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Evolutionary relationships among G protein-coupled receptors using a clustered database approach
AAPS Pharmsci
|December 14, 2001
Summary
This study reevaluates the evolutionary relationships of Guanine nucleotide-binding protein-coupled receptors (GPCRs) using an expanded database and advanced sequence alignment. It reveals significant evolutionary links between diverse GPCR families, refining our understanding of their ancestry.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Bioinformatics
Background:
- Guanine nucleotide-binding protein-coupled receptors (GPCRs) are large, diverse gene families with a conserved 7-transmembrane segment structure.
- Minimal sequence similarity exists among distant GPCRs, complicating evolutionary relationship studies.
Purpose of the Study:
- To reevaluate the evolutionary relationships among disparate GPCR families using an increased number of cloned GPCRs.
- To establish a refined view of GPCR ancestry and facilitate database annotation.
Main Methods:
- Utilized an expanded database of approximately 1700 GPCRs from NCBI.
- Employed iterative BLAST searches and position-specific matrices for optimized sequence comparisons.
- Included unrelated membrane proteins as controls and divided sequences into 34 clusters.
Main Results:
- Achieved significant alignments between distant GPCR families, including biogenic amine/peptide, VIP/secretin, cAMP, fungal pheromone, latrophilin, frizzled, smoothened, metabotropic glutamate, and fungal glucose receptors.
- Failed to support homology between recognized GPCR clades and p40, pm1 (putative GPCRs), or bacteriorhodopsins.
- Provided a refined view of GPCR ancestry.
Conclusions:
- The study refines the understanding of GPCR evolutionary history by identifying significant alignments across diverse families.
- The findings aid in database annotation and the classification of orphan receptors.
- Establishes a reference database for GPCR research.