Shared rules of development predict patterns of evolution in vertebrate segmentation

Phenotypic diversity is not uniformly distributed, but how biased patterns of evolutionary variation are generated and whether common developmental mechanisms are responsible remains debatable. High-level ‘rules’ of self-organization and assembly are increasingly used to model organismal development, even when the underlying cellular or molecular players are unknown. One such rule, the inhibitory cascade, predicts that proportions of segmental series derive from the relative strengths of activating and inhibitory interactions acting on both local and global scales. Here we show that this developmental design rule explains population-level variation in segment proportions, their response to artificial selection and experimental blockade of putative signals and macroevolutionary diversity in limbs, digits and somites. Together with evidence from teeth, these results indicate that segmentation across independent developmental modules shares a common regulatory ‘logic’, which has a predictable impact on both their short and long-term evolvability.