A COMBINED ANALYSIS OF GENOMIC AND PRIMARY-PROTEIN STRUCTURE DEFINES THE PHYLOGENETIC RELATIONSHIP OF NEW MEMBERS OF THE T-BOX FAMILY

T-box genes form an ancient family of putative transcriptional. regula tors characterized by a region of homology to the DNA-binding domain o f the murine Brachyury (T) game product, This T-box domain is conserve d from Caenorhabditis elegans to human, and mutations is T-box genes h ave been associated with developmental defects in Drosophila, zebrafis h, mice, and humans. Here we report the identification of three novel murine T-box genes saki an investigation of their evolutionary relatio nship to previously known family members by studying the genomic struc ture of the T-box. All T-box genes from nematodes to humans possess a characteristic central intron that presumably was inherited from a com mon ancestral precursor. Two additional intron positions are also cons erved with the exception of two nematode T-box genes, Subsequent intro n insertions, potential. deletions, and/or intron sliding formed a str uctural basis for the divergence into distinct subfamilies and a subst rate for length variations of the T-box domain, In mice, the 11 T-box genes known to date can be grouped into seven subfamilies. Genes assig ned to the same subfamily by genomic structure show related expression patterns, We propose a model for the phylogenetic relationships withi n the gene family that provides a rationale for classifying new T-box genes and facilitates interspecific comparisons. (C) 1998 Academic Pre ss.