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

Abstract

The rat alpha- and bovine alpha s1-casein genes have been isolated and their 5' sequences determined. The rat alpha-, beta-, gamma- and bovine alpha s1-casein genes contain similar 5' exon arrangements in which the 5' noncoding, signal peptide and casein kinase phosphorylation 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 intragenic 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.

Mineralized tissue and vertebrate evolution: The secretory calcium-binding phosphoprotein gene cluster

“…The ␣-and ␤-caseins are termed Ca-sensitive, because they precipitate in the presence of Ca ions but are stabilized in colloidal suspension by their interaction with the Ca-insensitive -casein (6). Ca-sensitive casein genes (CSN) arose from a common origin by gene duplication (7,8).…”

A Comparative Study of the 5' Flanking Sequences of the .ALPHA.S1- and .BETA.-Casein Genes: Human and Other Mammalian Species.

“…The exon-intron boundary of the human CSN1 gene followed the GT/AG rule and was highly homologous with the consensus sequences [12]. Human CSN1 and CSN2 genes sequences characterized in this study show high homology with those of other mammalian species, including cattle [11,13], goats [14], mice [15], rabbits [16,17], rats [18,19] and sheep [20] and possess 60-71% and 64-73% homology with those of other mammalian species. Furthermore, the nucleotide sequences of the regions between positions -200 and -1 of human CSN1 and CSN2 genes are highly conserved with those of other mammalian casein genes.…”

Complete Nucleotide Sequence of the Bovine ß-casein Gene

“…The isolation and identification from a AEMBL3 library of clones with bovine casein genomic inserts has previously been described (Yu- Lee et al 1986). Large scale preparation, by plate lysis, and purification of A-clone DNA were essentially as described by Maniatis et al (1982).…”

“…Screening of the bovine genomic library as previously described (Yu- Lee et al 1986) led to the isolation of two clones that hybridized specifically to the bovine iJ-casein cDNA pBiJC468 (Stewart et al 1987). Upon restriction analysis, these two clones, ABiJC8 and ABiJCI2, were found to be independent but overlapping clones and both clones were found to hybridize to end-labelled restriction fragments representative of the entire mRNA.…”

“…The sequence of the rat i3-casein gene plus its flanking regions (Jones et al 1985) and the 5' flanking sequences of the rat a-, "(-and bovine asrcasein genes have been published (Yu-Lee et at. 1986).…”