Citation: Nnamani, M.C., Ganguly, S. , Erkenbrack, E.M., Lynch, V.J., Mizoue, L.S., Tong, Y., Darling, H.L., Fuxreiter, M., Meiler, J., Wagner, G.P. (2016). A derived allosteric switch underlies the evolution of conditional cooperativity between HOXA11 and FOXO1. Cell Reports, 15(10), P2097-2108.
Cell type phylogenetics informs the evolutionary origin of echinoderm larval skeletogenic cell identity
To inform the evolution of the echinoderm larval skeletogenic cell, we have presented a framework for cell-type phylogenetic analysis that integrates spatial gene expression data with phylogenetic comparative methods to reconstruct ancestral gene expression. The genes we chose to include in our analyses have been studied in numerous echinoderm taxa and occupy crucial nodes of a well characterized gene regulatory network11,35. As the number of model and nonmodel organisms increases in evolutionary developmental biology, comparative analyses of spatial data will depend more on ancestral state reconstructions than on direct comparisons with an outgroup. However, it should be noted that such analyses are limited by several factors, including knowledge of a detailed GRN, invoking interspecies comparisons of development, and obtaining reliable divergence times and phylogenetic trees. The present study is not exempt from these limitations. Indeed, we chose to analyze five genes with broad phylogenetic sampling over twelve taxa. To support our findings, we ran pruned sensitivity analyses and concluded that decreasing the number of taxa reduced our ability to resolve ancestral states with confidence at certain nodes, especially the Asterozoan and Eleutherozoan MRCAs (Supplementary Fig. 12). Therefore, broad phylogenetic sampling is vitally important to resolve ancestral gene expression patterns. One could argue that increasing the number of genes in the analysis would help resolve the question of interest. However, we suggest that whether or not this is true will depend on the case at hand. For instance, in this study we analyzed genes from a GRN where the functional importance of many regulatory genes is well-known. In most cases, a well characterized GRN will not be available, and it will be equally important to possess a broad sampling of taxa across a phylogeny. For instance, as gene expression in early development becomes available in more asterozoans, which are under-sampled with respect to echinozoans in our analyses, we will gain greater confidence in our inferences at the asterozoan and eleutherozoan MRCAs. Indeed, we also see potential for the approach utilized herein to analyze ancestral states of GRN regulatory architecture. For example, the isolation and characterization of homologous cis-regulatory modules, from ATAC-seq, ChIP-seq, and other omics-level endeavors in phylogenetically distant organisms, could be then incorporated with the method presented here to determine which modules are lineage or cell-type specific.
Mechanistic understanding of evolutionary divergence in animal body plans devolves from analysis of those developmental processes that, in forms descendant from a common ancestor, are responsible for their morphological differences. The last common ancestor of the two extant subclasses of sea urchins, i.e., euechinoids and cidaroids, existed well before the Permian/Triassic extinction (252 mya). Subsequent evolutionary divergence of these clades offers in principle a rare opportunity to solve the developmental regulatory events underlying a defined evolutionary divergence process.
© 2016 Eric M Erkenbrack and Cell Press. All rights reserved.