A "Neural" Enzyme in Nonbilaterian Animals and Algae: Preneural Origins for Peptidylglycine  -Amidating Monooxygenase

Abstract

Secreted peptides, produced by enzymatic processing of larger precursor molecules, are found throughout the animal kingdom and play important regulatory roles as neurotransmitters and hormones. Many require a carboxy-terminal modification, involving the conversion of a glycine residue into an a-amide, for their biological activity. Two sequential enzymatic activities catalyze this conversion: a monooxygenase (peptidylglycine a-hydroxylating monooxygenase or PHM) and an amidating lyase (peptidyl-a-hydroxyglycine a-amidating lyase or PAL). In vertebrates, these activities reside in a single polypeptide known as peptidylglycine a-amidating monooxygenase (PAM), which has been extensively studied in the context of neuropeptide modification. Bifunctional PAMs have been reported from some invertebrates, but the phylogenetic distribution of PAMs and their evolutionary relationship to PALs and PHMs is unclear. Here, we report sequence and expression data for two PAMs from the coral Acropora millepora (Anthozoa, Cnidaria), as well as providing a comprehensive survey of the available sequence data from other organisms. These analyses indicate that bifunctional PAMs predate the origins of the nervous and endocrine systems, consistent with the idea that within the Metazoa their ancestral function may have been to amidate epitheliopeptides. More surprisingly, the phylogenomic survey also revealed the presence of PAMs in green algae (but not in higher plants or fungi), implying that the bifunctional enzyme either predates the plant/animal divergence and has subsequently been lost in a number of lineages or perhaps that convergent evolution or lateral gene transfer has occurred. This finding is consistent with recent discoveries that other molecules once thought of as ''neural'' predate nervous systems.

Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

“…The PAM-like sequence previously predicted for Chlamydomonas lacked key residues in the PAL domain (Attenborough et al, 2012). Our analysis of sequenced Chlamydomonas expressed sequence tags (ESTs) and the subsequent release of an improved gene model revealed an additional exon, resulting in a domain organization for Cre03.g152850 (hereafter referred to as CrPAM) that is very similar to the mammalian PAM2 isoform (Fig.…”

“…The Chlamydomonas genome encodes an active prohormone-processing enzyme A previous phylogenetic study identified PAM-like genes in several green algal genomes including Chlamydomonas reinhardtii, Volvox carteri and Ostreococcus tauri (Attenborough et al, 2012). We report here the characterization of an active peptideamidating monooxygenase in Chlamydomonas (Cre03.g152850).…”

“…1B). Attenborough et al (2012) attributed their identification of organisms with genes encoding bifunctional PAM, monofunctional PHM and monofunctional PAL (as in D. melanogaster and C. elegans) to an early gene duplication. We revisited the phylogenetic distribution and found a striking correlation between the presence of cilia and bifunctional PAM or monofunctional PHM and PAL (Fig.…”

“…The identification of PAM-like genes in ciliated green algal genomes and in Amphimedon, the simplest animal lacking a nervous system, suggests that it was present in the last eukaryotic common ancestor (Attenborough et al, 2012). Like PAM, amidated peptides have not been found in yeast or higher plants (Jekely, 2013).…”

Peptide-gated ion channels and the simple nervous system of Hydra

“…In contrast to animals from other taxa, pNPs have so far not been found in the sponge Amphimedon queenslandica (Jékely, 2013), indicating that Porifera do not use peptides for paracrine communication. An amidating enzyme involved in pNP maturation, however, has been predicted in A. queenslandica (Attenborough et al, 2012), hinting at the possible presence of pNPs in sponges.…”