β1,4-galactosyltransferase and lactose biosynthesis:: Recruitment of a housekeeping gene from the nonmammalian vertebrate gene pool for a mammary gland specific function

beta 1,4-galactosyltransferase (beta 4GalT-I) is a constitutively expressed trans-Golgi enzyme, widely distributed in vertebrates, which synthesizes the beta 4-N-acetyllactosamine structure commonly found in glycoconjugates. In mammals beta 4GalT-I has been recruited for a second biosynthetic function, the production of lactose; this function takes place exclusively in the lactating mammary gland. In preparation for lactose biosynthesis, beta 4GalT-I enzyme levels are increased significantly. We show that mammals have evolved a two-step mechanism to achieve this increase. In step one there is a switch to the use of a second transcriptional start site, regulated by a stronger, mammary gland-restricted promoter. The transcript produced is distinguished from its housekeeping counterpart by the absence of similar to 180 nt of 5'-untranslated sequence. In step two, this truncated transcript is translated more efficiently, relative to the major transcript expressed in all other somatic tissues.