Molecular Divergence of Lysozymes and α-Lactalbumin

Abstract

The vast number of proteins that sustain the currently living organisms have been generated from a relatively small number of ancestral genes that has involved a variety of processes. Lysozyme is an ancient protein whose origin goes back an estimated 400 to 600 million years. This protein was originally a bacteriolytic defensive agent and has been adapted to serve a digestive function on at least two occasions, separated by nearly 40 million years. The origins of the related goose type and T4 phage lysozyme that are distinct from the more common C type are obscure. They share no discernable amino acid sequence identity and yet they possess common secondary and tertiary structures. Lysozyme C gene also gave rise, after gene duplication 300 to 400 million years ago, to a gene that currently codes for alpha-lactalbumin, a protein expressed only in the lactating mammary gland of all but a few species of mammals. It is required for the synthesis of lactose, the sugar secreted in milk. alpha-Lactalbumin shares only 40% identity in amino acid sequence with lysozyme C, but it has a closer spatial structure and gene organization. Although structurally similar, functionally they are quite distinct. Specific amino acid substitutions in alpha-lactalbumin account for the loss of the enzyme activity of lysozyme and the acquisition of the features necessary for its role in lactose synthesis. Evolutionary implications are as yet unclear but are being unraveled in many laboratories.

The evolution of milk secretion and its ancient origins

“…It has been apparent for many years -from amino acid sequence similarity, three-dimensional structure and the structure of the exons that code for a-lactalbumin -that a-lactalbumin is most closely related to c-type lysozyme and is derived from it via gene duplication and base pair substitution (Prager and Wilson, 1988;Qasba and Kumar, 1997;Brew, 2003). The estimated date of origin of a-lactalbumin from c-lysozyme is ancient, before the time of the split of synapsids from sauropsids approximately 310 mya (Prager and Wilson, 1988).…”

“…Many authors have been puzzled by this date, as it was assumed that mammary glands did not arise until the appearance of 'early mammals' (i.e. mammaliaforms) 100 million or more years later (Hayssen and Blackburn, 1985;Prager and Wilson, 1988;Qasba and Kumar, 1997;Messer and Urashima, 2002), but it is consistent with an ancient origin of lactation.…”

Cloning and characterization of an invertebrate type lysozyme from Venerupis philippinarum

“…Based on the differences in structural, catalytic and immunological characters, lysozymes found so far are generally classified into six distinct types: chicken-type (c-type) lysozyme, goose-type (gtype) lysozyme, invertebrate-type (i-type) lysozyme, phage lysozyme, bacterial lysozyme and plant lysozyme (Bachali et al, 2002(Bachali et al, , 2004Fastrez, 1996;Beintema and Terwisscha van Scheltinga, 1996;Hikima et al, 2003;Hultmark, 1996;Ito et al, 1999;Jollès and Jollès, 1984;Liu et al, 2006;Nilsen and Myrnes, 2001;Olsen et al, 2003;Prager, 1996;Qasba and Kumar, 1997). Unlike g-type and c-type lysozyme, i-type lysozyme is a novel family found solely in invertebrate.…”

“…Specifically, the enzyme catalyzes the cleavage of the glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine in bacterial peptidoglycan, and causes cell lysis (Prager and Jollès, 1996;Qasba and Kumar, 1997). It has been widely accepted that lysozyme functioned as important digestive enzymes in some animals, especially for filter-feeding organisms (Nilsen et al, 1999;Xue et al, 2007).…”

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

“…Lysozime presents a bactericide action against gram-positive bacteria, such as Micrococus lisodeikticus, catalyzing the hydrolysis of 1,4-b junctions between N-acetylmuramic acid and N-acetyl-Dglucosamine in the main chain of peptidoglycans of cell membrane (Burman et al, 1991;Qasba and Kumar, 1997). This protein is secreted by the main and accessories lacrymal glands, representing 25% of total proteins in the tear film.…”