Consequences of Hox gene duplication in the vertebrates: an investigation of the zebrafish Hox paralogue group 1 genes

As a result of a whole genome duplication event in the lineage leading to t eleosts, the zebrafish has seven clusters of Hox patterning genes, rather t han four, as described for tetrapod vertebrates. To investigate the consequ ences of this genome duplication, we have carried nut a detailed comparison of genes from a single Hox paralogue group, paralogue group (PG) 1, We hav e analyzed the sequences, expression patterns and potential functions of al l four of the zebrafish PG1 Hox genes, and compared our data with that avai lable for the three mouse genes. As the basic functions of Hox genes appear to be tightly constrained, comparison with mouse data has allowed us to id entify specific changes in the developmental roles of Hox genes that have o ccurred during vertebrate evolution. We have found variation in expression patterns, amino acid sequences within functional domains, and potential gen e functions both within the PG1 genes of zebrafish, and in comparison to mo use PG1 genes, We observed novel expression patterns in the midbrain, such that zebrafish hoxa1a and hoxc1a are expressed anterior to the domain tradi tionally thought to be under Hox patterning control. The hoxc1a gene shows significant coding sequence changes in known functional domains, which corr elate with a reduced capacity to cause posteriorizing transformations. More over, the hoxb1 duplicate genes have differing functional capacities, sugge sting divergence after duplication. We also find that an intriguing functio n 'shuffling' between paralogues has occurred, such that one of the zebrafi sh hoxb1 duplicates, hoxb1b, performs the role in hindbrain patterning play ed in mouse by the nonorthologous Hoxa1 gene.