Positive selection in alternatively spliced exons of human genes

Alternative splicing is a well-recognized mechanism of accelerated genome evolution. We have studied single-nucleotide polymorphisms and human-chimpanzee divergence in the exons of 6672 alternatively spliced human genes, with the aim of understanding the forces driving the evolution of alternatively spliced sequences. Here, we show that alternatively spliced exons and exon fragments (alternative exons) from minor isoforms experience lower selective pressure at the amino acid level, accompanied by selection against synonymous sequence variation. The results of the McDonald-Kreitman test suggest that alternatively spliced exons, unlike exons constitutively included in the mRNA, are also subject to positive selection, with up to 27% of amino acids fixed by positive selection.     

Identification and cDNA sequence of delta-preprotachykinin, a fourth splicing variant of the rat substance P precursor.

The neuropeptides substance P and neurokinin A are synthesised from a family of precursor polypeptides encoded by the preprotachykinin A (PPT) gene. In addition to a mRNA (beta-PPT) containing all 7 exons of the gene, alternatively spliced mRNAs lacking either exon 4 (gamma-PPT) or exon 6 (alpha-PPT) have been identified. We have determined the sequences of cDNA clones encoding four variants of PPT mRNA from rat dorsal root ganglion (DRG), including a novel mRNA species (delta-PPT) in which both exons 4 and 6 are absent. The sequence of delta-PPT predicts the existence of a novel tachykinin precursor polypeptide.