Z-chromosome dosage compensation and a male-specific lncRNA in octopus

Abstract

Sex chromosomes typically present as two copies of a large, gene-rich differentiated chromosome in the homogametic sex (e.g. XX in female mammals, ZZ in male birds) but as a single copy in the heterogametic sex, often paired with a sex-specific, degenerated chromosome (XY in male mammals, ZW in female birds). This creates a significant gene product dosage imbalance of the X and Z chromosomes between the sexes as well as between the single sex chromosome and the autosomes in the heterogametic sex, making its resolution essential. Dosage compensation and its molecular mechanisms have primarily been studied in select organisms, such as primates, rodents, birds, fruit flies, and Caenorhabditis elegans, while the extent and mechanisms of dosage compensation remain largely unexplored in the vast majority of animal taxa. Recently, coleoid cephalopods, including octopuses, squids, and cuttlefish, were reported to possess a ZZ/Z0 sex chromosome system1, where males carry two copies of the Z chromosome while females carry only one. However, whether dosage compensation occurs in these species remains unexplored. Here, we show, for the first time, that Z-chromosome dosage compensation is achieved in octopus. Using both original RNA-seq data from O.vulgaris paralarvae as well as publicly available datasets from O.vulgaris and O.sinensis, we report extensive but incomplete dosage compensation of the Z-chromosome in female octopus at the RNA level, similar to Z-chromosome dosage compensation in avian ZW systems. Furthermore, we identify two evolutionarily conserved Z-linked lncRNAs, one featuring strong male-biased expression patterns, that we termed "Zmast" and another with strong female-biased expression patterns that we termed "Zfest". Our results provide the first evidence of sex chromosome dosage compensation in octopus, representing one of the most ancient known animal sex-chromosome systems, and raise the possibility that non-coding RNA may play a role in its regulation, akin that observed in younger animal taxa.