An evolutionary analysis of lysophospholipid acyltransferases generating membrane phospholipid diversity.

All living organisms are enclosed by biological membranes composed primarily of phospholipids. The diversification of membrane lipids has shaped key membrane functions, including signaling, membrane protein regulation, and immune responses, and may also have driven organismal evolution. In humans, this diversity is mainly generated by lysophospholipid acyltransferases (LPLATs), yet the evolutionary distribution and diversity of LPLATs across organisms remain poorly understood, particularly in pathogens. Here, we systematically identified candidate LPLAT proteins belonging to two major families in representative prokaryotic and eukaryotic species and reconstructed their phylogenetic relationships. The analysis reveals a marked expansion and diversification of LPLATs in vertebrates and suggests the possibility of pathogen-specific LPLAT expansions. These findings suggest that the diversification of membrane phospholipid remodeling enzymes may accompany increasing biological complexity and pathogenicity. This study provides an evolutionary framework for understanding phospholipid metabolism and highlights pathogen LPLATs as potential targets for exploring host defense mechanisms.