JmjC Domain-Encoding Genes Are Conserved in Highly Regenerative Metazoans and Are Associated with Planarian Whole-Body Regeneration
JmjC Domain-Encoding Genes Are Conserved in Highly Regenerative Metazoans and Are Associated with Planarian Whole-Body Regeneration
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DOI：
10.1093/gbe/evz021
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发表时间：
2019-02-01
影响因子：
3.3
通讯作者：
Makino, Takashi
中科院分区：
文献类型：
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作者：
Cao, Ping-Lin;Kumagai, Nobuyoshi;Makino, Takashi
后生动物的再生能力差异很大，但人们对导致这种不同再生能力的进化过程知之甚少。特别是，涡虫和刺胞动物等具有高度再生能力的物种可以从截断的碎片中再生出整个身体。然而，这些物种之间的共同分子基础（如果有的话）仍不清楚。在这里，我们证明编码包含 Jumonji C (JmjC) 结构域的蛋白质的基因与高再生能力相关。我们将 132 个完全测序的后生动物分为具有高再生能力和低再生能力的两组，并鉴定了高再生组中保守的 118 个基因，这些基因在低再生组的物种中在进化过程中丢失。其中 96% 是 JmjC 结构域编码基因。我们将候选基因表示为高再生物种特异性 JmjC 结构域编码基因 (HRJD)。根据系统发育分析，我们观察到 Helobdella robsta 中 HRJD 的丢失，在进化过程中失去了高再生能力。通过RNA测序分析，我们观察到HRJD直系同源物在两种刺胞动物以及扁形动物和尾索动物（高度再生物种）的再生过程中存在差异表达。此外，在 HRJD 直向同源物的 RNA 干扰后，截肢涡虫 (Dugesia japonica) 的头部和尾部超过 50% 在再生过程中死亡。这些结果表明 HRJD 与后生动物的高再生能力密切相关。 HRJD 旁系同源物通过组蛋白去甲基化调节基因表达；因此，HRJD可能与再生过程中控制干细胞更新和干细胞分化的表观遗传调控有关。我们认为 HRJD 在再生过程中的表观遗传调控中发挥核心作用。
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.