Abstract

Hox proteins are part of the conserved superfamily of homeodomain‐containing transcription factors and play fundamental roles in shaping animal body plans in development and evolution. However, molecular mechanisms underlying their diverse and specific biological functions remain largely enigmatic. Here, we have analyzed Hox sequences from the main evolutionary branches of the Bilateria group. We have found that four classes of Hox protein signatures exist, which together provide sufficient support to explain how different Hox proteins differ in their control and function. The homeodomain and its surrounding sequences accumulate nearly all signatures, constituting an extended module where most of the information distinguishing Hox proteins is concentrated. Only a small fraction of these signatures has been investigated at the functional level, but these show that approaches relying on Hox protein alterations still have a large potential for deciphering molecular mechanisms of Hox differential control.