Correlated Evolution of XXXX Positions within Splice Sites in Mammals.

@entity4334 @entity2036
UNASSIGNED: Splice sites (SSs)-short @entity4334 sequences flanking introns-are under selection for spliceosome binding, and adhere to consensus sequences. However, non-consensus @entity2036 , many of which probably reduce SS performance, are frequent. Little is known about the mechanisms maintaining such apparently suboptimal SSs. Here, we study the correlations between strengths of @entity2036 occupying different positions of the same SS. Such correlations may arise due to epistatic interactions between positions (i.e., a situation when the fitness effect of a @entity4334 in one position depends on the @entity4334 in another position), their evolutionary history, or to other reasons. Within both the intronic and the exonic parts of donor SSs, @entity2036 that increase (decrease) SS strength tend to co-occur with other @entity2036 increasing (respectively, decreasing) it, consistent with positive epistasis. Between the intronic and exonic parts of donor SSs, the correlations of @entity4334 strengths tend to be negative, consistent with negative epistasis. In the course of evolution, substitutions at a donor SS tend to decrease the strength of its exonic part, and either increase or do not change the strength of its intronic part. In acceptor SSs, the situation is more complicated; the correlations between adjacent positions appear to be driven mainly by avoidance of the AG dinucleotide which may cause aberrant splicing. In summary, both the content and the evolution of SSs is shaped by a complex network of interdependences between adjacent @entity2036 that respond to a range of sometimes conflicting selective constraints.
