An international team of researchers led by Karolinska Institutet scientists has successfully sequenced and analyzed the genome of a species of salamander called the Iberian ribbed newt (Pleurodeles waltl). Among the team’s findings is a family of genes that can provide clues to the unique ability of salamanders to rebuild complex tissue. The results are published in the journal Nature Communications.
Iberian ribbed newts (Pleurodeles waltl). Image credit: Peter Halasz / CC BY-SA 3.0.
“Among tetrapods, salamanders, such as newts and axolotls, display the largest regenerative repertoire. A newt can rebuild entire limbs, tails, jaws, cardiac muscle, ocular tissues, and restore central nervous system tissues including brain structures,” said Karolinska Institutet’s Professor András Simon and co-authors.
“However, major differences exist even among salamanders. In contrast to axolotls, newts undergo metamorphosis, have a broader regeneration spectrum and mobilize additional cell sources for regeneration of the same body part.”
To gain new insights into this striking regenerative ability, the researchers sequenced the genome of the Iberian ribbed newt, a salamander species endemic to the central and southern Iberian Peninsula and Morocco.
They found that the newt genome has about 20 billion DNA base pairs — a full six times greater than the human genome.
They also successfully identified 14,805 protein-coding genes in the genome.
“We believe that our achievement can give rise to new discoveries on the amphibian’s ability to recreate brain neurons as well as entire body parts,” the authors said.
Among the first findings is a multitude of copies of a certain microRNA group, which in mammals is mainly found in embryonic stem cells, but also in tumor cells.
“It will be exciting to figure out how regeneration in the adult organism re-activates embryonic genes,” Professor Simon said.
“What’s needed now are functional studies of these microRNA molecules to understand their function in regeneration.”
“The link to cancer cells is also very interesting, especially bearing in mind newts’ marked resistance to tumor formation.”
Even though the abundance of stem cell microRNA genes is quite surprising, it alone cannot explain how salamanders regenerate so well.
“We think that the explanation lies in a combination of genes unique to salamanders and how other more common genes orchestrate and control the actual regeneration process,” the scientists said.
They now engaging with other researchers to discover what can be learned from the newt genome and test new hypotheses through systematic comparisons with mammals.
“We showed 10 years ago that salamanders can recreate all the cells that die in Parkinson’s disease in the space of four weeks,” Professor Simon said.
“We can now delve deeply into the molecular processes underlying this ability. Although we’re doing basic research, our findings can hopefully lead to the development of new regenerative strategies for humans.”
_____
Ahmed Elewa et al. 2017. Reading and editing the Pleurodeles waltl genome reveals novel features of tetrapod regeneration. Nature Communications 8, article number: 2286; doi: 10.1038/s41467-017-01964-9
