Genomic organization of the expanded human OPRM1 locus is highly similar to the organization of the mouse OPRM1 locus. However, alternative splicing events within this locus display some substantial differences between human and mouse, and thus findings from rodent studies should be considered with caution when applied to the function of human opioid receptor. Specifically, our RT–PCR and 5′RACE data suggest that exon 13 containing OPRM1 mRNA variants in human and mouse are highly divergent (Fig. 2A–C; Supplementary Material, Fig. S5). New tissue-specific alternative splice isoforms increase functional diversity of the gene and create additional options for regulation, as demonstrated by the strong effect of SNP rs563649 on pain sensitivity (64). Importantly, location of this functional SNP in a region of variable inter-species conservation shows that biological function does not always correlate with sequence conservation.
