Open AccessThe landscape of human mutually exclusive splicing
Author(s) -
Hatje Klas,
Rahman RazaUr,
Vidal Ramon O,
Simm Dominic,
Hammesfahr Björn,
Bansal Vikas,
Rajput Ashish,
Mickael Michel Edwar,
Sun Ting,
Bonn Stefan,
Kollmar Martin
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20177728
Subject(s) - biology , rna splicing , computational biology , genetics , evolutionary biology , gene , rna
Abstract Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons ( MXE s) using 515 publically available RNA ‐Seq datasets. Here, we provide evidence for the expression of over 855 MXE s, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi‐cluster MXE s in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila . Finally, MXE s are significantly enriched in pathogenic mutations and their spatio‐temporal expression might predict human disease pathology.