Ubiquitous systems drift in the evolution of development

Developmental systems drift (DSD) is a process where a phenotypic trait is conserved over evolutionary time, while the genetic basis for the trait changes. DSD has been identified in models with simpler genotype-phenotype maps (GPMs), however the extent of DSD in more complex GPMs, such as developmental systems, is debated. To investigate the occurrence of DSD in complex developmental GPMs, we constructed a multi-scale computational model of the evolution of gene regulatory networks (GRNs) governing plant meristem (stem cell niche) development. We found that, during adaptation, some regulatory interactions became essential for the correct expression of stem cell niche genes. These regulatory interactions were subsequently conserved for thousands of generations. Nevertheless, we observed that these deeply conserved regulatory interactions could be lost over the extended period of neutral evolution. These losses were compensated by changes elsewhere in the GRN, which then became conserved as well. This gain and loss of regulatory interactions resulted in a continual cis-regulatory rewiring in which accumulated changes caused changes in the expression of several genes. Using two publicly available datasets we confirmed the prevalence of cis-regulatory changes across six evolutionary divergent plant species, and showed that these changes do not necessarily impact gene expression patterns, demonstrating the occurrence of DSD. These findings align with the results from our computational model, showing that DSD is pervasive in the evolution of complex developmental systems. Statement of significance A key open question in evo-devo research is the evolvability of complex phenotypes: to which extent is neutral or beneficial change hindered by deleterious mutations? We investigated the potential for developmental systems drift (DSD) in plant development using a computational evo-devo model. We found that the regulatory interactions between genes changed extensively, resulting in the continual neutral rewiring of the gene regulatory network underpinning development. Even regulatory interactions that were essential for correct development were replaced over long evolutionary time scales. Using plant genome and gene expression data from two publicly available datasets, we found high turnover of cis-regulatory elements without consistent change in gene expression, confirming the widespread occurrence of DSD as predicted by our model.