EXAMINING PHYLOGENETIC HISTORY OF THE EXTRACELLULAR CALCIUM-SENSING RECEPTOR: A KEY SENSOR IN CALCIUM HOMEOSTATIC SYSTEMS
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1
University at Buffalo, Department of Biological Sciences, United States
Ionic calcium (Ca2+) supports essential physiological functions in animals and, consequently, its concentration is homeostatically regulated within narrow bounds. The extracellular calcium-sensing receptor (CaSR) is a Family C G protein-coupled receptor (GPCR) that acts as a Ca2+ sensor, and as a nutrient sensor and perhaps in fishes as a salinity detector. Based on cDNA sequencing and genome database mining efforts, CaSRs are restricted to the chordate-vertebrate lineage. Using a data set comprising nucleotide and deduced protein sequences of vertebrate CaSRs, non-vertebrate chordate CaSR-like molecules and related Family C GPCRs, evolutionary relationships were inferred through phylogenetic tree estimation. Using statistical evaluation of non-synonymous (amino acid residue-altering; dN) versus synonymous (silent; dS) codon changes, differences in evolutionary selection among phylogenetic tree branches were demonstrated. Generally, within the major vertebrate clades there is strong evidence from this branch analysis for purifying selection during CaSR evolution from ancestral forms. But, notably, there is evidence of adaptive selection at the roots of the cartilaginous fish, bony fish, and tetrapod clades. This adaptive, or diversifying, evolutionary selection is interpreted in the context of skeletal biology (cartilaginous vs. mineralized bony skeleton) and natural history (aquatic vs. terrestrial lifestyles relative to the availability of environmental Ca2+). Homology modeling of three-dimensional protein structures and evolutionary trace (ET) analysis were applied to map functionally-important, conserved amino acid residues to the receptor’s molecular structure. ET analysis showed strong conservation among all vertebrates of amino acid residues at predicted Ca2+-binding sites in the receptor’s extracellular domain. Site analysis of dN/dS ratios revealed relaxation from purifying selection at some codon positions, suggesting different functional roles among clades.
Keywords:
calcium homeostasis,
calcium-sensing receptor,
evolutionary selection,
osmoregulation,
skeletal biology,
Vertebrates
Conference:
NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology, Ann Arbor, United States, 13 Jul - 16 Jul, 2011.
Presentation Type:
Poster
Topic:
Ion and water balance
Citation:
Herberger
A and
Loretz
CA
(2011). EXAMINING PHYLOGENETIC HISTORY OF THE EXTRACELLULAR CALCIUM-SENSING RECEPTOR: A KEY SENSOR IN CALCIUM HOMEOSTATIC SYSTEMS.
Front. Endocrinol.
Conference Abstract:
NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology.
doi: 10.3389/conf.fendo.2011.04.00025
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Received:
08 Jul 2011;
Published Online:
09 Aug 2011.
*
Correspondence:
Miss. Amanda Herberger, University at Buffalo, Department of Biological Sciences, Buffalo, New York, 14260-1300, United States, alh32@buffalo.edu