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Some animals, especially those that have been around for a long time in evolutionary terms, possess extraordinary abilities to regenerate lost limbs or organs. These animals, such as flatworms, salamanders and zebrafish, are not at all closely related, suggesting that the ability to regenerate goes far back in evolutionary time. Is it possible to find a common set of genes for regeneration, that could unlock a new understanding of this process? 

Well, no, according to a recent study by scientists at the �����о��� and Caltech. A comparison of the expression of thousands of genes from six animals capable of extensive regeneration (axolotl, zebrafish, anemone, flatworm, sea sponge and sea cucumber) found little evidence of a core conserved trait, but does point to some new areas to investigate. The study was . 

“We’re looking at genes that control regeneration in many animals that are not closely related,” said associate professor in the �����о��� Department of Earth and Planetary Sciences. “Is it an ancient trait that we have lost, or did different animals arrive at it independently?”

Comparing RNA sequences

Noémie Sierra, a graduate student in Gold’s lab, developed a novel approach to compare publicly available RNA sequence data for these six animals. RNA sequencing identifies genes that are actively producing proteins. It has previously been very difficult to compare this kind of data across species and studies, Gold said. 

Sierra and Gold’s approach combined orthologous (similar) genes into clusters and used a novel statistical method to look for enrichment of particular genes. 

However, their analysis provided little support for the hypothesis of a shared, ancestral set of regeneration genes, with the possible exception of a family of signaling genes called Wnt. 

“We know Wnt signaling is important, but this is a big family of genes and they all use different versions,” Gold said. Most of the genes sorted into the orthologous clusters have a structural function -- building body tissues.

Perhaps ironically, the study shows that large-scale comparisons of RNA across widely divergent species in not a useful approach for this particular problem. 

“We have to move past broad comparisons into a deeper study of model animals,” Gold said. 

Coauthors on the paper are Noah Olsman, Lynn Yi, Lior Pachter and Lea Goentoro at the Caltech. The work was supported in part by the National Science Foundation.