What snakes and caecilians have in common? Molecular interaction units and the independent origins of similar morphotypes in Tetrapoda.

Developmental pathways encompass transcription factors and cis-regulatory elements that interact as () units. Independent origins of similar phenotypes likely involve changes in different parts of these units, a hypothesis promisingly tested addressing the evolution of the rib-associated lumbar (RAL) morphotype that characterizes emblematic animals such as snakes and elephants. Previous investigation in these lineages identified a polymorphism in the [] enhancer of the [], which interacts with HOX10 proteins to modulate rib development. Here we address the evolution of units focusing on independent origins of RAL morphotypes. We compiled an extensive database for and HOX10 sequences with two goals: (i) evaluate if the enhancer polymorphism is present in amphibians exhibiting the RAL morphotype and (ii) test a hypothesis of enhanced evolutionary flexibility mediated by units, according to which independent origins of the RAL morphotype might involve changes in either component of the interaction unit. We identified the polymorphism in lineages that diverged around 340 Ma, including Lissamphibia. Independent origins of the RAL morphotype in Tetrapoda involved sequence variation in either component of the unit, confirming that different changes may similarly affect the phenotypic outcome of a given developmental pathway.