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Nucleic Acids Research, 1986, Vol. 14, No. 4 1883-1902
© 1986

Articles

Evolution of the casein multigene family: conserved sequences in the 5' flanking and exon regions

Li-yuan Yu-Lee, Lizabeth Richter-Mann, Craig H. Couch, A.Francis Stewart1,+, Anthony G. Mackinlay1 and Jeffrey M. Rosen*

Department of Cell Biology, Baylor College of Medicine One Baylor Plaza, Houston, TX 77030, USA 1School of Biochemistry, University of New South Wales Kensington 2033, Australia

*To whom correspondence should be addressed

Received November 13, 1985. Accepted January 22, 1986.

The rat {alpha}- and bovine {alpha}s1-casein genes have been isolated and their 5' sequences determined. The rat {alpha}-, ß-, {gamma}- and bovine {alpha}s1-casein genes contain similar 5' exon arrangements in which the 5' noncoding, signal peptide and casein klnase phosphorylatlon sequences are each encoded by separate exons. These findings support the hypothesis that during evolution, the family of casein genes arose by a process involving exon recruitment followed by intra-genic and intergenic duplication of a primordial gene. Several highly conserved regions in the first 200 base pairs of the 5' flanking DNA have been identified. Additional sequence homology extending up to 550 base pairs upstream of the CAP site has been found between the rat {alpha}- and bovine {alpha}s1-casein sequences. Unexpectedly, the 5' flanking promoter regions are conserved to a greater extent than both the entire mature coding and intron regions of these genes. These conserved 5' flanking sequences may contain potential cis regulatory elements which are responsible for the coordinate expression of the functionally-related casein genes during mammary gland development.

+Present address: Institute of Cell and Tumor Biology, German Cancer Research Center, D-6900 Heidelberg, FRG


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