In the Giant Salamander Genome, a Quest to Unlock a Regeneration Mystery

The salamander genome is one of the biggest to have been sequenced and assembled. Scientists think the size of it could have something to do with the amphibian’s ability to regenerate lost limbs.

An X-ray of a salamander. Most salamanders are 10-20 cm long. Credit: Franco Andreone/Wikimedia Commons, CC BY-SA 2.5

An X-ray of a salamander. Most salamanders are 10-20 cm long. Credit: Franco Andreone/Wikimedia Commons, CC BY-SA 2.5

Catching a gecko by its tail is probably not a good idea. Before you know it, the lizard is going to detach its tail and escape. But fear not for the crawler – it can regenerate the lost part completely within two weeks.

Regeneration is a process by which the cells in an organism’s body reorganise their numbers, function and location to replace a lost part. It is a survival mechanism widely seen in jellyfish, sponges, flatworms, insects and many crustaceans. Salamanders are genetically the closest organisms to humans that can regrow lost limbs, so they have been widely studied by researchers for understanding how regeneration works.

The precise mechanism by which salamanders could regenerate lost parts had eluded scientists. This was because their genetic makeup was not thoroughly understood. If it was, scientists could’ve compared the information with non-regenerating organisms and say which group of genes in salamanders were likely to be involved in regeneration.

Recently, researchers from the Karolinska Institutet, Stockholm, sequenced the genome of a salamander – the Iberian ribbed newt – and surveyed its genes. They found that a class of small genes called microRNA, made of about 44 molecules, is involved in regeneration.

“Our study has found that some microRNAs normally produced in the embryo are reactivated in the adult salamander after injuries like limb amputation,” said Ahmed Elewa, a postdoctoral researcher and the study’s corresponding author. MicroRNA have been known to play a major role in regulating the production of proteins in cells.

Elewa and co. also found another class of genetic materials involved in regeneration, called jumping genes. These genes are known to move from one location of the genome to another, and are thus capable of regulating other genes. “A special class of jumping genes called Harbinger transposable elements are spread across the salamander genome and this lead us to suspect that some of the genes they move on to are important for regeneration as well,” Elewa added.

He also noted that skeletal muscle regeneration in salamanders followed a different mechanism from that in humans. In mammals, muscle development requires the function of two genes called Pax7 and Pax3; the team found that salamanders could regrow functional limbs even when these genes were deactivated.

Scott T. Dougan, a developmental biologist at the University of Georgia, called the study a “technological tour de force”. The most important result of the study according to him was that the genes involved in muscle development were not influencing limb regeneration. “It remains to be determined if this is a species-specific result or if it is more generally true of limb regeneration in other animals.”

Dougan added that this was one of the biggest vertebrate genomes ever sequenced and assembled. If, for example, data from the human genome weighed 3 GB, the salamander genome contained about 20 GB of genetic information. At the same time, the number of protein-coding genes identified was roughly equal to those in the human genome, prompting researchers to wonder what other functions these genes had.

According to the study, the large size of the salamander’s genome seems to be due to a large number of jumping genes. “The authors provide interesting evidence that suggests some of the jumping genes may be responsible for this animal’s extensive regenerative capacity. But this point needs further research,” Dougan said.

K. VijayRaghavan, a developmental biologist at the National Centre for Biological Sciences, Bengaluru, commended the research team for its valuable description of the salamander genome. He added that the results discussing the deactivation of the Pax3 and Pax7 genes were interesting – but also that it afforded many possible explanations. “The results raise many questions, which can be addressed through further research,” he said, echoing Dougan.

The Swedish study has valuable shed light on the salamander genome. The molecular mechanisms behind regeneration can now be understood like never before, and with it, Elewa and co. hope to develop new regenerative strategies for humans in the future.

The paper was published in the journal Nature Communications on December 22, 2017.

Vishwam Sankaran is a freelance science writer.

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