Protein Evolution by Molecular Tinkering: Diversification of the Nuclear Receptor Superfamily from a Ligand-Dependent Ancestor

Bridgham, Jamie T.; Eick, Geeta; Larroux, Claire; Deshpande, K. Y.; Harms, Michael J.; Gauthier, Marie; Ortlund, Eric A.; Degnan, Bernard M.

doi:10.1371/journal.pbio.1000497

Cited by 221 publications

(259 citation statements)

References 52 publications

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“…(c) Nuclear receptor signalling [83,84]; thus, the expansive diversity in this group of proteins may have evolved with the independent origins of numerous diverse ligand binding capabilities [85]. Unlike the other cell signalling mechanisms discussed here, NRs act as both the receptor and the effector molecule, providing the most direct link between the extracellular signal and the transcriptional response.…”

Section: (B) Canonical Wnt Signallingmentioning

confidence: 99%

“…Baker [88] also described an oestrogen-related receptor (family NR3) from T. adhaerens but indicated that it contained a hormone binding pocket that was too small to accommodate a hormone, suggesting it may not function the way NR3 family receptors do in bilaterians. Among sponges, two NRs have been identified from Amphimedon queenslandica, Suberites domuncula and Oscarella carmela-one, NR2, appears to be an orthologue of HNF4 and is found only in A. queenslandica and O. carmela; the second, apparently sponge-specific, is found in A. queenslandica, S. domuncula and O. carmela [85,91]. Three NR orthologues have been identified from ctenophores (two from M. leidyi and one from P. bachei), all of which appear to be orthologues of the NR2 family but none of which has a canonical DNA binding domain.…”

Section: (B) Canonical Wnt Signallingmentioning

confidence: 99%

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Phylogenetic evidence for the modular evolution of metazoan signalling pathways

Babonis¹,

Martindale²

2017

Phil. Trans. R. Soc. B

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One contribution of 17 to a theme issue 'Evo-devo in the genomics era, and the origins of morphological diversity'. Communication among cells was paramount to the evolutionary increase in cell type diversity and, ultimately, the origin of large body size. Across the diversity of Metazoa, there are only few conserved cell signalling pathways known to orchestrate the complex cell and tissue interactions regulating development; thus, modification to these few pathways has been responsible for generating diversity during the evolution of animals. Here, we summarize evidence for the origin and putative function of the intracellular, membrane-bound and secreted components of seven metazoan cell signalling pathways with a special focus on early branching metazoans (ctenophores, poriferans, placozoans and cnidarians) and basal unikonts (amoebozoans, fungi, filastereans and choanoflagellates). We highlight the modular incorporation of intra-and extracellular components in each signalling pathway and suggest that increases in the complexity of the extracellular matrix may have further promoted the modulation of cell signalling during metazoan evolution. Most importantly, this updated view of metazoan signalling pathways highlights the need for explicit study of canonical signalling pathway components in taxa that do not operate a complete signalling pathway. Studies like these are critical for developing a deeper understanding of the evolution of cell signalling.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.

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Section: (B) Canonical Wnt Signallingmentioning

confidence: 99%

Section: (B) Canonical Wnt Signallingmentioning

confidence: 99%

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

Babonis¹,

Martindale²

2017

Phil. Trans. R. Soc. B

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“…Indeed, it was not an easy task, as the MR was the last cloned receptor from the adrenal and sex steroid receptor family, which also includes the glucocorticoid receptor (GR), progesterone receptor (PR), androgen receptor (AR) and estrogen receptor (ER) (Evans 1988, Markov et al 2009. The MR and other steroid receptors belong to the nuclear receptor family, a diverse group of transcription factors that arose in multicellular animals, which have key roles in the physiology of humans and other vertebrates (Markov et al 2009, Bridgham et al 2010, Huang et al 2010, Baker et al 2013. A 3-ketosteroid receptor (SR) ancestor of the MR, GR, PR and AR first 234:1 appears in amphioxus, a close ancestor of vertebrates , Paris et al 2008, Markov et al 2009, Katsu et al 2010.…”

