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.