Adaptive Innovation in the Octopus Ribosome

Abstract

The ribosome is the universal machine for protein synthesis across all life. All ribosomes consist of a conserved core of ribosomal proteins and RNAs (rRNAs) that mediate accurate decoding of mRNAs to synthesize functional proteins. In agreement, biochemical or genetic disruptions to translation fidelity cause cellular death and severe cognitive or aging related defects. In this thesis, I describe a completely serendipitous discovery, where we find that the 28S rRNA of the octopus contains a novel “break” in the highly conserved catalytic ribosomal RNA (rRNA) core of the ribosome. This rRNA break is unique to octopus species and not found among all analyzed animals, including closely related squid or cuttlefish, or distant mollusks, invertebrates, or vertebrates. By obtaining a cryo-EM structure of the O. bimaculoides ribosome, we find that the octopus rRNA break is found in the E-site near the site of deacylated tRNA binding. We then postulate that octopus rRNA break enhances translation fidelity by allosterically decreasing A-site tRNA binding affinity during decoding. Later studies focused on how evolution of this break ultimately supports novel traits which emerged in octopuses. We find that the increased accuracy leads to less protein misfolding and aggregation and a reduced basal unfolded protein response in vivo in octopus compared to other cephalopods or mollusks. This advantage for proteostasis supports the expanded nervous systems of the animal. Notably, we also observe that the octopus ribosome innovation contributes to organismal plasticity. Octopus and squid exhibit unusually high levels of ADAR editing, with extensive adenosine-to-inosine recoding in the coding regions of transcripts. Editing increases in response to the environment, and has been hypothesized to contribute to protein recoding. We find that the octopus rRNA break controls how inosines are decoded during mRNA translation. This allows octopus to have higher organismal plasticity and regulation of the proteome than squid upon exposure to changes to environmental conditions such as cold temperature. In summary, our findings reveal how evolution of the ribosome allows for organismal-specific adaptations to protein synthesis. While much of biology has demonstrated how the genetic code drives evolution, it is less understood how evolution can be driven by adaptations in other components of the central dogma. Here, we discover how the octopus uses modifications in the core protein synthesis machinery to drive biological novelty, a strategy which could support the evolution of unique organismal traits across life.