• Share

A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity Between HOXA11 and FOXO1
Citation: Erkenbrack, E. M., Ako-Asare, K., Miller, E., Tekelenburg, S., Thompson, J. R., & Romano, L. (2016). Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms. Development Genes and Evolution, 226(1), 37-45.
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.

More Publications

Evolutionary rewiring of gene regulatory network linkages at divergence of the echinoid subclasses

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.

Divergence of ectodermal and mesodermal gene regulatory network linkages in early development of sea urchins

Developmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in the early development of euechinoid sea urchins have revealed that little appreciable change has occurred since their divergence ∼90 million years ago (mya). These observations suggest that strong conservation of GRN architecture was maintained in early development of the sea urchin lineage. Testing whether this holds for all sea urchins necessitates comparative analyses of echinoid taxa that diverged deeper in geological time. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here I report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral–aboral patterning of nonskeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. These results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids, developmental GRNs have undergone significant, cell type–biased alterations.
© 2016 Eric M Erkenbrack and Cell Press. All rights reserved.