JOZEFOWICZ, C.J.*; MCCLINTOCK, J.M.; PRINCE, V.E.: Duplication and evolution of vertebrate Hox genes: hoxa1a and orthologs

In all metazoan species in which it has been investigated, Hox genes are arranged in clusters, with invertebrates having a single cluster and vertebrates having a minimum of 4 clusters. The four cluster organization, until recently thought typical for all vertebrates, does not incorporate a growing set of data documenting more than four hox clusters in teleosts (zebrafish, medaka, etc.). We are currently examining differences in Hox paralog group (PG) 1 gene deployment between teleosts and other vertebrates in order to test the hypothesis that the duplications leading to increased Hox gene number allowed evolution of new functions for Hox genes in teleosts. Experiments in our lab have established that the zebrafish PG1 genes have not only an altered gene complement as a result of gene duplication (4 PG1 genes as opposed to 3 in mouse), but also differing expression patterns in relation to the murine PG1 genes. It has been assumed that Hox genes are important for patterning hindbrain and more posterior structures, but zebrafish PG1 genes may deviate from this classic model of Hox gene function as they exhibit expression patterns in the developing midbrain. We are investigating PG1 genes in a phylogenetically relevant sample of vertebrates to infer the ancestral osteichthyan condition of midbrain expression. We will discriminate between the opposing hypotheses that (1) teleost midbrain expression is a novelty that evolved after Hox cluster duplications, versus (2) midbrain expression is a primitive condition that has been lost in the mammalian lineage.