title: Origins and impacts of new mammalian exons.
abstract: Mammalian genes are composed of exons, but the evolutionary origins and functions of new internal exons are poorly understood. Here, we analyzed patterns of exon gain using deep cDNA sequencing data from five mammals and one bird, identifying thousands of species- and lineage-specific exons. Most new exons derived from unique rather than repetitive intronic sequence. Unlike exons conserved across mammals, species-specific internal exons were mostly located in 5' UTRs and alternatively spliced. They were associated with upstream intronic deletions, increased nucleosome occupancy, and RNA polymerase II pausing. Genes containing new internal exons had increased gene expression, but only in tissues in which the exon was included. Increased expression correlated with the level of exon inclusion, promoter proximity, and signatures of cotranscriptional splicing. Altogether, these findings suggest that increased splicing at the 5' ends of genes enhances expression and that changes in 5' end splicing alter gene expression between tissues and between species.
authors: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Jason J
authors: JJ
authors: Merkin
authors: Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, University of Helsinki, 00014 Helsinki, Finland.
authors: Ping
authors: P
authors: Chen
authors: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors: Maria S
authors: MS
authors: Alexis
authors: Research Programs Unit, Genome-Scale Biology and Institute of Biomedicine, University of Helsinki, 00014 Helsinki, Finland.
authors: Sampsa K
authors: SK
authors: Hautaniemi
authors: Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: cburge@mit.edu.
authors: Christopher B
authors: CB
authors: Burge
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001717:Birds / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D007438:Introns; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D017384:Sequence Deletion