Developmental hourglass: Verification by numerical evolution and elucidation by dynamical-systems theory

Abstract Determining the general laws between evolution and development is a fundamental biological challenge. Developmental hourglasses have attracted increased attention as candidates for such laws, but the necessity of their emergence remains elusive. We conducted evolutionary simulations of developmental processes to confirm the emergence of the developmental hourglass and unveiled its establishment. We considered organisms consisting of cells containing identical gene networks that control morphogenesis and evolved them under selection pressure to induce more cell types. By computing the similarity between the spatial patterns of gene expression of two species that evolved from a common ancestor, a developmental hourglass was observed, that is, there was a correlation peak in the intermediate stage of development. The fraction of pleiotropic genes increased, whereas the variance in individuals decreased, consistent with previous experimental reports. Reduction of the unavoidable variance by initial or developmental noise, essential for survival, was achieved up to the hourglass bottleneck stage, followed by diversification in developmental processes, whose timing is controlled by the slow expression dynamics conserved among organisms sharing the hourglass. This study suggests why developmental hourglasses are observed within a certain phylogenetic range of species. Author Summary Understanding the intriguing relationship between development and evolution in multicellular organisms has long been a challenge in biology. A recent hypothesis called the developmental hourglass proposes that there is a conserved middle stage during development across species of the same animal group. Despite growing evidence supporting this hypothesis, the underlying mechanisms and reasons for its emergence have remained elusive due to limited experimental data. To address this gap, we employed numerical evolution of gene regulation networks controlling pattern formation. Remarkably, our simulations revealed that species that diverged relatively recently in phylogeny displayed the highest similarity during the middle stage of development, which gradually diminished as they diverged further phylogenetically. Our findings satisfied not only the criteria of the developmental hourglass but also confirmed several essential characteristics of the developmental hourglass reported in recent experiments. Through theoretical analysis, we further demonstrated that the emergence of the developmental hourglass could be attributed to the acquisition of genes that change slowly and govern developmental processes, which also foster the robustness of development. By integrating computational simulations, theoretical insights, and previous experimental evidence, our study thus provides a comprehensive understanding of the developmental hourglass, which will unravel the intricate relationship between development and evolution.