MOLECULAR EVOLUTION OF HOX GENE-REGULATION - CLONING AND TRANSGENIC ANALYSIS OF THE LAMPREY HOXQ8 GENE

The mammalian Hox clusters arose by duplication of a primordial cluste r. The duplication of Hox: clusters created redundancy within cognate groups, allowing for change in function over time. The lamprey, Petrom yzon marinus, occupies an intermediate position within the chordates, both in terms of morphologic complexity and possibly cluster number. T o determine the extent of divergence among Hox genes after duplication events within vertebrates, we analyzed Hox genes belonging to cognate group 8. Here we report characterization of the HoxQ8 gene, which sho ws conservation with mammalian genes in its amino-terminal, homeobox a nd hexapeptide sequences, and in the position of its splice sites. A b eta-galactosidase reporter gene was introduced in the HoxQ8 genomic re gion by targeted recombinational cloning using a yeast-bacteria shuttl e vector, tor, pClasper. These reporter gene constructs were tested fo r their ability to direct region-specific expression patterns in trans genic mouse embryos. Lamprey enhancers direct expression to posterior neural tube but not to mesoderm, suggesting conservation of neuronal e nhancers. In the presence of the mouse heat shock promoter, lamprey en hancers could also direct expression to the posterior mesoderm suggest ing that there has been some divergence in promoter function. Our resu lts suggest that comparative studies on Hox: gene structure and analys is of regulatory elements may provide insights into changes concomitan t with Hox cluster duplications in the chordates. (C) 1998 Wiley-Liss, Inc.