Complete nucleotide sequences of bovine alpha S2- and beta-casein cDNAs: comparisons with related sequences in other species

The nucleotide sequences corresponding to bovine alpha S2- and beta- caseinmRNAs have been determined by cDNA analysis. Both sequences appear to becomplete at their 5' ends. The nucleotide sequence of alpha S2-casein, whencompared with the corresponding cavine A sequence, helps to define theboundaries of a large amino acid repeat (approximately 80 residues) whereascomparisons with the nucleotide sequences of rat gamma- and mouseepsilon-casein mRNAs also reveal extensive sequence similarities. Analignment of these four sequences shows that the divergence of theirtranslated regions has been characterized by the duplication and deletionof discrete segments of sequence that probably correspond to exons. A highdegree of nucleotide substitution is also found when the four sequences arecompared, except for well-conserved leader-peptide and phosphorylation-sitesequences and, to a lesser extent, the 5'-untranslated regions. Similarcomparison of the bovine and rat beta-caseins shows that their divergencehas involved a high rate of nucleotide substitution but that no majorinsertions or deletions of sequence have occurred. The several splice sitesthat have veen defined in the rat beta-casein gene are likely to have beenconserved in the bovine. The contrasting evolutionary histories of thealpha- and beta-casein coding sequences correlate with the distinctivefunctions of these proteins in the casein micelle system in milk.