Citation: Thompson, J. R., Petsios, E., Davidson, E. H., Erkenbrack, E. M., Gao, F., & Bottjer, D. J. (2015). Reorganization of sea urchin gene regulatory networks at least 268 million years ago as revealed by oldest fossil cidaroid echinoid.Scientific reports, 5.
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity Between HOXA11 and FOXO1
Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.
This work provides direct evidence of evolutionary rewiring of gene-regulatory circuitry accompanying divergence of two subclasses of echinoderm, the cidaroid and euechinoid sea urchins. These forms descend from a known common Paleo- zoic ancestor, and their embryos develop differently, offering an opportunity to probe the basic evolutionary process by which clade divergence occurs at the gene-regulatory net- work (GRN) level. We carried out a systematic analysis of the use of particular genes participating in embryonic skeleto- genic cell specification, building on an established euechinoid developmental GRN. This study revealed that the well-known and elegantly configured regulatory circuitry that underlies skeletogenic specification in modern sea urchins is largely a novel evolutionary invention. The results dramatically dis- play extensive regulatory changes in a specific developmental GRN, underlying an incidence of cladistic divergence at the subclass level.
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