Nuclear Receptor Genes: Evolution (original) (raw)
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Evolution and Diversification of the Nuclear Receptor Superfamilya
Annals of the New York Academy of Sciences, 1998
Nuclear receptors play an important part in the regulation of cell growth and differentiation by providing a direct link between signaling molecules and the transcriptional response. 1 These receptors are grouped into a large superfamily which includes receptors for steroid hormones, vitamin D, ecdysone, retinoic acids (alltrans or 9-cis isoforms), or thyroid hormones. It was recently discovered that fatty acids, farnesol, or prostaglandin J 2 metabolites may act through binding to nuclear receptors. In addition to these receptors for known ligands, an increasing number of "orphan" receptors have been described. It is not yet known if all of these orphan receptors indeed have a ligand still to be identified, if they act in a constitutive manner, or if they have an alternative transcriptional regulation mechanism. To date, the family of nuclear receptors contains more than 60 members. The modular organization of nuclear receptors, the various degrees of conservation between their respective domains, and the importance of nuclear receptors for many physiological processes in both arthropods and vertebrates have led several authors to study these molecules from an evolutionary point of view. Molecular phylogeny studies have led to a classification of the family into three subfamilies:
Nuclear Hormone Receptors and Evolution
Integrative and Comparative Biology, 1999
SYNOPSIS. The nuclear receptor (NR) superfamily includes, in addition to ligandactivated transcription factors, members called orphan receptors, for which no ligand has yet been identified. Phylogenetic analysis shows that the nuclear receptor superfamily can be split into six subfamilies. Interestingly, there appears to be no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. For example, RAR and RXR, which both recognize retinoids, belong to two different subfamilies, suggesting an independence between the evolutionary history of the receptors and their ligand binding abilities. A PCR screen for the presence of NR genes in several phyla of early-and nonmetazoan organisms suggests that NR are specific to metazoans and also reveals that the NR genes in Hydra or Anemonia appear to be limited to homoiogues of orphan receptors. Taken together these data suggest that the first members of the superfamily were probably orphan receptors that later on gained the ability to bind a ligand. Finally, we observed that SmFTZ-Fl and SmRXR are expressed at different levels along the life cycle of the parasitic flatworm Schistosoma mansoni.
Ligand binding and nuclear receptor evolution
BioEssays, 2000
Nuclear receptors form a superfamily of ligand-activated transcription factors that regulate various physiological functions, from development to homeostasis, in metazoans. The superfamily contains not only receptors for known ligands but also a large number of so-called orphan receptors for which ligands do not exist or have not been identified. The evolution of ligand-binding capacity of nuclear receptors may involve either secondary loss in orphan receptors, or evolutionary acquisition of ligand-binding capacity in liganded receptors. In this review, we present arguments from phylogenetic, functional and structural studies that support the hypothesis that there have been several independent gains of ligand-binding ability of nuclear receptors during metazoan evolution.
Molecular Biology and Evolution, 2004
Bilaterian animals are notably characterized by complex endocrine systems. The receptors for many steroids, retinoids, and other hormones belong to the superfamily of nuclear receptors, which are transcription factors regulating many aspects of development and homeostasis. Despite a diversity of regulatory mechanisms and physiological roles, nuclear receptors share a common protein organization. To obtain the broad picture of bilaterian nuclear hormone receptor evolution, we have characterized the complete set of nuclear receptor genes from nine animal genome sequences and analyzed it in a phylogenetic framework. In addition, expressed sequence tags from key lineages with no available genome sequence were also searched. This allows us to date the evolutionary events that led from an ancestral nuclear receptor gene, in an early metazoan, to present day diversity. We show that there were ;25 nuclear receptor genes in Urbilateria, the ancestor of bilaterians, at which point the fundamental diversity of the subfamily was already established. Surprisingly, differential gene loss played an important role in the evolution of different nuclear receptor sets in bilaterian lineages. The nuclear
Evolution of the nuclear receptor family
The EMBO Journal
Nuclear receptor genes represent a large family of genes encoding receptors for various hydrophobic ligands such as steroids, vitamin D, retinoic acid and thyroid hormones. This family also contains genes encoding putative receptors for unknown ligands. Nuclear receptor gene products are composed of several domains important for transcriptional activation, DNA binding (C domain), hormone binding and dinerization (E domain). It is not known whether these genes have evolved through gene duplication from a common ancestor or if their different domains came from different independent sources. To test these possibilities we have constructed and compared the phylogenetic trees derived from two different domains of 30 nuclear receptor genes. The tree built from the DNA binding C domain clearly shows a common progeny of all nuclear receptors, which can be grouped into three subfamilies: (i) thyroid hormone and retinoic acid receptors, (ii) orphan receptors and (iii) steroid honnone receptors. The tree constructed from the central part of the E domain which is implicated in transcriptional regulation and dimerization shows the same distribution in three subfamilies but two groups of receptors are in a different position from that in the C domain tree: (i) the Drosophila knirps family genes have acquired very different E domains during evolution, and (li) the vitamin D and ecdysone receptors, as well as the FTZ-F1 and the NGF1B genes, seem to have DNA binding and hormone binding domains belonging to different classes. These data suggest a complex evolutionary history for nuclear receptor genes in which gene duplication events and swapping between domains of different origins took place.