Section: Introductionmentioning

confidence: 99%

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function

Baker

Katsu

2017

Journal of Endocrinology

119

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The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimeras. Skate MR has a strong response to corticosteroids that are mineralocorticoids and glucocorticoids in humans. The half-maximal responses (EC50s) for skate MR for the mineralocorticoids aldosterone and 11-deoxycorticosterone are 0.07 nM and 0.03 nM, respectively. EC50s for the glucocorticoids cortisol and corticosterone are 1 nM and 0.09 nM, respectively. The physiological mineralocorticoid in ray-finned fish, which do not synthesize aldosterone, is not fully understood because several 3-ketosteroids, including cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone and progesterone are transcriptional activators of fish MR. Further divergence of the MR and GR in terrestrial vertebrates, which synthesize aldosterone, led to emergence of aldosterone as a selective ligand for the MR. Here, we combine sequence analysis of the CR and vertebrate MRs and GRs, analysis of crystal structures of human MR and GR and data on transcriptional activation by 3-ketosteroids of wild-type and mutant MRs and GRs to investigate the evolution of selectivity for 3-ketosteroids by the MR in terrestrial vertebrates and ray-finned fish, as well as the basis for binding of some glucocorticoids by human MR and other vertebrate MRs.

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“…To date, only a small number of ASR studies have included in vivo evaluation of inferred ancestral proteins and these have related to functionality rather than fitness (e.g. transcriptional response to different ligands [Bridgham et al 2006[Bridgham et al , 2009[Bridgham et al , 2010Eick et al 2012), ability to rescue different phenotypes (Finnigan et al 2012), ability to confer resistance to b-lactams (Risso et al 2013)]. In this study, we utilise our previously reconstructed ancestral LeuB enzymes to investigate the organismal fitness conferred by these inferred ancestral enzymes in relation to their favourable biochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

et al. 2015

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Ancestral sequence reconstruction has been widely used to study historical enzyme evolution, both from biochemical and cellular perspectives. Two properties of reconstructed ancestral proteins/enzymes are commonly reported-high thermostability and high catalytic activity-compared with their contemporaries. Increased protein stability is associated with lower aggregation rates, higher soluble protein abundance and a greater capacity to evolve, and therefore, these proteins could be considered ''superior'' to their contemporary counterparts. In this study, we investigate the relationship between the favourable in vitro biochemical properties of reconstructed ancestral enzymes and the organismal fitness they confer in vivo. We have previously reconstructed several ancestors of the enzyme LeuB, which is essential for leucine biosynthesis. Our initial fitness experiments revealed that overexpression of ANC4, a reconstructed LeuB that exhibits high stability and activity, was only able to partially rescue the growth of a DleuB strain, and that a strain complemented with this enzyme was outcompeted by strains carrying one of its descendants. When we expanded our study to include five reconstructed LeuBs and one contemporary, we found that neither in vitro protein stability nor the catalytic rate was correlated with fitness. Instead, fitness showed a strong, negative correlation with estimated evolutionary age (based on phylogenetic relationships). Our findings suggest that, for reconstructed ancestral enzymes, superior in vitro properties do not translate into organismal fitness in vivo. The molecular basis of the relationship between fitness and the inferred age of ancestral LeuB enzymes is unknown, but may be related to the reconstruction process. We also hypothesise that the ancestral enzymes may be incompatible with the other, contemporary enzymes of the metabolic network.

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Protein Evolution by Molecular Tinkering: Diversification of the Nuclear Receptor Superfamily from a Ligand-Dependent Ancestor

Abstract: Phylogenetic reconstruction of the structure and function of the ancestor of the nuclear receptor protein family reveals how functional diversity evolves by subtle tinkering with an ancestral template.

Cited by 221 publications

References 52 publications

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function

Reconstructed Ancestral Enzymes Impose a Fitness Cost upon Modern Bacteria Despite Exhibiting Favourable Biochemical Properties

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