Structure and function of milk protein genes.

Interspecies comparisons of cDNA and mosaic milk protein genes have confirmed their high rate of evolution, but the overall gene organization has been conserved. The three Ca-sensitive casein genes, which share common motifs in the promoter region and contain similar sequences that encode signal peptide and multiple phosphorylation sites, probably derived from a common ancestor. alpha s1- and alpha s2-casein genes, divided into many small exons, undergo complex splicing, and the deleted caseins arise from exon skipping. The four bovine casein genes are clustered on 200 kb of chromosome 6. alpha-Lactalbumin and beta-lactoglobulin pseudogenes occur in ruminants. Study of the expression of native and modified milk protein genes in mammary cell lines and transgenic animals and DNA footprinting have shown the occurrence of important regulatory motifs in the proximal 5' flanking region, including one recognized by a specific mammary nuclear factor. Good stage- and tissue-specific expression has been obtained in transgenic animals with milk protein genes having less than a 3-kb 5' flanking region. Better knowledge of both the structure and function of milk protein genes, which has already allowed the use of powerful techniques for the rapid identification of alleles, offers the potential for the genetic modification of milk composition.