Protein glycosylation--an evolutionary crossroad between genes and environment.
The majority of molecular processes in higher organisms are performed by various proteins and are thus determined by genes that encode these proteins. However, a significant structural component of at least half of all cellular proteins is not a polypeptide encoded by a single gene, but an oligosaccharide (glycan) synthesized by a network of proteins, resulting from the expression of hundreds of different genes. Relationships between hundreds of individual proteins that participate in glycan biosynthesis are very complex which enables the influence of environmental factors on the final structure of glycans, either by direct effects on individual enzymatic processes, or by induction of epigenetic changes that modify gene expression patterns. Until recently, the complexity of glycan structures prevented large scale studies of protein glycosylation, but recent advances in both glycan analysis and genotyping technologies, enabled the first insights into the intricate field of complex genetics of protein glycosylation. Mutations which inactivate genes involved in the synthesis of common N-glycan precursors are embryonically lethal. However, mutations in genes involved in modifications of glycan antennas are common and apparently contribute largely to individual phenotypic variations that exist in humans and other higher organisms. Some of these variations can be recognized as specific glyco-phenotypes that might represent specific evolutionary advantages or disadvantages. They are however, amenable to environmental influences and are thus less pre-determined than classical Mendelian mutations.
Lauc
Gordan
G
Genos Ltd, Glycobiology Division, Planinska 1, 10000 Zagreb, Croatia. glauc@genos.hr
Zoldoš
Vlatka
V
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002236:Carbohydrate Conformation; D004777:Environment; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D005796:Genes; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics
D006023:Glycoproteins; D011134:Polysaccharides