Presenilin proteins are very well conserved across the eukaryotes. However, two of the three C. elegans genes are among the most divergent presenilin genes known. Only
sel-12 is highly similar to human PS1 and PS2 while both
spe-4 and
hop-1 are more divergent. I have identified all presenilin genes from many Nematode species (>20) across the phylum from public databases. I have found that in Nematodes, there are three classes of presenilin genes: 1) conserved standard presenilins, 2) divergent standard presenilins and 3)
spe-4 presenilins. The three C. elegans presenilins fit into each of these three classes:
sel-12 is a conserved standard presenilin,
hop-1 is a divergent standard presenilin and
spe-4 is a
spe-4 presenilin. In the nematode phylum, all species have at least one, and usually only one, conserved standard presenilin. These genes share high similarity to the human presenilins and have a large number of residues that are absolutely, or very strongly, conserved. All species within clades III, IV and V (according to the classification of Blaxter and colleagues) also contain a
spe-4 gene. SPE-4 proteins have several conserved residues and other features that differ from canonical presenilins. This suggests that
spe-4 genes may have evolved different functions, or interactions, from standard presenilins. The divergent standard presenilin genes encode proteins with highly divergent sequences that do not contain any highly conserved amino acids not found in conserved standard presenilins. These genes are rapidly diverging, indicating that they are under relaxed selection. The divergent standard presenilins arose from one or more ancient gene duplications. In the basal nematode species Trichuris muris there is both a conserved and a divergent standard presenilin. This, and the deep differences between SPE-4 proteins and conserved standard Presenilins, makes it likely that SPE-4 proteins evolved from an already divergent presenilin gene rather than a conserved standard presenilin. This means that a divergent presenilin gene was present in the last common ancestor of the Clades, III, IV and V species (about 500-400 million years ago).