Tiny and Toxic

Eleutherodactylus iberia
In 1998, John W. Daly at the National Institutes of Health noted that amphibian skin contains a wide range of biologically active molecules and that in three decades (since 1968) more than 400 alkaloids in more than 20 structural classes have been detected. But perhaps most surprising, the alkaloids in amphibian skins were not made by the amphibians' cells, instead they were molecules hijacked from the arthropods the amphibians ate. Many of these molecules are used as defense against micro-organisms and predators. Other amphibian skin molecules are biosynthesized by the animal's own cells. But the alkaloids particularly those that are lipid soluble are made in the arthropod prey or possibly by symbiotic micro-organisms and stored in the amphibian's skin glands. Twelve years after Daly's paper more than 800 molecules have been identified.

But not all amphibians can take molecules from their prey and use them for their own defense. Perhaps the Neotropical poison-dart frogs (Dendrobatidae) are best known for this ability. Poison dart frogs kept in captivity and feed a diet a fruit flies are no longer poisonous. But there are other anurans that do this: the South American Red bellied Toads (genus Melanophryniscus, family Bufonidae); one genus of Madagascan Golden Frogs (Mantella, family Mantellidae); and one genus of Australian Toadlets (Pseudophryne, family Myobatrachidae). Minor quantities of alkaloids have also been found in the Asian genus Limnonectes (family Dicroglossidae) but it is unknown if they are also getting the alkaloid molecules from their food. Thus, the frogs that do sequester alkaloids from their prey are un-related, but they all tend to have aposematic coloration that signals predators that they are toxic.

Now, Ariel Rodriguez and colleagues (2010) report a 5th lineage of frogs that obtain defensive molecules from their prey, the minute Cuban, Eleutherodactylus iberia and Eleutherodactylus orientalis, (family Eleutherodactylidae). During recent fieldwork, the odor of dissected specimens reminded the authors of the alkaloid-containing dendrobatid and mantellid species. Further investigation provided conclusive evidence that these aposematic frogs contain lipid soluble alkaloids of the same compound classes previously reported in other alkaloid-containing frog lineages. The authors found six pumiliotoxins and two indolizidines in E. iberia but cannot confirm that alkaloid sequestering is characteristic for all populations of E. Iberia. And they are unsure whether it regularly occurs in E. orientalis and other related species of the E. limbatus group without extensive additional effort. However, the discovery that at least some of these frogs sequester lipid-soluble alkaloids may contribute to the understanding of the evolutionary pathway to alkaloid-sequestration and aposematism in amphibians. Examination of stomach contents indicated an abundance of oribatid mites, a group of arthropods known to contain one of the pumiliotoxins detected in E. iberia. This suggests that miniaturization and specialization to small prey may have favored the acquisition of dietary skin alkaloids in these amphibians. 

Of interest is the discovery that oribatid mites are a common prey for miniaturized frogs including the miniature Eleutherodactylus examined in this study. The two alkaloids of E. iberia have previously been detected in arthropods (mites and ants).  Additional evidence for the importance of miniaturization came from the phylogenetic position of the poorly known Wakea madinika, a dwarf frog from Madagascar, as the sister group of the alkaloid-containing genus Mantella, which might indicate that the Mantella ancestor was also miniaturized. The miniature Cuban Eleutherodactylus are largely diurnal, and aposematic in coloration. Other species in the same clade have a much less contrasted coloration and this group of frogs may be useful in understanding  how diet, miniaturization, the ability to sequester alkaloids, and changing daily activity patterns evolve together.

Daly, J. W. 1998. Thirty Years of Discovering Arthropod Alkaloids in Amphibian Skin. Journal of Natural Products 61:162-172.

Rodríguez, A., Poth, D., S. Schulz, and M. Vences. 2010. Discovery of skin alkaloids in a miniaturized eleutherodactylid frog from Cuba. Biology Letters doi: 10.1098/rsbl.2010.0844


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