All eukaryotes so far studied, including animals, plants, yeasts and trypan
osomes, have two pathways to target proteins to peroxisomes. These two path
ways are specific for the two types of peroxisome targeting signal (PTS) pr
esent on peroxisomal matrix proteins. Remarkably, the complete genome seque
nce of Caenorhabditis elegans lacks the genes encoding proteins specific fo
r the PTS2 targeting pathway. Here we show, by expression of green fluoresc
ent protein (GFP) reporters for both pathways, that the PTS2 pathway is ind
eed absent in C. elegans. Lack of this pathway in man causes severe disease
due to mislocalization of PTS2-containing proteins. This raises the questi
on as to how C. elegans has accommodated the absence of the PTS2 pathway. W
e found by in silico analysis that C. elegans orthologues of PTS2-containin
g proteins have acquired a PTS1. We propose that switching of targeting sig
nals has allowed the PTS2 pathway to be lost in the phylogenetic lineage le
ading to C. elegans.