Parathyroid hormone gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii)

AbstractWe report the analysis of activation of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates by corticosteroids and progesterone. Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes. Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Both elephant shark MR and human MR are expressed in the brain, heart, ovary, testis and other non-epithelial tissues, indicating that MR expression in diverse tissues evolved in the common ancestor of jawed vertebrates. Our data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.

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The elephant shark methylome reveals conservation of epigenetic regulation across jawed vertebrates

F1000Research ◽

10.12688/f1000research.11281.1 ◽

2017 ◽

Vol 6 ◽

pp. 526 ◽

Cited By ~ 11

Author(s):

Julian R. Peat ◽

Oscar Ortega-Recalde ◽

Olga Kardailsky ◽

Timothy A. Hore

Keyword(s):

Epigenetic Modification ◽

Regulatory Elements ◽

Cartilaginous Fish ◽

Critical System ◽

Modification System ◽

Elephant Shark ◽

Transcription Start Sites ◽

Regulatory Architecture ◽

Transposon Activity ◽

And Function

Background: Methylation of CG dinucleotides constitutes a critical system of epigenetic memory in bony vertebrates, where it modulates gene expression and suppresses transposon activity. The genomes of studied vertebrates are pervasively hypermethylated, with the exception of regulatory elements such as transcription start sites (TSSs), where the presence of methylation is associated with gene silencing. This system is not found in the sparsely methylated genomes of invertebrates, and establishing how it arose during early vertebrate evolution is impeded by a paucity of epigenetic data from basal vertebrates. Methods: We perform whole-genome bisulfite sequencing to generate the first genome-wide methylation profiles of a cartilaginous fish, the elephant shark Callorhinchus milii. Employing these to determine the elephant shark methylome structure and its relationship with expression, we compare this with higher vertebrates and an invertebrate chordate using published methylation and transcriptome data. Results: Like higher vertebrates, the majority of elephant shark CG sites are highly methylated, and methylation is abundant across the genome rather than patterned in the mosaic configuration of invertebrates. This global hypermethylation includes transposable elements and the bodies of genes at all expression levels. Significantly, we document an inverse relationship between TSS methylation and expression in the elephant shark, supporting the presence of the repressive regulatory architecture shared by higher vertebrates. Conclusions: Our demonstration that methylation patterns in a cartilaginous fish are characteristic of higher vertebrates imply the conservation of this epigenetic modification system across jawed vertebrates separated by 465 million years of evolution. In addition, these findings position the elephant shark as a valuable model to explore the evolutionary history and function of vertebrate methylation.

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Transcriptional Activation of Elephant Shark Mineralocorticoid Receptor by Corticosteroids, Progesterone and Spironolactone

10.20944/preprints201903.0001.v1 ◽

2019 ◽

Author(s):

Yoshinao Katsu ◽

Satomi Kohno ◽

Kaori Oka ◽

Xiaozhi Lin ◽

Sumika Otake ◽

...

Keyword(s):

Sequence Analysis ◽

Human Brain ◽

Transcriptional Activation ◽

Mineralocorticoid Receptor ◽

Cartilaginous Fish ◽

Full Length ◽

Rna Sequence ◽

Elephant Shark ◽

Terrestrial Vertebrates ◽

Cartilaginous Fishes

We report the analysis of activation by corticosteroids and progesterone of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates.  Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids.  However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes.  Because progesterone is a precursor for corticosteroids that activate elephant shark MR, we propose that progesterone was an ancestral ligand for elephant shark MR.  Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR.  Comparison of RNA-sequence analysis of elephant shark MR with that of human MR suggests that MR expression in the human brain, heart, ovary, testis and other non-epithelial tissues evolved in cartilaginous fishes.  Together, these data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.

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Regulation by Progestins, Corticosteroids and RU486 of Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective

10.1101/2021.01.20.427507 ◽

2021 ◽

Author(s):

Xiaozhi Lin ◽

Wataru Takagi ◽

Susumu Hyodo ◽

Shigeho Ijiri ◽

Yoshinao Katsu ◽

...

Keyword(s):

