Maintenance of functional equivalence during paralogous Hox gene evolution

Biological diversity is driven mainly by gene duplication followed by mutat ion and selection. This divergence in either regulatory or protein-coding s equences can result in quite different biological functions for even closel y related genes. This concept is exemplified by the mammalian Hox gene comp lex, a group of 39 genes which are located on 4 linkage groups, dispersed o n 4 chromosomes(1-4). The evolution of this complex bee;an with amplificati on in cis of a primordial Hox gene to produce 13 members, followed by dupli cations in tuans of much of the entire unit. As a consequence, Hox genes th at occupy the same relative position along the 5' to 3' chromosomal coordin ate (trans-paralogous genes) share more similarity in sequence and expressi on pattern than do adjacent Hox genes on the same chromosome. Studies in mi ce indicate that although individual family members may have unique biologi cal roles, they also share overlapping functions with their paralogues(5-12 ). Here we show that the proteins encoded by the paralogous genes, Hoxa3 an d Hoxd3, can carry out identical biological functions, and that the differe nt roles attributed to these genes are the result of quantitative modulatio ns in gene expression.