Previous studies [ 41, 42] reported an increase in both exon and intron conservation in the regions flanking conserved alternative splice sites.
Two contradicting properties have been associated to evolutionary conserved alternative exons: higher sequence conservation and higher rate of non-synonymous substitutions, relative to constitutive exons.
These "alternative exons" maintain conserved sequences for human-mouse orthology and conserved regulatory sequence elements for conserved alternative splicing.
NAGNAGs contribute 45% of all conserved alternative acceptors in H. sapiens and M. musculus [ 9].
Conserved alternative splicing gene list in rice, sorghum, corn, and Brachypodium distachyon.
In addition, by searching all annotated human genes, we identified a few other genes in which evolutionarily conserved alternative upstream AUG codons exist (similar situation as rTSβ).
In contrast to previous studies that were primarily interested in functional (e.g. conserved) alternative splicing of retained introns [ 8, 10], we did not enforce possible functionality.
Conserved alternative splicing patterns in plant SR splicing factors transcripts can be activated developmentally or by changes in external conditions such as environmental stresses [ 20- 22].
This indicates that highly conserved alternative exons must be strongly regulated by intron signals, since their pattern of ESE conservation is very similar to that of constitutive exons.
The other eutherian mammal genes have highly conserved alternative donor splice sites with those of dog and human, suggesting that they might also potentially express a similar alternative splicing variant.
For example, the core small nuclear ribonucleoprotein (snRNP) SmB/B′ self-regulates its expression by promoting the inclusion of a highly conserved alternative exon in its own pre-mRNA that targets the spliced transcript for NMD [ 17].
