title: Evolution of milk oligosaccharides and lactose: a hypothesis.
abstract: Mammalian milk or colostrum contains up to 10% of carbohydrate, of which free lactose usually constitutes more than 80%. Lactose is synthesized within lactating mammary glands from uridine diphosphate galactose (UDP-Gal) and glucose by a transgalactosylation catalysed by a complex of β4-galactosyltransferase and α-lactalbumin (α-LA). α-LA is believed to have evolved from C-type lysozyme. Mammalian milk or colostrum usually contains a variety of oligosaccharides in addition to free lactose. Each oligosaccharide has a lactose unit at its reducing end; this unit acts as a precursor that is essential for its biosynthesis. It is generally believed that milk oligosaccharides act as prebiotics and also as receptor analogues that act as anti-infection factors. We propose the following hypothesis. The proto-lacteal secretions of the primitive mammary glands of the common ancestor of mammals contained fat and protein including lysozyme, but no lactose or oligosaccharides because of the absence of α-LA. When α-LA first appeared as a result of its evolution from lysozyme, its content within the lactating mammary glands was low and lactose was therefore synthesized at a slow rate. Because of the presence of glycosyltransferases, almost all of the nascent lactose was utilized for the biosynthesis of oligosaccharides. The predominant saccharides in the proto-lacteal secretions or primitive milk produced by this common ancestor were therefore oligosaccharides rather than free lactose. Subsequent to this initial period, the oligosaccharides began to serve as anti-infection factors. They were then recruited as a significant energy source for the neonate, which was achieved by an increase in the synthesis of α-LA. This produced a concomitant increase in the concentration of lactose in the milk, and lactose therefore became an important energy source for most eutherians, whereas oligosaccharides continued to serve mainly as anti-microbial agents. Lactose, in addition, began to act as an osmoregulatory molecule, controlling the milk volume. Studies on the chemical structures of the milk oligosaccharides of a variety of mammalian species suggest that human milk or colostrum is unique in that oligosaccharides containing lacto-N-biose I (LNB) (Gal(β1 → 3)GlcNAc, type I) predominate over those containing N-acetyllactosamine (Gal(β1 → 4)GlcNAc, type II), whereas in other species only type II oligosaccharides are found or else they predominate over type I oligosaccharides. It can be hypothesized that this feature may have a selective advantage in that it may promote the growth of beneficial colonic bacteria, Bifidobacteria, in the human infant colon.
authors.affiliation: Department of Animal Hygiene, Graduate School of Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, 080-8555, Japan. urashima@obihiro.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Urashima
authors.forename: K
authors.initials: K
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Messer
mesh_terms: D000818:Animals; D003126:Colostrum / Q000737:chemistry / Q000378:metabolism; D004063:Digestion; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D007768:Lactalbumin / Q000235:genetics* / Q000378:metabolism; D007785:Lactose / Q000737:chemistry* / Q000378:metabolism; D008322:Mammals / Q000235:genetics / Q000502:physiology*; D008892:Milk / Q000737:chemistry* / Q000378:metabolism; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D056692:Prebiotics
chemical_list: D009844:Oligosaccharides; D056692:Prebiotics; D007768:Lactalbumin; D007785:Lactose