Evolutionary and Functional Analysis of Monoamine Oxidase C (MAO C): A Novel Member of the MAO Gene Family

Abstract

The monoamine oxidase (MAO) gene family encodes for enzymes that perform the oxidative deamination of monoamines, a process required to degrade norepinephrine, serotonin, dopamine, and other amines. While mammalian MAO enzymes, MAO A and MAO B, have been extensively studied, the molecular properties of the other family members are only partly uncovered. This study aims to explore the evolution of monoamine oxidases, emphasizing understanding the MAO gene repertoire among vertebrates. Our analyses show that the duplication that gave rise to MAO A and MAO B occurred in the ancestor of tetrapods, between 408 and 352 million years ago. Non-tetrapod jawed vertebrates possess the ancestral preduplicative condition of MAO A/B. Our results also identified a new family member, MAO C, in non-tetrapod jawed vertebrates. Thus, most jawed vertebrates possess a repertoire of two MAO genes, MAO A and MAO B in tetrapods and MAO A/B and MAO C in non-tetrapod jawed vertebrates, representing different MAO gene lineages. Jawless vertebrates possess the ancestral condition of a single copy gene, MAO A/B/C. Enzymatic assays conducted on the MAO recombinant enzymes of the Indo-Pacific tarpon show that both proteins, MAO A/B and MAO C, have enzymatic and molecular properties more similar to human MAO A, with the former featuring a strikingly higher activity rate when compared to all other MAO enzymes. Our analyses underscore the importance of scanning the tree of life for new gene lineages to understand phenotypic diversity and gain detailed insights into their function.