Evolutionary Dynamics of Gene and Isoform Regulation in Mammalian Tissues

Overview

Journal Science

Specialty Science

Date 2012 Dec 22

PMID 23258891

Citations 542

Authors

Jason Merkin

Caitlin Russell

Ping Chen

Christopher B Burge

Affiliations

Soon will be listed here.

Abstract

Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.

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