Rodent-specific alternative exons are more frequent in rapidly evolving genes and in paralogs

Ramil N Nurtdinov,Andrey A Mironov,Mikhail S Gelfand

doi:10.1186/1471-2148-9-142

Ramil N Nurtdinov, Andrey A Mironov + Show 1 more

Open Access

https://doi.org/10.1186/1471-2148-9-142

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Abstract

BackgroundAlternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes. Here, we studied the frequency and functionality of recently gained, rodent-specific alternative exons.ResultsWe projected the data about alternative splicing of mouse genes to the rat, human, and dog genomes, and identified exons conserved in the rat genome, but missing in more distant genomes. We estimated the frequency of rodent-specific exons while controlling for possible residual conservation of spurious exons. The frequency of rodent-specific exons is higher among predominantly skipped exons and exons disrupting the reading frame. Separation of all genes by the rate of sequence evolution and by gene families has demonstrated that rodent-specific cassette exons are more frequent in rapidly evolving genes and in rodent-specific paralogs.ConclusionThus we demonstrated that recently gained exons tend to occur in fast-evolving genes, and their inclusion rate tends to be lower than that of older exons. This agrees with the theory that gain of alternative exons is one of the major mechanisms of gene evolution.

Highlights

Alternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes
To avoid the influence of non-alignable genomes-specific exons, for this analysis we considered only orthologous exons
Several papers have showed that alternatively spliced regions evolve more rapidly compared to the constitutively spliced ones [[20,21], reviewed in [3]], but it substantially affects only minor isoform cassette exons [22]

Summary

Introduction

Alternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes. We studied the frequency and functionality of recently gained, rodent-specific alternative exons. Alternative splicing is one of the main mechanisms for generating functional and evolutionary diversity of proteins in mammals [1,2]. Initial comparative-genomic analyses of alternative splicing conservation have shown that the fraction of genome-specific alternative splicing may be as large as one fourth to one third of all observed alternatives [2,4,5] whereas recent estimates demonstrate that as much as 93% of human intron containing genes undergo alternative splicing [6,7]. In a study of conservation of human alternatively spliced genes in the mouse genome, we have demonstrated that conservation of cassette exons depends on their expression level (approximated by EST coverage) and their frame-preservation ability [8]. They still could (page number not for citation purposes)

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