  In order to study unknown proteins on a large scale, a reference system has
been set up for the three major eukaryotic lineages, built with 36 proteomes as
taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with
no known homologue in this set were then analyzed, focusing noteworthy on
singletons, that is, on unknown proteins with no known homologue in their own
proteome. Consistently, according to Uniprot, for a given species, no more than
12% of the singletons thus found are known at the protein level. Also, since
they rely on the information found in the alignment of homologous sequences,
predictions of AlphaFold2 for their tridimensional structure are usually poor.
In the case of metazoan species, the number of singletons seems to increase as
a function of the evolutionary distance from the reference system.
Interestingly, no such trend is found in the cases of viridiplantae and fungi,
as if the timescale on which singletons are added to proteomes were different
in metazoa and in other eukaryotic kingdoms. In order to confirm this
phenomenon, further studies of proteomes closer to those of the reference
system are however needed.
