Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

Abstract

Coleoid cephalopods (squid, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that coleoid cephalopod genomes have been extensively restructured compared to other animals, leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identify a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understanding cephalopod innovations.

Genome and transcriptome mechanisms driving cephalopod evolution

“…The E. scolopes assembly was generated using HiC data and assembled with Lachesis 72 , 73 . Scaffolds of 50 kb and longer from the publicly available 27 assembly were used together with aligned Hi-C reads.…”

Epigenetic machinery is functionally conserved in cephalopods

“…The vast majority of the O. bimaculoides genome is intergenic and nearly half of the genome is occupied by repetitive sequences [ 26 , 29 , 71 ]. Over 85% of CpGs in the octopus genome were intergenic (Fig.…”

“…The role of epigenetics in cell identity, plasticity, development, behavior, and disease is one of the most investigated aspects of biology; however, the role of epigenetics in the distinct transcriptomic profiles in coleoid cephalopods has not been investigated. Moreover, as the 3D genome and genome evolution are dictated by chromatin structure, epigenetics could also contribute to the unique features of cephalopod genomes [ 26 – 29 , 72 , 73 ]. We described a tissue-specific gene expression pattern in adult octopus and provided an annotation of octopus transcripts that can be integrated with the recently published O. bimaculoides genome annotation [ 27 ].…”

“…Single-cell analysis would also be an ideal approach to differentiate between the mix of tissues present in samples from hatchlings. Moreover, as the genomes of other cephalopods have been sequenced recently [ 26 , 27 , 73 , 74 ], conclusions about common epigenetic mechanisms across these animals awaits more extensive comparative epigenomic analysis.…”

“…This is not the case in O. bimaculoides , where half the genome is populated by repetitive elements similarly to vertebrates [ 29 ]. Interestingly, the level of DNA methylation is not proportional to the transposon load in this genome [ 22 ], and there is a high level of TE expression in octopus tissues, especially in the brain [ 26 , 29 , 31 ]. This warrants investigation of the function of DNA methylation in these animals.…”