Impact of transposable elements during animal regeneration

Regeneration capabilities vary significantly across multicellular animals. The underlying molecular mechanisms and their evolution are being studied in various well-established model organisms. The major focus so far has been on the protein-coding genes and their regulation. The role of the non- coding genome that comprises the majority of the DNA remains elusive. With the modern technologies of genome studies, only recently the non-coding portion of the genome begins to be studied. Out of non-coding regions, transposable elements comprise the largest portion. Recent data showing the activation of specific transposons during regeneration. Interestingly, on the evolutionary time-scale, their elevated numbers also contribute to the characteristic large genome size of many species capable of extraordinary regeneration. Those insights pose key, still unanswered questions regarding their roles both during the actual process of regeneration as well as a potential evolutionary role in facilitating regeneration capabilities. This proposal will compare the activation of transposons during regeneration and their effect on the genome architecture in two key model systems of regeneration, the cnidarian Hydra magnipapillata and the vertebrate, salamander, Ambystoma mexicanum (axolotl). Initially using bioinformatic approaches we will characterize the shared and derived transcriptionally active transposable elements among those two species, providing the first complete overview of regeneration-active elements at the sub-family resolution level. Then we will study cellular-level activity and insertion sites of transposons in regenerating tissues. We will then functionally test a subset of those insertions to assess their effect on regeneration. We will finally utilize latest DNA sequencing technologies to study genome-wide transposon insertion dynamics in regenerating tissues. Such data will reveal, for the first time, the general involvement of transposons during regeneration and any functional role during development. The whole-genome study will also reveal the extent to which a metazoan genome is affected during each regenerative cycle, providing crucial insights into the genome stability, response, as well as modifications to its structure. Our evolutionary comparison of genomic responses during vertebrate and cnidarian regeneration will unravel common and unique patterns of how metazoan genome architecture has permitted the extraordinary regenerative capabilities in those clades shedding light on both evolvability of the regeneration programme as well as the functional implications for biomedical research.

In this project, we examined whether "jumping genes" called transposons are active and play a role in regeneration of invertebrate and vertebrate animals. We found evidence that indeed, transposons are active during regeneration and in Hydra, have caused the constituent cell layers of the animal to accumulate differences in their genomic sequences. We are currently examining how the insertion of these transposons affects the usage of genes during regeneration.