Insight into Evolution and Conservation Patterns of B1-Subfamily Members of GPCR

Abstract

The diverse, evolutionary architectures of proteins can be regarded as molecular fossils, tracing a historical path that marks important milestones across life. The B1-subfamily of GPCRs (G-protein-coupled receptors) are medically significant proteins that comprise 15 transmembrane receptor proteins in Homo sapiens. These proteins control the intracellular concentration of cyclic AMP as well as various vital processes in the body. However, little is known about the evolutionary correlation and conservational blueprint of this GPCR subfamily. We performed a comprehensive analysis to understand the evolutionary architecture among 13 members of the B1-subfamily. Multiple sequence alignment analysis exhibited six multiple sequence aligned blocks and five highly aligned blocks. Molecular phylogenetics indicated that CRHR1 and CRHR2 share a typical ancestral relationship and are siblings in 100% bootstrap replications with a total of 24 nodes observed in the cladogram. CRHR2 has the maximum number of extremely conserved amino acids followed by ADCYAP1R1. The longest continuous number sequence logos (74) were found between sequence location 349 and 423, and consequently, the maximum and minimum logo height recorded was 3.6 bits and 0.18 bits, respectively. Finally, to understand the model and pattern of evolutionary relatedness, the conservation blueprint, and the diversification among the members of a protein family, GPCR distribution from several species throughout the animal kingdom was analysed. Together, the study provides an evolutionary insight and offers a rapid method to explore the potential of depicting the evolutionary relationship, conservation blueprint, and diversification among the B1-subfamily of GPCRs using bioinformatics, algorithm analysis, and mathematical models.

New Insights into the Structure and Function of Class B1 GPCRs

“…Fifteen members of the class B1 family have been identified in humans, with high sequence homology across vertebrate species, including basal vertebrates such as hagfish and lamprey ( 8 ). Homologs of vertebrate class B1 GPCR genes are also found among invertebrate genomes, including in Caenorhabditis elegans and in Drosophila melanogaster , but the role of these and their relation to human B1 GPCR genes remains poorly understood ( 9 ).…”

Revealing Propolis Potential Activity on Inhibiting Estrogen Receptor and Heat Shock Protein 90 Overexpressed in Breast Cancer by Bioinformatics Approaches

“…These important roles are gained because the conserved region generally has crucial structural and functional protein activity. 74 Figures 6 and 7 showed that all important residues from both proteins were predicted to have a high conservation value.…”