Genomic insights into polyketide toxin synthesis and algal symbiosis using high-quality genome sequences of the early divergent hexacorallian genus Palythoa (Cnidaria, Zoantharia)

Palytoxin, first isolated from Palythoa toxica , is among the most potent marine toxins known. Despite decades of biochemical investigation, genetic bases underlying its potential biosynthesis in Palythoa remain unresolved. Here we present four high-quality genome assemblies of Palythoa species, including Palythoa cf. toxica , and integrate these with a chromosome-scale genome assembly of P. caribaeorum . Performing comparative genomic analyses, we screened for candidate genes potentially involved in palytoxin biosynthesis and examined patterns of genome evolution. Unexpectedly, we identified only two classes of ketosynthase (KS) domain-containing genes in Palythoa : fatty acid synthases (FAS) and bacterial-like polyketide synthases (PKSs). Contrasting other anthozoans, animal FAS-like PKS (AFPK) genes common to all Palythoa species were not detected. We found no evidence for lineage-specific expansion of PKS genes unique to Palythoa , suggesting that if palytoxin/palytoxin-like molecule biosynthesis is host-encoded, it may involve functional modification or co-opting pre-existing FAS and/or bacterial-like PKS pathways. Comparative analyses revealed expansions of gene families associated with transport and binding functions in Palythoa , potentially reflecting molecular adaptations linked to their sand-incorporating body structure. We identified TPT1 and CLEC4A as rapidly evolving genes in multiple Palythoa species, consistent with possible roles in growth regulation and host-microbe interactions. Additionally, comparison between azooxanthellate and zooxanthellate species revealed mutations within conserved protein domains of LePin, which has been implicated in cnidarian endosymbiosis, suggesting lineage-specific modifications associated with symbiotic state. This study establishes a foundation for zoantharian genomic research, provides insights into lineage-specific genomic signatures, and advances molecular and evolutionary biological knowledge of this ecologically important group.