Complete Nucleotide Sequences of Bovine as2- and P-Casein cDNAs: Comparisons with Related Sequences in Other Species’ A

The nucleotide sequences corresponding to bovine crs2and p-casein mRNAs have been determined by cDNA analysis. Both sequences appear to be complete at their 5’ ends. The nucleotide sequence of us2-casein, when compared with the corresponding cavine A sequence, helps to define the boundaries of a large amino acid repeat (-80 residues) whereas comparisons with the nucleotide sequences of rat yand mouse a-casein mRNAs also reveal extensive sequence similarities. An alignment of these four sequences shows that the divergence of their translated regions has been characterized by the duplication and deletion of discrete segments of sequence that probably correspond to exons. A high degree of nucleotide substitution is also found when the four sequences are compared, except for wellconserved leader-peptide and phosphorylation-site sequences and, to a lesser extent, the 5’-untranslated regions. Similar comparison of the bovine and rat p-caseins shows that their divergence has involved a high rate of nucleotide substitution but that no major insertions or deletions of sequence have occurred. The several splice sites that have been defined in the rat P-casein gene are likely to have been conserved in the bovine. The contrasting evolutionary histories of the aand P-casein coding sequences correlate with the distinctive functions of these proteins in the casein micelle system in milk.