Origin of Eukaryotic Plasmalogen Biosynthesis by Horizontal Gene Transfer from Myxobacteria

Plasmalogens, a unique class of membrane lipids defined by a distinctive vinyl ether bond, are critical for human health, with their altered levels linked to various diseases. Despite their importance, their origin and evolutionary history remain enigmatic. Here, we uncover the evolutionary history of the aerobic plasmalogen biosynthesis pathway in eukaryotes, focusing on the four essential enzymes responsible for their formation. Through comprehensive phylogenetic analyses and experimental validation, we demonstrate a significant divide in plasmalogen synthesis capabilities across major eukaryotic lineages. Our study also suggests that the acquisition of these plasmalogen biosynthesis genes by an early eukaryotic ancestor was through horizontal gene transfer (HGT) from Myxobacteria. The findings yield insights into how HGT shapes metabolic pathways and illuminate a critical step in the genesis of eukaryotic cell complexity.