Progesterone Receptor ◽

Progesterone Receptors ◽

Cartilaginous Fish ◽

Evolutionary Perspective ◽

Elephant Shark ◽

Hydroxy Progesterone

AbstractWe investigated progestin and corticosteroid activation of the progesterone receptor (PR) from elephant shark (Callorhinchus milii), a cartilaginous fish belonging to the oldest group of jawed vertebrates. Comparison with human PR experiments provides insights into the evolution of steroid activation of human PR. At 1 nM steroid, elephant shark PR is activated by progesterone, 17-hydroxy-progesterone, 20β-hydroxy-progesterone, 11-deoxycorticosterone (21-hydroxyprogesterone) and 11-deoxycortisol. At 1 nM steroid, human PR is activated only by progesterone and11-deoxycorticosterone indicating increased specificity for progestins and corticosteroids during the evolution of human PR. RU486, an important clinical antagonist of human PR, did not inhibit progesterone activation of elephant shark PR. Cys-528 in elephant shark PR corresponds to Gly-722 in human PR, which is essential for RU486 inhibition of human PR. Confirming the importance of this site on elephant shark PR, RU486 inhibited progesterone activation of the Cys528Gly mutant PR. There also was a decline in activation of elephant shark Cys528Gly PR by 11-deoxycortisol, 17-hydroxy-progesterone and 20β-hydroxy-progesterone and an increase in activation of human Gly722Cys PR by 11-deoxycortisol and decreased activation by corticosterone. One or more of these changes may have selected for the mutation corresponding to human glycine-722 PR that first evolved in platypus PR, a basal mammal.

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Runx Family Genes in a Cartilaginous Fish, the Elephant Shark (Callorhinchus milii)

PLoS ONE ◽

10.1371/journal.pone.0093816 ◽

2014 ◽

Vol 9 (4) ◽

pp. e93816 ◽

Cited By ~ 4

Author(s):

Giselle Sek Suan Nah ◽

Zhi Wei Lim ◽

Boon-Hui Tay ◽

Motomi Osato ◽

Byrappa Venkatesh

Keyword(s):

Cartilaginous Fish ◽

Elephant Shark

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Transcriptional Activation of Elephant Shark Mineralocorticoid Receptor by Corticosteroids, Progesterone and Spironolactone

10.32942/osf.io/u56ar ◽

2019 ◽

Cited By ~ 1

Author(s):

Yoshinao Katsu ◽

Satomi Kohno ◽

Kaori Oka ◽

Xiaozhi Lin ◽

Sumika Otake ◽

...

Keyword(s):

Sequence Analysis ◽

Human Brain ◽

Transcriptional Activation ◽

Mineralocorticoid Receptor ◽

Cartilaginous Fish ◽

Full Length ◽

Rna Sequence ◽

Elephant Shark ◽

Terrestrial Vertebrates ◽

Cartilaginous Fishes

We report the analysis of activation by corticosteroids and progesterone of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes. Because progesterone is a precursor for corticosteroids that activate elephant shark MR, we propose that progesterone was an ancestral ligand for elephant shark MR. Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Comparison of RNA-sequence analysis of elephant shark MR with that of human MR suggests that MR expression in the human brain, heart, ovary, testis and other non-epithelial tissues evolved in cartilaginous fishes. Together, these data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.

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Identification of an MRAP-Independent Melanocortin-2 Receptor: Functional Expression of the Cartilaginous Fish, Callorhinchus milii, Melanocortin-2 Receptor in CHO Cells

Endocrinology ◽

10.1210/en.2012-1482 ◽

2012 ◽

Vol 153 (10) ◽

pp. 4757-4765 ◽

Cited By ~ 26

Author(s):

Christina L. Reinick ◽

Liang Liang ◽

Joseph K. Angleson ◽

Robert M. Dores

Keyword(s):

Cho Cells ◽

Phylogenetic Analyses ◽

Chinese Hamster ◽

Functional Expression ◽

Cartilaginous Fish ◽

Melanocortin Receptor ◽

Accessory Protein ◽

Dependent Manner ◽

Elephant Shark ◽

Ligand Selectivity

Abstract Phylogenetic analyses indicate that the genome of the cartilaginous fish, Callorhynchus milii (elephant shark), encodes a melanocortin-2 receptor (MC2R) ortholog. Expression of the elephant shark mc2r cDNA in Chinese hamster ovary (CHO) cells revealed that trafficking to the plasma membrane and functional activation of the receptor do not require coexpression with an exogenous melanocortin receptor-2 accessory protein (mrap) cDNA. Ligand selectivity studies indicated that elephant shark MC2R-transfected CHO cells produced cAMP in a dose-dependent manner when stimulated with either human ACTH (1–24) or [Nle4, d-Phe7]-MSH. Furthermore, the order of ligand selectivity when elephant shark MC2R-transfected CHO cells were stimulated with cartilaginous fish melanocortins was as follows: ACTH (1–25) = γ-MSH = δ-MSH > αMSH = β-MSH. Elephant shark MC2R is the first vertebrate MC2R ortholog to be analyzed that does not require melanocortin receptor-2 accessory protein 1 for functional activation. In addition, elephant MC2R is currently the only MC2R ortholog that can be activated by either ACTH- or MSH-sized ligands. Hence, it would appear that MC2R dependence on melanocortin receptor-2 accessory protein 1 for functional activation and the exclusive selectivity of this melanocortin receptor for ACTH are features that emerged after the divergence of the ancestral cartilaginous fishes and the ancestral bony fishes more than 400 million years ago.

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