β1,4-Galactosyltransferase and Lactose Biosynthesis: Recruitment of a Housekeeping Gene from the Nonmammalian Vertebrate Gene Pool for a Mammary Gland Specific Function

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Abstract
β1,4-galactosyltransferase (β4GalT-I)is a constitutively expressed trans-Golgi enzyme, widelydistributed in vertebrates, which synthesizes theβ4-N-acetyllactosamine structure commonly found in glycoconjugates. In mammals β4GalT-Ihas been recruited for a second biosynthetic function,the production of lactose; this function takes placeexclusively in the lactating mammary gland. Inpreparation for lactose biosynthesis, β4GalT-I enzymelevels are increased significantly. We show that mammalshave evolved a two-step mechanism to achieve thisincrease. In step one there is a switch to the use of a second transcriptional start site,regulated by a stronger, mammary gland-restrictedpromoter. The transcript produced is distinguished fromits housekeeping counterpart by the absence of 180 nt of 5′-untranslated sequence. In step two,this truncated transcript is translated moreefficiently, relative to the major transcript expressedin all other somatic tissues.