In silico investigation of intronless Rhodopsin-like G-protein coupled receptors (GPCR) in the human genome: features and classification.

The G-protein coupled receptors (GPCRs) form a large protein family in the human genome that have been widely studied and classified into classes and phylogenetic subfamilies. However, there still exist orphan GPCRs that are not classified in any of the known subfamilies and new bioinformatics approaches are still needed to address this issue. One of the interesting features of GPCRs is that a large proportion of these proteins are encoded by intronless genes. In this work, we are interested in the study of Rhodpsin-like GPCRs proteins encoded by this kind of genes. After a manual validation of their gene structure, we studied some of their properties including the number of exons, chromosomal location and protein length. The same trend was found for intronless GPCRs as compared to total GPCRs, particularly the uneven chromosomal distribution with a large number (one third) of GPCRs on chromosomes 1 and 11. The proportion of intronless GPCRs among all Rhdopsin-like GPCRs was estimated to about 26% which is significantly less than previously reported. Significant differences in protein length were found between subfamilies. We then used composition properties of DNA and protein sequences to classify intronless Rhodopsin-like GPCRs. Principal component analysis was used to identify key variable and then a discriminant analysis was used to compute discriminant functions that best separates the phylogenetic subfamilies. We found that the most important features to separates the groups is the proportion of aromatic amino acids in protein sequence and the contrast between (A+T) versus (G+C) in coding sequence. These functions are finally used to classify fourteen putative or unclassified GPCRs.