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CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMP-N-acetylneuraminate monooxygenase) pseudogene)

Certainty Style Key
Hover over keys for definitions:
True   Likely   Speculative
What is MOCA?
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Human Uniqueness Compared to "Great Apes": 
Absolute Difference
MOCA Domain: 
Genetics
MOCA Topic Authors: 
Ajit Varki

Sialic acids are sugars typically found at the outer terminal position of glycan chains that cover the surface of all vertebrate cells. The most commonly-expressed sialic acid is N-acetylneuraminic acid (Neu5Ac), which is the precursor for N-glycolylneuraminic acid (Neu5Gc) synthesis -  a conversion mediated by  action of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) enzyme. While both Neu5Ac and Neu5Gc are found to be expressed in many mammals (including our closest evolutionary cousins, the great apes), the single-copy human CMAH gene was pseudogenized by an Alu-mediated deletion event, which seems to have occurred ~2-3 million years ago in our ancestors, and is now universal to the human population. This genetic loss has multiple consequences that are still being investigated, ranging from pathogen susceptibility to changes in the immune system. 

Genetics Topic Attributes

Gene symbols follow the HUGO Gene Nomenclature Committee standard.

Gene Symbol:
CMAH (CMAH)
Type of Human-Specific Changes:
Pseudogenization
Related MOCA Topics
Related Topics:
TitleCertainty
Alpha2-6-linked Sialic Acid ExpressionSpeculative
Increase in Short Interspersed Elements/Alu InsertionsTrue
N-Glycolylneuraminic Acid Expression True
Sialic Acid Content of the BrainSpeculative
Sialic Acid Recognition by Siglecs Likely
Sialoadhesin on Macrophages Speculative
SIGLEC7 (sialic acid binding Ig-like lectin 7 )Speculative
SIGLEC9 (sialic acid binding Ig-like lectin 9)Speculative
Referenced By:
TitleCertainty
Malaria Likely
Milk CompositionTrue
N-Glycolylneuraminic Acid Expression True
Sialic Acid Recognition by Siglecs Likely
Wound HealingLikely
Timing

Timing of Appearance of the Difference in the Hominin Lineage.

For this entry assume that

  • the common ancestor of humans and old world monkeys was 25000 thousand (25 million) years ago
  • the common ancestor of humans and chimpanzees was 6000 thousand (6 million) years ago
  • the emergence of the genus Homo was 2000 thousand (2 million) years ago
  • the common ancestor of modern humans was 100 thousand years ago

 

Possible Appearance: 
4000 Thousand Years
Probable Appearance: 
2000 Thousand Years
Definite Appearance: 
100 Thousand Years
References: 

Chou, H.H., Hayakawa, T., Diaz, S., Krings, M., Indriati, E., Leakey, M., Paabo, S., Satta, Y., Takahata, N., and Varki, A. 2002. Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci U S A. 99:11736-11741.
Hayakawa, T., Aki, I., Varki, A., Satta, Y., and Takahata, N. 2006. Fixation of the Human-Specific CMP-N-Acetylneuraminic Acid Hydroxylase Pseudogene and Implications of Haplotype Diversity for Human Evolution. Genetics. 172:1139-1146.
Hedlund, M., Tangvoranuntakul, P., Takematsu, H., Long, J.M., Housley, G.D., Kozutsumi, Y., Suzuki, A., Wynshaw-Boris, A., Ryan, A.F., Gallo, R.L., Varki, N., and Varki, A. 2007. N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol. 27:4340-4346.
Varki, A. 2009. Multiple changes in sialic acid biology during human evolution. Glycoconj J. 26:231-245.