Comparison of splice sites in mammals and chicken

Abstract

We have carried out an initial analysis of the dynamics of the recent evolution of the splice-sites sequences on a large collection of human, rodent (mouse and rat), and chicken introns. Our results indicate that the sequences of splice sites are largely homogeneous within tetrapoda. We have also found that orthologous splice signals between human and rodents and within rodents are more conserved than unrelated splice sites, but the additional conservation can be explained mostly by background intron conservation. In contrast, additional conservation over background is detectable in orthologous mammalian and chicken splice sites. Our results also indicate that the U2 and U12 intron classes seem to have evolved independently since the split of mammals and birds; we have not been able to find a convincing case of interconversion between these two classes in our collections of orthologous introns. Similarly, we have not found a single case of switching between AT-AC and GT-AG subtypes within U12 introns, suggesting that this event has been a rare occurrence in recent evolutionary times. Switching between GT-AG and the noncanonical GC-AG U2 subtypes, on the contrary, does not appear to be unusual; in particular, T to C mutations appear to be relatively well tolerated in GT-AG introns with very strong donor sites.

Figure 1.

Donor and acceptor sites' pictograms. Pictograms of the donor (left) and the acceptor (right) site sequences for the U2 (top) and U12 (bottom) splice sites. The sequence plots for GT-AG and GC-AG U2 introns are given separately. The conserved sequence of the U12 branch point is also shown. From human, mouse, rat, and chicken RefSeq genes, a total number of 337,336, 2506, and 935 splice-site sequences from CDS introns from Ensembl were included in GT-AG, GC-AG, and U12 splice site sets, respectively, to produce the corresponding pictograms.

Figure 2.

Comparative pictograms for donor and acceptor splice sites. Comparative pictograms of donor and acceptor sites for pairwise comparisons between species at different phylogenetic distances. At each position, the nucleotide distribution of the two species is displayed, the height of the letters corresponding to their relative frequency at the position. The color in the background of the letters indicates the underrepresentation (green) or overrepresentation (red) of a given nucleotide in the second species (right) with respect to the first (left).

Figure 3.

Sequence conservation level of orthologous GT-AG splice sites. Shaded gray areas correspond to the typical sequence span of splice-site signals. The average identity between the orthologous sequences is plotted across the splice signals (see Discussion). Background identity has been estimated from pairs of nonorthologous sites. (Bottom) The result of subtracting background conservation from total conservation.