Molecular Evolution Of The Proopiomelanocortin System In Barn Owl Species

Examination of genetic polymorphisms in outbred wild-living species provides insights into the evolution of complex systems. In higher vertebrates, the proopiomelanocortin (POMC) precursor gives rise to alpha-, beta-, and gamma-melanocyte-stimulating hormones (MSH), which are involved in numerous physiological aspects. Genetic defects in POMC are linked to metabolic disorders in humans and animals. In the present study, we undertook an evolutionary genetic approach complemented with biochemistry to investigate the functional consequences of genetic polymorphisms in the POMC system of free-living outbred barn owl species (family Tytonidae) at the molecular level. Our phylogenetic studies revealed a striking correlation between a loss-of-function H9P mutation in the beta-MSH receptor-binding motif and an extension of a poly-serine stretch in gamma 3-MSH to >= 7 residues that arose in the barn owl group 6-8 MYA ago. We found that extension of the poly-serine stretches in the gamma-MSH locus affects POMC precursor processing, increasing gamma 3-MSH production at the expense of gamma 2-MSH and resulting in an overall reduction of gamma-MSH signaling, which may be part of a negative feedback mechanism. Extension of the gamma 3-MSH poly-serine stretches >= 7 further markedly increases peptide hormone stability in plasma, which is conserved in humans, and is likely relevant to its endocrine function. In sum, our phylogenetic analysis of POMC in wild living owls uncovered a H9P beta-MSH mutation subsequent to serine extension in gamma 3-MSH to 7 residues, which was then followed by further serine extension. The linked MSH mutations highlight the genetic plasticity enabled by the modular design of the POMC gene.