A New Family of Diverse Skin Peptides from the Microhylid Frog Genus Phrynomantis.

Benoit Stijlemans,Steven Ballet,Shabnam Zaman,Frank Pasmans,Constantijn Raaymakers,An Martel,Charlotte Martin,Kim Roelants

doi:10.3390/molecules25040912

Benoit Stijlemans, Steven Ballet + Show 6 more

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https://doi.org/10.3390/molecules25040912

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Abstract

A wide range of frogs produce skin poisons composed of bioactive peptides for defence against pathogens, parasites and predators. While several frog families have been thoroughly screened for skin-secreted peptides, others, like the Microhylidae, have remained mostly unexplored. Previous studies of microhylids found no evidence of peptide secretion, suggesting that this defence adaptation was evolutionarily lost. We conducted transcriptome analyses of the skins of Phrynomantis bifasciatus and Phrynomantis microps, two African microhylid species long suspected to be poisonous. Our analyses reveal 17 evolutionary related transcripts that diversified from to those of cytolytic peptides found in other frog families. The 19 peptides predicted to be processed from these transcripts, named phrynomantins, show a striking structural diversity that is distinct from any previously identified frog skin peptide. Functional analyses of five phrynomantins confirm the loss of a cytolytic function and the absence of insecticidal or proinflammatory activity, suggesting that they represent an evolutionary transition to a new, yet unknown function. Our study shows that peptides have been retained in the defence poison of at least one microhylid lineage and encourages research on similarly understudied taxa to further elucidate the diversity and evolution of skin defence molecules.

Highlights

The amphibian skin is a delicate but sophisticated organ that is directly exposed to the challenges of the animal’s environment
Basic Local Alignment Search Tool (BLAST) searches against the same database as well as an in-house database of published amphibian secretory precursor proteins show that other highly expressed transcripts in Phrynomantis encode members of multiple protein families that are frequently encountered in frog skin secretions (Table 1)
As the Frog Skin Active Peptide’ (FSAP) superfamily constitutes a major component of skin secretions in other frog lineages, their finding in Phrynomantis is a first indication that peptide secretion has been evolutionary preserved in at least one microhylid lineage

Summary

Introduction

The amphibian skin is a delicate but sophisticated organ that is directly exposed to the challenges of the animal’s environment. Molecules 2020, 25, 912 genera in the families Phyllomedusidae (Agalychnis and Phyllomedusa), Pelodryadidae (Litoria) and Ranidae (Rana, Lithobates and Odorrana) have been thoroughly explored for the presence of therapeutically promising peptides [11,12,13]. These peptides often display different bioactivities and range from antimicrobial or antioxidant agents, to hormone analogues that can cause sickness, hypotension or inflammation [1,2]. These precursor proteins have been classified in the ‘Frog Skin Active Peptide’ (FSAP)

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