Evolutionary dynamics of U12-type spliceosomal introns

Chiao-Feng Lin,Artur Jarmołowski,Wojciech Makałowski,Stephen M Mount

doi:10.1186/1471-2148-10-47

Abstract

BackgroundMany multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.ResultsWe have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.ConclusionsAlthough complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.

Highlights

Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors
We found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported
To study the evolution of U12-type introns, we investigated conservation and changes of the intron state among U12-type introns and their orthologs in twenty sequenced eukaryotic genomes: Homo sapiens, Pan troglodytes, Macaca mulatta, Mus musculus, Rattus norvegicus, Canis familiaris, Bos taurus, Monodelphis domestica, Gallus gallus, Xenopus laevis, Fugu rubripes, Tetraodon nigroviridis, Danio rerio, Ciona intestinalis, Apis mellifera, Drosophila melanogaster, Anopheles gambiae, Caenorhabditis elegans, and Arabidopsis thaliana

Summary

Introduction

Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The removal of introns, in a process known as pre-mRNA splicing, is performed by the spliceosome, which consists of the U1, U2, U4, U5 and U6 snRNPs (small nuclear ribonucleoproteins), and more than 200 non-snRNP proteins [1,2,3]. Compilation of introns with non-consensus splice sites [7,8] led to the discovery of a minute class of introns. These introns contained an extended and nearly invariant 5’ splice site Dietrich et al [12] demonstrated that an AT-

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