Tadpole's ability to regrow limbs removed by cutting out one gene

Researchers have removed the ability of frog tadpoles to regrow amputated tails or limbs by blocking the expression of a newly identified gene.

The research, published in the journal Cell Reports, suggests that the loss of appendage regeneration in warm-blooded animals might have been caused by the gain or loss of this gene, dubbed c-Answer, in an ancestor's genome during evolution.

"We suppose that genes can only disappear if removing them has advantages for the animal," said Daria Korotkova, from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry in Russia.

"So, we suggest that when this gene disappeared from warm-blooded species it was by a mutation, acting as a trade-off for the loss of appendage regeneration," Korotkova said.

Using a computer algorithm, the researchers identified several genes that disappeared in the genomes of warm-blooded vertebrates, including humans, but are present in cold-blooded ones.

They did this by searching the DNA of African clawed frogs, Xenopus laevis, to determine which genes code for regeneration.

The team then looked for similar DNA patterns in warm-blooded species, such as chicks, and noted anywhere a gene differed.

The researchers then selected one of the identified cold-blooded specific genes, encoding for previously unknown transmembrane protein, and named it c-Answer.

The research team over-expressed or blocked c-Answer in tadpole embryos.

They discovered that enhancing c-Answer allowed tadpoles to regenerate lost tails earlier in their life than those that hatched naturally, whereas tadpoles with c-Answer blocked could transition into frogs but could not regenerate amputated appendages.

"C-Answer modulates at least two important molecular pathways that are common to all vertebrates," said Andrey Zaraisky, from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry.

"Its loss in evolution might alter the functioning of these pathways and, accordingly, lead to major physiological transformations," Zaraisky said.

The researchers found that over expression of c-Answer causes advanced brain growth and larger eyes, which was surprising because it means c-Answer modulates for regeneration and brain development.