Concerted regulation and molecular evolution of the duplicated SNRPB '/B and SNRPN loci

The human small nuclear ribonucleoprotein SNRPB'/B gene is alternatively sp liced to produce the SmB or SmB' spliceosomal core proteins, An ancestral d uplication gave rise to the closely related SNRPN paralog whose protein pro duct, SmN, replaces SmB'/B in brain. However, the precise evolutionary and functional relationship between these loci has not been clear. Genomic, cDN A and protein analyses presented here in chicken, two marsupials (South Ame rican opossum and tammar wallaby), and hedgehog, suggest that the vertebrat e ancestral locus produced the SmB' isoform, Interestingly, three eutherian s exhibit radically distinct splice choice expression profiles, producing e ither exclusively SmB in mouse, both SmB and SmB' in human, or exclusively SmB' in hedgehog, The human SNRPB'/B locus is biallelically unmethylated, u nlike the imprinted SNRPN locus which is unmethylated only on the expressed paternal allele, Western analysis demonstrates that a compensatory feedbac k loop dramatically upregulates SmB'/B levels in response to the loss of Sm N in Prader-Willi syndrome brain tissue, potentially reducing the phenotypi c severity of this syndrome, These findings imply that these two genes enco ding small nuclear ribonucleoprotein components are subject to dosage compe nsation, Therefore, a more global regulatory network may govern the mainten ance of stoichiometric levels of spliceosomal components and may constrain their evolution.