Evolution of new exons and alternative splicing in primates

Abstract

New exons are frequently created within existing genes during the evolution of eukaryotic genomes. Based on mRNA and EST data, the vast majority of newly created exons are spliced only at very low levels. Thus, new exons have been generally considered as evolutionary intermediates that lack established functions. In this study, using a large‐scale genomic and molecular analysis of new exons derived from retrotransposons, we provided genomic evidence for the evolutionary significance of widespread exon creation during primate and human evolution. Contrary to the common belief that strong splicing activities of new exons result exclusively from disease mutations, we identified newly born exons constitutively spliced in a broad range of human tissues, as well as exons with tissue‐specific splicing. In a related study, we found hundreds of genes with human‐specific splicing events in the brain transcriptome. Some of these events modulate protein domains critical for protein‐protein interactions; others affect transcripts previously implicated in brain diseases. Together, our studies reveal substantial changes in exon usage and splicing patterns during human evolution, suggesting that alternative splicing played a central role in the acquisition of human‐specific traits.Supported by the NIH (YX), Edward Mallinckrodt Jr. Foundation (YX), Roy J. Carver Trust (BLD).