Genetic polymorphism of caseins: a tool to investigate casein micelle organization.

摘要

The unusual and complex polymorphism, detected at the alphas1-casein locus, is partly responsible for the large individual variability observed in the casein content of goat milk, and for its poor clotting ability. Structural analyses performed at the protein and subsequently at the nucleotide levels have provided an understanding of the molecular basis of this genetic polymorphism and prompted the speculation that it might be exploited to improve, through selection, cheesemaking properties of goatmilk. So far, at least 13 alleles have been described at this locus. They are distributed into 7 classes of protein variants (alphas1-casein A to alphas1-casein G) of which some appear to be internally deleted, associated with 4 levels of expression ranging between 0 (alphas1-casein O) and 3.5 g/litre (alphas1-casein A, B and C)/allele. The large deletion (37 amino acid residues) occurring within variant F removes a highly hydrophilic part of the molecule including a cluster of 5 phosphoseryl residuesinvolved in interactions, through colloidal calcium phosphate, between submicelle units. Such an event is not without any effect on the organization and the physicochemical properties of the micelle, particularly in terms of size and calcium content. Mutations responsible for this genetic polymorphism have been identified, thus having allowed the development of genotyping procedures based on the polymerase chain reaction technique. Morphological observations performed at the cellular level, on mammary tissue sections have revealed that goats homozygous for the defective alleles (alphas1-casein E, F, G and O) display epithelial cells with swelling of the rough endoplasmic reticulum primarily due to an accumulation of proteins, that strongly suggests a dysfunction in secretion mechanisms. A defective allele has been also found, in the goat, at the beta-casein locus (beta-casein O) which makes this species, with its highly polymorphic casein system, a valuable and unique tool to investigate casein micelle organization.