Evolution of the large secreted gel-forming mucins

Mucins, the major component of mucus, contain tandemly repeated sequences t hat differ from one mucin to another. Considerable advances have been made in recent years in our knowledge of mucin genes. The availability of the co mplete genomic and cDNA sequences of MUC5B, one of the four human mucin gen es clustered on chromosome 11, provides an exemplary model for studying the molecular evolution of large mucins. The emerging picture is one of expans ion of mucin genes by gene duplications, followed by internal repeat expans ion that strictly preserves frameshift. Computational and phylogenetic anal yses have permitted the proposal of an evolutionary history of the four hum an mucin genes located on chromosome 11 from an ancestor gene common to the human von Willebrand factor gene and the suggestion of a model for the evo lution of the repeat coding portion of the MUC5B gene from a hypothetical a ncestral minigene. The characterization of MUC5B, a member of the large sec reted gel-forming mucin family, offers a new model for the comparative stud y of the structure-function relationship within this important family.