Rapid regeneration from tiny pieces of tissue makes planarians a prime model system for regeneration. Abundant adult pluripotent stem cells, termed neoblasts, power regeneration and the continuous turnover of all cell types1,2,3, and transplantation of a single neoblast can rescue a lethally irradiated animal4. Planarians therefore also constitute a prime model system for stem cell pluripotency and its evolutionary underpinnings5. The taxonomic clade Platyhelminthes (‘flatworms’) also includes parasitic lineages that have substantial effects on human health, such as blood flukes (Trematoda) and tape worms (Cestoda)6. Here, the phylogenetic position of planarians as free-living flatworms7 provides a reference point towards an understanding of the evolution of parasitism8.

Despite the modest genome sizes of planarians (mostly in the range of 1–2 gigabase pairs (Gb)), genome resources relating to these animals are limited. Although the model species S. mediterranea was sequenced by Sanger sequencing, even 11.6× coverage of around 600-bp Sanger reads yielded only a highly fragmented assembly (N50 19?kb)9. Recent high-coverage, short-read approaches yielded similarly fragmented assemblies10,11. The high A–T content (about 70%) represents one known assembly challenge. Furthermore, standard DNA isolation procedures perform poorly on planarians, which has so far precluded the application of long-read sequencing approaches or BAC-clone scaffolding.

We here report a highly contiguous PacBio SMRT long-read sequencing12 assembly of the S. mediterranea genome. Giant gypsy/Ty3 retroelements, abundant AT-rich microsatellites and inbreeding-resistant heterozygosity collectively provide an explanation for why previous short-read approaches were unsuccessful. We find a loss of gene synteny in the genome of S. mediterranea and other flatworms. In analysis of highly conserved genes, we find a loss of MAD1 and MAD2, suggesting a MAD1–MAD2-independent spindle assembly check point (SAC)13,14. Our S. mediterranea genome assembly provides a resource for probing the evolutionary plasticity of core cell biological mechanisms, as well as the genomic underpinnings of regeneration and the many other phenomena that planarians expose to experimental scrutiny.