splicing and the evolution of proteins in mammals拼接和蛋白在哺乳动物的进化.pdf

PLoS BIOLOGY Splicing and the Evolution of Proteins in Mammals 1 1 2 2 1* Joanna L. Parmley , Araxi O. Urrutia , Lukasz Potrzebowski , Henrik Kaessmann , Laurence D. Hurst 1 Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom, 2 Center for Integrative Genomics, Genopode, University of Lausanne, Lausanne, Switzerland It is often supposed that a protein’s rate of evolution and its amino acid content are determined by the function and anatomy of the protein. Here we examine an alternative possibility, namely that the requirement to specify in the unprocessed RNA, in the vicinity of intron–exon boundaries, information necessary for removal of introns (e.g., exonic splice enhancers) affects both amino acid usage and rates of protein evolution. We find that the majority of amino acids show skewed usage near intron–exon boundaries, and that differences in the trends for the 2-fold and 4-fold blocks of both arginine and leucine show this to be owing to effects mediated at the nucleotide level. More specifically, there is a robust relationship between the extent to which an amino acid is preferred/avoided near boundaries and its enrichment/paucity in splice enhancers. As might then be expected, the rate of evolution is lowest near intron–exon boundaries, at least in part owing to splice enhancers, such that domains flanking intron–exon junctions evolve on average at under half the rate of exon centres from the same gene. In contrast, the rate of evolution of intronless retrogenes is highest near the domains where intron–exon junctions previously resided. The proportion of sequence near intron–exon boundaries is one