The role of gene duplication in the evolution of vertebrate Hox gene function.

摘要

Gene duplication has long been thought to play a key role in the evolution of gene function, and hence the evolution of morphology. The vertebrate lineage in particular has been shaped by multiple rounds of large-scale gene duplication, leading to the expansion of many well-studied gene families. As a result of a whole-genome duplication in the lineage leading to teleost fish, zebrafish possess additional copies of many genes relative to their tetrapod counterparts. Amongst these are the Hox genes, a conserved family of transcription factors known to play a key role in anterior to posterior pattern formation during animal development. Whereas mouse and human possess 39 Hox genes arranged in four clusters, zebrafish have 48 Hox genes found over seven clusters. We have used one related group of Hox genes (those in paralog group 1) to examine the effects of gene duplication on the evolution of gene function. In the mouse, these genes play a key role in both proper segmentation of the hindbrain and formation of appropriate segmental identity. We find that these hindbrain patterning functions are present in the zebrafish, but are distributed in a different manner amongst the genes of paralog group 1. Thus, it appears that while Hox gene functions have been conserved in distantly related vertebrates, some functions may be played by paralogous rather than orthologous genes. Furthermore, we have uncovered a non-canonical expression for the zebrafish hoxa1a gene in the midbrain, well anterior to the segmented nervous system regions thought to be under Hox control. Comparison of Hoxa1 expression in a range of species reveals that this expression domain is actually conserved among the vertebrates, and had previously been overlooked in both mouse and chick. Thus, these studies have demonstrated a conserved and previously unknown role for Hox genes in the midbrain, and highlight the types of modifications that occur within duplicated gene families.