroxylase (CMAH) was the result of natural selection.
View Article and Find Full Text PDFTransl Oncol
May 2023
Institute for Glycomics, Griffith University, Gold Coast, Australia. Electronic address:
One of the forms of aberrant glycosylation in human tumors is the expression of N-glycolylneuraminic acid (Neu5Gc). The only known enzyme to biosynthesize Neu5Gc in mammals, cytidine-5'-monophosphate-N-acetylneuraminic acid (CMAH), appears to be genetically inactivated in humans. Regardless, low levels of Neu5Gc have been detected in healthy humans.
View Article and Find Full Text PDFVaccines (Basel)
September 2022
Cronex Inc., Jeju 63078, Korea.
Pigs are promising donors of biological materials for xenotransplantation; however, cell surface carbohydrate antigens, including galactose-alpha-1,3-galactose (α-Gal), N-glycolylneuraminic acid (Neu5Gc), and Sd blood group antigens, play a significant role in porcine xenograft rejection. Inactivating swine endogenous genes, including , , and , decreases the binding ratio of human IgG/IgM in peripheral blood mononuclear cells and erythrocytes and impedes the effectiveness of α-Gal, Neu5Gc, and Sd, thereby successfully preventing hyperacute rejection. Therefore, in this study, an effective transgenic system was developed to target , , and using CRISPR-CAS9 and develop triple-knockout pigs.
View Article and Find Full Text PDFBiology (Basel)
June 2022
Institute of Genome Biology, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Humans frequently interact with pigs, whose meat is also one of the primary sources of animal protein. They are one of the main species at the center of sialic acid (Sia) research. Sias are sugars at terminals of glycoconjugates, are expressed at the cell surfaces of mammals, and are important in cellular interactions.
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