Conserved patterns classify human olfactory receptor families in functionally associated manner

Abstract

The odorant receptor (OR) is a main character in making olfactory sensory neurons (OSNs) activated by interacting with structurally diverse odorant molecules. Mammalian genomes are well established, and highly conserved regions within ORs have been identified. Numerous studies have focused on specific conserved amino acid motifs of ORs to examine their functional roles, which underlines their contribution to receptor functions. There are several variable regions among conserved motifs, and we found the patterns of variations within consensus amino acid sequences of ORs. Based on our hypothesis that the related functions can be inferred from the pattern of variations in the conserved motifs of ORs. we performed hierarchical clustering of intact human OR proteins according to the concordance rate for selected conserved motifs. Human ORs were divided into two large groups, and classified into 6 sub-clusters according to the conserved patterns. We observed that the standard for dividing human ORs into two large groups is M (methionine) of PMLNPL/FIY, and verified the role of this region with selected representative OR models by conducting heterologous in vitro assay. This study proposed a new index for OR functions by presenting a conserved motif as a criterion for the classification of human OR families that were not fully explained by existing classifications.