Mineralocorticoid receptors: evolutionary and pathophysiological considerations

Kassahn, Karin S., Ragan, Mark A. and Funder, John W. (2011) Mineralocorticoid receptors: evolutionary and pathophysiological considerations. Endocrinology, 152 5: 1883-1890. doi:10.1210/en.2010-1444

Author Kassahn, Karin S.
Ragan, Mark A.
Funder, John W.
Title Mineralocorticoid receptors: evolutionary and pathophysiological considerations
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2011-05-01
Sub-type Article (original research)
DOI 10.1210/en.2010-1444
Volume 152
Issue 5
Start page 1883
End page 1890
Total pages 8
Place of publication United States
Publisher The Endocrine Society
Collection year 2012
Language eng
Abstract Mineralocorticoid receptors (MR), glucocorticoid receptors (GR), progesterone receptors (PR), and androgen receptors (AR) comprise a closely related subfamily within the human 49-mem-ber nuclear receptor family. These receptors and their cognate ligands play major roles in homeostasis, reproduction, growth, and development, despite which their evolution and diversification remains incompletely understood. Several conflicting models have been advanced for the evolution of this subfamily. We have thus undertaken Bayesian and maximum likelihood phylogeneticanalyses of thissubfamily. The Bayesian consensus and maximum likelihood trees support a basal position for MR, with the PR and AR forming a sister clade. We next performed analyses using topological constraints to directly contrast the likelihood of seven phylogenetic models. In these analyses, three models have similar support: one proposes two sister clades (MR and GR, PR and AR); the other two propose a different subfamily member (MR or GR) to be the first to have diverged. Ancestral state reconstructions at sites critical for physiological function show that the S810L mutation in the MR, which results in the MR being similar to estrogen receptors and the more distantly related retinoic acid receptor-α is likely to reflect the ancestral receptor sequence before the divergence of this subfamily and provides further support for MR having been the first of the subfamily to diverge. Finally, we drew on pathophysiological comparisons to help to distinguish the different models. On the basis of our phylogeneticanalyses and pathophysiological considerations, we propose that the MR was the first to diverge from the ancestral gene lineage from which this subfamily derived.
Keyword Whole-genome duplication
Nuclear receptor
Protein sequences
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 04 May 2011, 18:04:24 EST by Dr Karin Kassahn on behalf of Institute for Molecular Bioscience