EVOLUTION OF MOUSE T-BOX GENES BY TANDEM DUPLICATION AND CLUSTER DISPERSION

The T-box genes comprise an ancient family of putative transcription f actors conserved across species as divergent as Mus musculus and Caeno rhabditis elegans. All T-box gene products are characterized by a nove l 174-186-amino acid DNA binding domain called the T-box that was firs t discovered in the polypeptide products of the mouse T locus and the Drosophila melanogaster optomotor-blind gene. Earlier studies allowed the identification of five mouse T-box genes, T, Tbx1-3 and Tbr1, that all map to different chromosomal locations and are expressed in uniqu e temporal and spatial patterns during embryogenesis. Here, we report the discovery of three new members of the mouse T-box gene family, nam ed Tbx4, Tbx5, and Tbx6. Two of these newly discovered genes, Tbx4 and Tbx5, were found to be tightly linked to previously identified T-box genes. Combined results from phylogenetic, linkage, and physical mappi ng studies provide a picture for the evolution of a T-box subfamily by unequal crossing over to form a two-gene cluster that was duplicated and dispersed to two chromosomal locations. This analysis suggests tha t Tbx4 and Tbx5 are cognate genes that diverged apart from a common an cestral gene during early vertebrate evolution.