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Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc
- Source :
- Genome Biology and Evolution
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- The enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH) is responsible for the synthesis of N-glycolylneuraminic acid (Neu5Gc), a sialic acid present on the cell surface proteins of most deuterostomes. The CMAH gene is thought to be present in most deuterostomes, but it has been inactivated in a number of lineages, including humans. The inability of humans to synthesize Neu5Gc has had several evolutionary and biomedical implications. Remarkably, Neu5Gc is a xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red meats, may promote inflammation, arthritis, and cancer. Likewise, xenotransplantation of organs producing Neu5Gc can result in inflammation and organ rejection. Therefore, knowing what animal species contain a functional CMAH gene, and are thus capable of endogenous Neu5Gc synthesis, has potentially far-reaching implications. In addition to humans, other lineages are known, or suspected, to have lost CMAH; however, to date reports of absent and pseudogenic CMAH genes are restricted to a handful of species. Here, we analyze all available genomic data for nondeuterostomes, and 322 deuterostome genomes, to ascertain the phylogenetic distribution of CMAH. Among nondeuterostomes, we found CMAH homologs in two green algae and a few prokaryotes. Within deuterostomes, putatively functional CMAH homologs are present in 184 of the studied genomes, and a total of 31 independent gene losses/pseudogenization events were inferred. Our work produces a list of animals inferred to be free from endogenous Neu5Gc based on the absence of CMAH homologs and are thus potential candidates for human consumption, xenotransplantation research, and model organisms for investigation of human diseases.
- Subjects :
- 0301 basic medicine
Xenotransplantation
medicine.medical_treatment
Pseudogene
ved/biology.organism_classification_rank.species
pseudogene
Neu5Gc
Genome
Mixed Function Oxygenases
03 medical and health sciences
chemistry.chemical_compound
Phylogenetics
Genetics
medicine
Animals
Humans
Model organism
Gene
Phylogeny
Ecology, Evolution, Behavior and Systematics
Deuterostome
biology
ved/biology
Molecular Sequence Annotation
CMAH
biology.organism_classification
Biosynthetic Pathways
Sialic acid
030104 developmental biology
chemistry
Neuraminic Acids
Pseudogenes
Research Article
Subjects
Details
- ISSN :
- 17596653
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Genome Biology and Evolution
- Accession number :
- edsair.doi.dedup.....14486a50577f68d8ce3c6eefc4cfb13a