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Abstract Molecular studies of animal regeneration typically focus on conserved genes and signaling pathways that underlie morphogenesis. To date, a holistic analysis of gene expression across animals has not been attempted, as it presents a suite of problems related to differences in experimental design and gene homology. By combining orthology analyses with a novel statistical method for testing gene enrichment across large data sets, we are able to test whether tissue regeneration across animals shares transcriptional regulation. We applied this method to a meta-analysis of six publicly available RNA-Seq data sets from diverse examples of animal regeneration. We recovered 160 conserved orthologous gene clusters, which are enriched in structural genes as opposed to those regulating morphogenesis. A breakdown of gene presence/absence provides limited support for the conservation of pathways typically implicated in regeneration, such as Wnt signaling and cell pluripotency pathways. Such pathways are only conserved if we permit large amounts of paralog switching through evolution. Overall, our analysis does not support the hypothesis that a shared set of ancestral genes underlie regeneration mechanisms in animals. After applying the same method to heat shock studies and getting similar results, we raise broader questions about the ability of comparative RNA-Seq to reveal conserved gene pathways across deep evolutionary relationships. 

Abstract Cnidarians—the phylum including sea anemones, corals, jellyfish, and hydroids—are one of the oldest groups of predatory animals. Nearly all cnidarians are carnivores that use stinging cells called cnidocytes to ensnare and/or envenom their prey. However, there is considerable diversity in cnidocyte form and function. Tracing the evolutionary history of cnidocytes may therefore provide a proxy for early animal feeding strategies. In this study, we generated a time‐calibrated molecular clock of cnidarians and performed ancestral state reconstruction on 12 cnidocyte types to test the hypothesis that the original cnidocyte was involved in prey capture. We conclude that the first cnidarians had only the simplest and least specialized cnidocyte type (the isorhiza) which was just as likely to be used for adhesion and/or defense as the capture of prey. A rapid diversification of specialized cnidocytes occurred through the Ediacaran (~654–574 million years ago), with major subgroups developing unique sets of cnidocytes to match their distinct feeding styles. These results are robust to changes in the molecular clock model, and are consistent with growing evidence for an Ediacaran diversification of animals. Our work also provides insight into the evolution of this complex cell type, suggesting that convergence of forms is rare, with the mastigophore being an interesting counterexample.