BACKGROUND: Ubiquilins are proteins that function as ubiquitin receptors in 
eukaryotes. Mutations in two ubiquilin-encoding genes have been linked to the 
genesis of neurodegenerative diseases. However, ubiquilin functions are still 
poorly understood.
RESULTS: In this study, evolutionary and functional data are combined to 
determine the origin and diversification of the ubiquilin gene family and to 
characterize novel potential roles of ubiquilins in mammalian species, including 
humans. The analysis of more than six hundred sequences allowed characterizing 
ubiquilin diversity in all the main eukaryotic groups. Many organisms (e. g. 
fungi, many animals) have single ubiquilin genes, but duplications in animal, 
plant, alveolate and excavate species are described. Seven different ubiquilins 
have been detected in vertebrates. Two of them, here called UBQLN5 and UBQLN6, 
had not been hitherto described. Significantly, marsupial and eutherian mammals 
have the most complex ubiquilin gene families, composed of up to 6 genes. This 
exceptional mammalian-specific expansion is the result of the recent emergence 
of four new genes, three of them (UBQLN3, UBQLN5 and UBQLNL) with precise 
testis-specific expression patterns that indicate roles in the postmeiotic 
stages of spermatogenesis. A gene with related features has independently arisen 
in species of the Drosophila genus. Positive selection acting on some mammalian 
ubiquilins has been detected.
CONCLUSIONS: The ubiquilin gene family is highly conserved in eukaryotes. The 
infrequent lineage-specific amplifications observed may be linked to the 
emergence of novel functions in particular tissues.