Transcriptomic Signatures of Experimental Alkaloid Consumption in a Poison Frog

Eugenia Sanchez,Miguel Vences,Jose H Grau,Ariel Rodríguez,Stefan Schulz,Katharina C Wollenberg Valero,Stefan Lötters,Ralph A Saporito,Eva Ringler,Sven Künzel

doi:10.3390/genes10100733

Abstract

In the anuran family Dendrobatidae, aposematic species obtain their toxic or unpalatable alkaloids from dietary sources, a process known as sequestering. To understand how toxicity evolved in this family, it is paramount to elucidate the pathways of alkaloid processing (absorption, metabolism, and sequestering). Here, we used an exploratory skin gene expression experiment in which captive-bred dendrobatids were fed alkaloids. Most of these experiments were performed with Dendrobates tinctorius, but some trials were performed with D. auratus, D. leucomelas and Allobates femoralis to explore whether other dendrobatids would show similar patterns of gene expression. We found a consistent pattern of up-regulation of genes related to muscle and mitochondrial processes, probably due to the lack of mutations related to alkaloid resistance in these species. Considering conserved pathways of drug metabolism in vertebrates, we hypothesize alkaloid degradation is a physiological mechanism of resistance, which was evidenced by a strong upregulation of the immune system in D. tinctorius, and of complement C2 across the four species sampled. Probably related to this strong immune response, we found several skin keratins downregulated, which might be linked to a reduction of the cornified layer of the epidermis. Although not conclusive, our results offer candidate genes and testable hypotheses to elucidate alkaloid processing in poison frogs.

Highlights

Alkaloids are unpalatable or toxic substances, and have been documented in five families of anurans [1,2,3,4,5]
From a biochemical point of view, alkaloid processing in poison frogs is remarkable because they are sequestered without modifying their molecular structure in most cases [5]
Alkaloids have been found in several tissues of poison frogs [22], they are mainly stored in the skin, purportedly in the granules of the granular glands [23,24,25]; the skin is a target organ in which to study alkaloid internalization and storage

Summary

Introduction

Alkaloids are unpalatable or toxic substances, and have been documented in five families of anurans [1,2,3,4,5] In one of these families, Dendrobatidae, the ability to uptake and store alkaloids from the diet, known as sequestering, evolved independently at least four times [6,7,8]. Alkaloids might either circulate freely, as part of lipoproteins, or bind to carrier protein(s). Before they reach the tissue of storage, they could (or not) be metabolized. Alkaloids have been found in several tissues of poison frogs [22], they are mainly stored in the skin, purportedly in the granules of the granular glands [23,24,25]; the skin is a target organ in which to study alkaloid internalization and storage

Methods

Results

Conclusion