JmjC domain-encoding genes are conserved in highly regenerative metazoans and are associated with planarian whole-body regeneration

Ping Lin Cao, Nobuyoshi Kumagai, Takeshi Inoue, Kiyokazu Agata, Takashi Makino

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


The capacity for regeneration varies greatly among metazoans, yet little is known about the evolutionary processes leading to such different regeneration abilities. In particular, highly regenerative species such as planarians and cnidarians can regenerate the whole body from an amputated fragment; however, a common molecular basis, if any, among these species remains unclear. Here, we show that genes encoding Jumonji C (JmjC) domain-containing proteins are associated with high regeneration ability. We classified 132 fully sequenced metazoans into two groups with high or low regeneration abilities and identified 118 genes conserved in the high regenerative group that were lost in species in the low regeneration group during evolution. Ninety-six percent of them were JmjC domain-encoding genes. We denoted the candidate genes as high regenerative species-specific JmjC domain-encoding genes (HRJDs). We observed losses of HRJDs in Helobdella robusta, which lost its high regeneration ability during evolution based on phylogenetic analysis. By RNA sequencing analyses, we observed that HRJD orthologs were differentially expressed during regeneration in two Cnidarians, as well as Platyhelminthes and Urochordata, which are highly regenerative species. Furthermore, >50% of the head and tail parts of amputated planarians (Dugesia japonica) died during regeneration after RNA interference of HRJD orthologs. These results indicate that HRJD are strongly associated with a high regeneration ability in metazoans. HRJD paralogs regulate gene expression by histone demethylation; thus, HRJD may be related to epigenetic regulation controlling stem cell renewal and stem cell differentiation during regeneration. We propose that HRJD play a central role in epigenetic regulation during regeneration.

Original languageEnglish
Pages (from-to)552-564
Number of pages13
JournalGenome biology and evolution
Issue number2
Publication statusPublished - 2019 Feb 1


  • Evolution
  • Histone demethylation
  • JmjC domain
  • RNA-Seq
  • Regeneration

ASJC Scopus subject areas

  • Medicine(all)


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