Mammalian homeobox-containing genes: genome organization, structure, expression and evolution.

Mammalian homeo box-containing genes have been isolated by their sequence similarity to Drosophila homeotic selector genes. About 20 murine homeo box genes have been identified to date and their expression and structural organization has been described in detail. Most homeo box gene loci are organized in at least three major gene clusters in the mouse and human genome. The structure of homeo box genes within these clusters is very similar and in this paper the murine Hox-2.2 gene will be discussed as an example. Homeo box genes are expressed in region-specific patterns during different stages of vertebrate development and almost all mammalian homeo box genes are expressed in the central nervous system (CNS) of the developing embryo. Within the developing CNS of mouse embryos the anterior boundaries of expression are specific for each gene. Comparisons of nucleotide and amino acid sequences as well as the analysis of the structural organization of murine and human homeo box genes reveal strong paralogous relationships between genes in different clusters. These findings suggest that the homeo box gene clusters evolved in two steps. First, an ancestral gene cluster was created by duplications of individual genes along one linkage group and in a subsequent step duplications of the ancestral gene complex gave rise to the three (or possibly four) gene clusters observed in mouse and human to date. The possibility of the homeo box genes representing a functional array of genetic switches will be discussed.