An Integrative View on Multiple “Lipid Divide” Events as Hallmarks of Distinct Evolutionary Transitions

Lipids are fundamental to life, serving not only as membrane components but also as key players in signaling, energy storage, and cellular identity. While the well-known "lipid divide" between Bacteria and Archaea marks a major early evolutionary step, recent findings suggest that lipid-based divergences extend well beyond prokaryotic domains. In this Perspective, we highlight multiple lipid divergences that coincide with key phylogenetic splits, including the unikont-bikont or Opimoda-Diphoda separation, the Amoebozoa-Opisthokonta (Obazoa) and fungi-metazoa splits, the invertebrate-vertebrate transition, and even intragenus divergence. These divergences are often reflected in the lineage-specific presence or absence of lipid biosynthetic enzymes, regulatory proteins, and functional effectors. By mapping these molecular players alongside the lipid class distribution, we propose an expanded model of the lipid divide as a recurring hallmark of evolution. We believe this lipid-centric view will offer fresh insights into the molecular basis of cellular complexity and evolutionary innovation and encourage further investigation into additional, yet-unrecognized lipid divergence events.