Cartilaginous Fishes Provide Insights into the Origin, Diversification, and Sexually Dimorphic Expression of Vertebrate Estrogen Receptor Genes

  title={Cartilaginous Fishes Provide Insights into the Origin, Diversification, and Sexually Dimorphic Expression of Vertebrate Estrogen Receptor Genes},
  author={Grant L Filowitz and Rajendhran Rajakumar and Katherine L O’Shaughnessy and Martin J. Cohn},
  journal={Molecular Biology and Evolution},
Vertebrate estrogen receptors (ERs) perform numerous cell signaling and transcriptional regulatory functions. ERɑ (Esr1) and ERβ (Esr2) likely evolved from an ancestral receptor that duplicated and diverged at the protein and cis-regulatory levels, but the evolutionary history of ERs, including the timing of proposed duplications, remains unresolved. Here we report on identification of two distinct ERs in cartilaginous fishes and demonstrate their orthology to ERα and ERβ. Phylogenetic analyses… Expand
4 Citations
Cartilaginous fishes offer unique insights into the evolution of the nuclear receptor gene repertoire in gnathostomes.
It is shown that cartilaginous fish retain an archetypal NR gene repertoire, similar to that of mammals and coincident with the two rounds of whole genome duplication that occurred in the gnathostome ancestor. Expand
Steroid receptors and vertebrate evolution
  • M. Baker
  • Biology, Medicine
  • Molecular and Cellular Endocrinology
  • 2019
Results from sequence analyses of genomes from bacteria, yeast, plants, invertebrates and vertebrates indicate that receptors for adrenal steroids, and sex steroids, also are young, with an estrogen receptor and a 3-ketosteroid receptor first appearing in basal chordates (cephalochordates: amphioxus). Expand
Steroid Receptors and Vertebrate Evolution
The presence of steroid receptors in vertebrates, in which these steroid receptors act as master switches to regulate differentiation, development, reproduction, immune responses, electrolyte homeostasis and stress responses, argues for an important role for steroid receptor in the evolutionary success of vertebrates. Expand
Sex steroids as mediators of phenotypic integration, genetic correlations, and evolutionary transitions
  • R. Cox
  • Biology, Medicine
  • Molecular and Cellular Endocrinology
  • 2020
The rapidly increasing availability of genomic and transcriptomic data from non-model organisms places evolutionary endocrinologist in an excellent position to address the hormonal regulation of the key evolutionary interface between genes and phenotypes. Expand


Molecular cloning, characterization, and evolutionary analysis of estrogen receptors from phylogenetically ancient fish.
Sequence analyses indicate that lungfish, sturgeon, and gar have two ESRs, ESR1 (ERalpha) and ESR2 (ERbeta), as previously reported for other vertebrate species, but a second type of E SR2 was not found as has been reported in a number of teleost fishes. Expand
A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription.
To understand the evolution of vertebrate ERs and to investigate how estrogen acts in a jawless vertebrate, degenerate primer sets and PCR are used to isolate DNA fragments encoding two distinct ER subtypes, Esr1a and EsR1b from the Japanese lamprey. Expand
Elephant shark genome provides unique insights into gnathostome evolution
The whole-genome analysis of a cartilaginous fish, the elephant shark (Callorhinchus milii), finds that the C. milii genome is the slowest evolving of all known vertebrates, and features extensive synteny conservation with tetrapod genomes, making it a good model for comparative analyses of gnathostome genomes. Expand
Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions
  • J. W. Thornton
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2001
A model of ligand exploitation is supported in which the terminal ligand in a biosynthetic pathway is the first for which a receptor evolves; selection for this hormone also selects for the synthesis of intermediates despite the absence of receptors, and duplicated receptors then evolve affinity for these substances. Expand
Molecular cloning and characterization of hagfish estrogen receptors
Cloned and characterized cDNAs from the inshore hagfish, Eptatretus burgeri, to better understand the molecular evolution of ERs, demonstrating that the hag fish has two functional ER subtypes. Expand
Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors: toward a better understanding of estrogen receptor evolution.
Artificial-intelligence-based software was used to construct 12 motifs specific to the estrogen-binding domain of ERalpha and ERbeta in land vertebrates and teleosts, which depicted residues in human ERalpha that interact with estradiol, which revealed significant differences between amphioxus ER and vertebrate ERs in the steroid- binding domain. Expand
Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors.
The effects of natural estrogens, ethinylestradiol, and DDT and its metabolites on the transactivation of the four amphibian species and Xenopus tropicalis ERs are analyzed and found that there were species-specific differences in the sensitivity of these ERs to hormones and environmental chemicals. Expand
Analysis of EphA4 in the lesser spotted catshark identifies a primitive gnathostome expression pattern and reveals co-option during evolution of shark-specific morphology
A dynamic pattern of EphA4 expression occurs during shark fin development, suggesting an early role in outgrowth and patterning of the fin buds and a later role in tissue differentiation. Expand
Cloning and functional characterization of Chondrichthyes, cloudy catshark, Scyliorhinus torazame and whale shark, Rhincodon typus estrogen receptors.
To understand the molecular mechanisms of estrogen actions and to evaluate estrogen receptor-ligand interactions in Elasmobranchii, a single estrogen receptor (ESR) from two shark species is cloned and an ERE-luciferase reporter assay system is used to characterize the interaction of these receptors with steroidal and other environmental estrogens. Expand
Origin of the response to adrenal and sex steroids: Roles of promiscuity and co-evolution of enzymes and steroid receptors
Together, this suite of receptors and enzymes through their roles in transcriptional regulation of reproduction, development, homeostasis and the response to stress contributed to the evolutionary diversification of vertebrates. Expand