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

Coleoid cephalopods (squids, 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 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 identified 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 understand cephalopod innovations. Overall design: We are using Hi-C and Atac-seq data of developing Euprymna scolopes embryos to understand if and how genome re-oragization affects regulation in cephalopods

鞘亚纲头足类（鱿鱼、乌贼、章鱼）是无脊椎动物中神经系统最为发达的类群，加之诸多类群特异性形态特征，使其演化出复杂的行为模式。这类创新性状背后的基因组学基础至今仍未明晰。本研究以模式生物夏威夷短尾鱿鱼（Euprymna scolopes）为研究对象，运用比较基因组学与功能基因组学手段，揭示了头足类基因组独特的组学特征、拓扑结构及调控组织模式。研究发现，相较于其他动物类群，头足类基因组发生了大规模的结构重排，由此产生了数百个紧密连锁且演化上独特的微同线性基因簇 (microsyntenies)。这类新型微同线性基因簇对应着具有独特调控结构的拓扑结构域，并参与塑造复杂的基因表达模式。尤为关键的是，本研究鉴定出一类与头足类创新性状相关的微同线性基因簇 (microsyntenies associated with cephalopod innovations，缩写为MACIs)，这类区域在头足类神经系统的基因表达中显著富集。本研究推测，MACIs的出现对头足类神经系统的演化起到了关键推动作用，并提出微同线性特征分析将成为解析头足类创新性状的核心手段。整体实验设计：本研究利用发育阶段的夏威夷短尾鱿鱼（Euprymna scolopes）胚胎的Hi-C（高通量染色体构象捕获技术）与ATAC-seq（转座酶可及性染色质测序）数据，探究头足类基因组重排是否以及如何影响其基因调控过程。