Thea F. Rogers, University of Vienna/Daniel Mendéz-Aranda, Max Delbrück Center Berlin

3D genome organisation, gene regulation, and the evolution of novel traits in Cephalopods (Rogers) / Convergence of pain insensitivity in a new species of Heliphobius mole-rat (Mendéz-Aranda)

Rogers: Our understanding of how genomic changes translate into organismal novelties is often confounded by complex and multi-layered genome architecture, and the deep evolutionary time-scales over which genomic innovations can accumulate. Coleoid cephalopods (squid, cuttlefish and octopus) offer a unique system in which to study the impact of macroevolutionary genomic processes on phenotypic complexity. A large-scale chromosomal rearrangement in the coleoid ancestor (~450 MYA) resulted in an extensively modified karyotype and is hypothesized to underpin the evolution of coleoid innovations, including their large and elaborately structured nervous system, novel organs, and complex behaviours such as their dynamic camouflaging ability. Following this shared genomic shift, Decapodiformes (squid and cuttlefish) and Octopodiformes (octopuses and vampire squid) have also followed distinct evolutionary trajectories, shaped by lineage-specific chromosomal changes including fusions, translocations, repetitive element expansions, and tandem gene duplications. Yet, how these large-scale genomic processes have impacted regulatory architecture remains poorly understood. To address this, we integrate Micro-C, RNA-seq and ATAC-seq data across multiple coleoid species, developmental stages, and tissues, and examine syntenic genes, topological interactions and conserved non-coding elements (CNEs). We find that topological compartments tend to be conserved, yet exhibit divergent evolutionary paths depending on their ancestral context. In contrast, hundreds of putative regulatory chromatin loops are species-specific and often show stage- or tissue-specific activity with complex expression dynamics. Evolutionary analysis of such structures reveals a tendency of fusion and mixing in the octopus lineage, making it a more derived regulatory state. Furthermore, CRISPR knock-out of putative regulatory sequences within one such conserved region highlights its role in neural development. We propose that varying levels of relaxed evolutionary constraints on the coleoid 3D genome enables clade-specific patterns of chromosomal rearrangement and expansion, facilitating the emergence of novel regulatory configurations underlying complex traits in the coleoids. // Mendéz-Aranda: A newly identified Heliophobius mole-rat from Tanzania’s Usambara Mountains shows insensitivity to acid and capsaicin, mirroring the phenotype of the naked mole-rat (Heterocephalus glaber). Genomic analysis revealed the same key mutations in the SCN9A gene (Nav1.7) in both species, suggesting convergent evolution. Phylogenomic data support the classification of the Usambara mole-rat as a distinct species, providing a powerful model for studying the evolution of pain insensitivity.