Mapping Frog, Newt Genomes for Medical Discovery

The golden poison dart frog (Phylobates terribilis) is one of the most toxic animals in the world. The frogs, which measure only five centimeters, have enough poison to kill ten grown men.

The toxin in these frogs is so effective, explains Denis Machado, a doctoral student from the Inter-units Graduate Program in Bioinformatics at the University of São Paulo (USP), that the indigenous Emberá people of Colombia have used it for centuries to tip their blowgun darts for hunting, giving the species its name.

Yet, the poison does not affect the frogs.

Machado, who is studying at UNC Charlotte as part of the São Paulo Research Foundation Research Internship Abroad program, notes that most of the 7,513 species of amphibians possess toxins. They are mainly accumulated in poison glands on their skin and are part of their immune system fighting bacterial and viral infections. Machado’s research focuses on understanding the genomic basis behind the anuran or frog family’s ability to produce, sequester and resist a variety of defensive toxins.

He is working with the David H. Murdock Research Institute’s (DHMRI) Genomics Laboratory and Dan Janies, PhD, from the UNC Charlotte’s department of Genomics and Bioinformatics, to use RNA-Seq and genomic sequencing to examine specific characteristics of amphibians with different toxin profiles such as the presence and absence of lipophilic alkaloids, endogenously biosynthesized indolalkylamine and neurotoxins such as tetrodotoxin (TTX).

RNA-Seq

TTX is found in a diverse array of taxa including bacteria, mollusks, pufferfish, flatworms, newts and frogs. The origins of the toxins are unknown, but it works by interfering with voltage-gated sodium channels causing paralysis.  Research led by Taran Grant, PhD, in the laboratory of amphibians in the Department of Zoology at USP, indicates a genetic origin. 

The DHMRI Genomics Laboratory will use RNA-Seq,  a technology in which all of the active genes are sequenced, to study the transcriptomes of frogs in the genus Brachycephalus and different populations of the rough skin newt Taricha granulosa, which both bioaccumulate TTX. Machado will compile a candidate list of possible genes associated with bioaccumulation and resistance with the results.

“We are working with the hypothesis that amphibians acquire genes that allow them to produce TTX in their cells,” he said. “The hypothesis is supported by histology and chemical experiments that we have conducted. RNA-Seq should give us a clearer answer as to whether or not those animals have genes that produce TTX.”

Genomic Sequencing

In comparison to RNA-seq, genomic sequencing captures the active, regulatory and other non-coding DNA. Machado is working with DHMRI to sequence the genome of the golden blow dart frog in comparison to its closest, less toxic anuran relative to gain insight into how the frogs sequester and resist the toxins they produce. The sequencing, Machado explained, should “unveil the first clues” of the evolution of toxins in poison dart frogs, and reveal information that will be useful for advancing medical research on the use of the golden frog's poison for painkillers with lower risks for developing resistance and addiction in patients. The toxins may also have antibacterial and antiviral properties that could be tapped for drug development.

At DHRMI, Machado has found a distinct advantage. “They are very responsive, easy to talk to and always have good advice on how to conduct experiments,” he said. “They are very interested in our work, and it seems to me that the people at DHMRI actually understand more about biology than other companies. Their scientists provide a multi-disciplinary understanding of our project that is helping us a lot.”

Learn more about the DHMRI’s Genomics Laboratory.

Back to News