Evolutionary genomics of nuclear receptors: from 25 ancestral genes to derived endocrine
2014
Bilaterian animals are notably characterized by complex endocrine systems. The receptors for many steroids, retinoids, and other hormones belong to the superfamily of nuclear receptors, which are transcription factors regulating many aspects of development and homeostasis. Despite a diversity of regulatory mechanisms and physiological roles, nuclear receptors share a common protein organization. To obtain the broad picture of bilaterian nuclear hormone receptor evolution, we have characterized the complete set of nuclear receptor genes from nine animal genome sequences and analyzed it in a phylogenetic framework. In addition, expressed sequence tags from key lineages with no available genome sequence were also searched. This allows us to date the evolutionary events that led from an ancestral nuclear receptor gene, in an early metazoan, to present day diversity. We show that there were ;25 nuclear receptor genes in Urbilateria, the ancestor of bilaterians, at which point the fundamental diversity of the subfamily was already established. Surprisingly, differential gene loss played an important role in the evolution of different nuclear receptor sets in bilaterian lineages. The nuclear receptor distribution was also shaped by periods of gene duplication, essentially in vertebrates, as well as a lineage-specific duplication burst in nematodes. Our results imply that the genes for major receptors such as steroid receptors or thyroid hormone receptors were present in Urbilateria.
Ligand binding was acquired during evolution of nuclear receptors
Proceedings of the National Academy of Sciences, 1997
The nuclear receptor (NR) superfamily comprises, in addition to ligand-activated transcription factors, members for which no ligand has been identified to date. We demonstrate that orphan receptors are randomly distributed in the evolutionary tree and that there is no relationship between the position of a given liganded receptor in the tree and the chemical nature of its ligand. NRs are specific to metazoans, as revealed by a screen of NR-related sequences in early-and non-metazoan organisms. The analysis of the NR gene duplication pattern during the evolution of metazoans shows that the present NR diversity arose from two waves of gene duplications. Strikingly, our results suggest that the ancestral NR was an orphan receptor that acquired ligandbinding ability during subsequent evolution.
Evolutionary genomics of nuclear receptors: from 25 ancestral genes to derived endocrine systems
2000
Bilaterian animals are notably characterized by complex endocrine systems. The receptors for many steroids, retinoids, and other hormones, belong to the superfamily of nuclear receptors, which are transcription factors regulating many aspects of development and homeostasis. Despite a diversity of regulatory mechanisms and of physiological roles, nuclear receptors share a common protein organization. To obtain the broad picture of bilaterian nuclear hormone receptor evolution, we have characterized the complete set of nuclear receptor genes from nine animal genome sequences, and analyzed it in a phylogenetic framework. In addition, Expressed Sequence Tags from key lineages with no available genome sequence were also searched. This allows us to date the evolutionary events which led from an ancestral nuclear receptor gene, in an early metazoan, to present day diversity. We show that there were ca. 25 nuclear receptor genes in Urbilateria, the ancestor of bilaterians, at which point the fundamental diversity of the subfamily was already established.
Nuclear receptors are markers of animal genome evolution
Nuclear hormone receptors form one evolutionary related super-family of proteins, which mediate the interaction between hormones (or other ligands) and gene expression in animals. Early phylogenetic analyses showed two main periods of gene duplication which gave rise to present-day diversity in most animals: one at the origin of the family, and another specifically in vertebrates. Moreover this second period is composed itself by, probably, two rounds of duplication, as proposed by Susumu Ohno at the origin of vertebrates. There are indeed often two, three or four vertebrate orthologs of each invertebrate nuclear receptor, in accordance with this theory. The complete genome of Drosophila melanogaster contains 21 nuclear receptors, compared to 49 in the human genome. In addition, many nuclear receptors have more paralogs in the zebrafish than in mammals, and a genome duplication has been proposed at the origin of ray-finned fishes. Nuclear receptors are a very good model to investigate the dating and functional role of these duplications, since they are dispersed in the genome, allow robust phylogenetic reconstruction, and are functionnaly well characterized, with different adaptations for different paralogs. We illustrate this with examples from differents nuclear receptors and different groups of species.
PeerJ, 2017
Trichoplax adhaerens, the only known species of Placozoa is likely to be closely related to an early metazoan that preceded branching of Cnidaria and Bilateria. This animal species is surprisingly well adapted to free life in the World Ocean inhabiting tidal costal zones of oceans and seas with warm to moderate temperatures and shallow waters. The genome of T. adhaerens (sp. Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues. In the case of RXR, the sequence identity to human RXR alpha reaches 81% in the DNA binding domain and 70% in the ligand binding domain. We show that T. adhaerens RXR (TaRXR) binds 9-cis retinoic acid (9-cis-RA) with high affinity, as well as high specificity and that exposure of T. adhaerens to 9-cis-RA regulates the expression of the putative T. adhaerens orthologue of vertebrate L-malate-NADP + oxidoreductase (EC 1.1.1.40) which in vertebrates is regulated by a heterodimer of RXR and thyroid hormone receptor. Treatment by 9-cis-RA alters the relative expression profile of T. adhaerens nuclear receptors, suggesting the existence of natural ligands. Keeping with this, algal food composition has a profound effect on T. adhaerens growth and appearance. We show that nanomolar concentrations of 9-cis-RA interfere with T. adhaerens growth response to specific algal food and causes growth arrest. Our results uncover an endocrine-like network of nuclear receptors sensitive to 9-cis-RA in T. adhaerens and support the existence of a ligand-sensitive network of nuclear receptors at the base of metazoan evolution.