Uniquely human evolution of sialic acid genetics and biology
Open Access
- 5 May 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (supplement), 8939-8946
- https://doi.org/10.1073/pnas.0914634107
Abstract
Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene–environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the “Human Condition.” Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of α2–6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel “xeno-auto-antigen” situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative “hot spot” of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.Keywords
This publication has 104 references indexed in Scilit:
- Sialic acids acquired by Pseudomonas aeruginosa are involved in reduced complement deposition and siglec mediated host‐cell recognitionFEBS Letters, 2009
- The energetic significance of cookingJournal of Human Evolution, 2009
- A dietary non-human sialic acid may facilitate hemolytic-uremic syndromeKidney International, 2009
- Meat Intake and MortalityJAMA Internal Medicine, 2009
- Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxinNature, 2008
- Human uniqueness: genome interactions with environment, behaviour and cultureNature Reviews Genetics, 2008
- Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cellsNature, 2007
- Siglecs and their roles in the immune systemNature Reviews Immunology, 2007
- Convergent adaptation of human lactase persistence in Africa and EuropeNature Genetics, 2006
- MHC class I molecules and kirs in human history, health and survivalNature Reviews Immunology, 2005