A phylogenetic analysis of the lipocalin protein family

The lipocalins are a family of extracellular proteins that bind and transpo rt small hydrophobic molecules. They are found in eubacteria and a great va riety of eukaryotic cells, in which they play diverse physiological roles. We report here the detection of two new eukaryotic lipocalins and a phyloge netic analysis of 113 lipocalin family members performed with maximum-likel ihood and parsimony methods on their amino acid sequences. Lipocalins segre gate into 13 monophyletic clades, some of which are grouped in well-support ed superclades. An examination of the G+C content of the bacterial lipocali n genes and the detection of four new conceptual lipocalins in other eubact erial species argue against a recent horizontal transfer as the origin of p rokaryotic lipocalins. Therefore, we rooted our lipocalin tree using the cl ade containing the prokaryotic Lipocalins. The topology of the rooted lipoc alin tree is in general agreement with the currently accepted view of the o rganismal phylogeny of arthropods and chordates. The rooted tree allows us to assign polarity to character changes and suggests a plausible scenario f or the evolution of important lipocalin properties. More recently evolved l ipocalins tend to (I) show greater rates of amino acid substitutions. (2) h ave more flexible protein structures, (3) bind smaller hydrophobic ligands, and (4) increase the efficiency of their ligand-binding contacts. Finally, we found that the family of fatty-acid-binding proteins originated from th e more derived lipocalins and therefore cannot be considered a sister group of the lipocalin family.