Comparative transcriptomics in serial organs uncovers early and pan-organ developmental changes associated with organ-specific evolutionary novelty

Abstract We know that morphogenesis evolves along with final morphologies, but have little integrated understanding of morphogenesis evolution, except for old principles such as recapitulation and heterochronies. To revisit such principles, we monitored the developmental dynamics of mouse and hamster molars by combining transcriptome timeseries and morphological quantifications. The mouse upper molar evolved a new dental plan with two more cusps. They form last in mouse upper molar, recapitulating their appearance in the fossil record, but divergence in transcriptome dynamics is already visible in early stages. Three corresponding early developmental changes, including heterochronies and changes in cell proportions, combine and result in a new developmental trajectory culminating with the late addition of two cusps. The biggest surprise came from the lower molar, which was initially included as an additional control, but whose developmental trajectories evolved as much as upper molar’s. Their transcriptome dynamics markedly co-evolved, including spatio-dynamic aspects of cusp formation which are obviously involved in the new upper molar phenotype. Hence upper molar innovation relies in part on non-specific changes which impact morphogenesis in a concerted manner in both molars, but have little impact on lower molar phenotype. This counter-intuitive observation was confirmed in bat limbs. By bridging concerted transcriptomic evolution with concerted evolution of developmental mechanisms, our study introduces a principle for the evolution of organ-specific morphological innovation, with early and pan-organ developmental changes. This changes our expectations on the underlying genetic evolution, and highlights the important role of developmental drift in one organ to accommodate adaptation in another.