Alternative splicing and evolution: diversification, exon definition and function

  title={Alternative splicing and evolution: diversification, exon definition and function},
  author={Hadas Keren and Galit Lev-Maor and Gil Ast},
  journal={Nature Reviews Genetics},
Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals. Splicing can be found in species from bacteria to humans, but its prevalence and characteristics vary considerably. Evolutionary studies are helping to address questions that are fundamental to understanding this important process: how and when did AS evolve? Which AS events are functional? What are the evolutionary… 

Alternative splicing as a source of phenotypic diversity.

Although most splicing variants are probably non-functional, alternative splicing is nonetheless emerging as a dynamic, evolutionarily labile process that can facilitate adaptation and contribute to species divergence.

Inferring transcript phylogenies

The model and reconstruction algorithm is applied on two well-studied genes, MAG and PAX6, obtaining results consistent with current knowledge and thereby providing evidence that a phylogenetic analysis of transcripts is feasible and likely to be informative.

Lessons from non-canonical splicing

It is explained how non-canonical splicing can lead to aberrant transcripts that cause many diseases, and also how it can be exploited for new therapeutic strategies.

The importance of alternative splicing in adaptive evolution

This article discusses the contribution of standing splice variation to phenotypic plasticity and how hybridisation can produce novel splice forms, and proposes that alternative splicing be included as a standard analysis alongside gene expression analysis so to better understand of howAlternative splicing contributes to adaptive divergence at the micro‐ and macroevolutionary levels.

Alternative Splicing and Protein Diversity: Plants Versus Animals

A comprehensive summary of the current status of research in this area in both plants and humans is presented and the potential role of epigenetic modifications and chromatin state in splicing memory in plants primed with stresses is discussed.

Splicing in 4D

Part of the answer to the molecular mechanism by which the genome generates differences in organs between species relies on the broken syntax of genomic messages and uncovers striking differences in how evolution shapes the different layers of gene regulation.

Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution.

A Transcript Perspective on Evolution

A framework for transcript phylogenies where ancestral transcripts evolve along the gene tree by gains, losses, and mutation is presented and a new tool, TrEvoR, is developed and provided for this purpose.

Assessing the impact of alternative splicing on the diversity and evolution of the proteome in plants

Four bioinformatics studies aimed at determining the extent to which Alternative Splicing is used in plants as a mechanism for producing multiple distinct functional proteins from a single gene concluded that AS only has a limited impact on the functional diversity of the proteome in plants.

Functional consequences of developmentally regulated alternative splicing

Genome-wide analyses of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing, which can drive determinative physiological change or have a permissive role by providing mRNA variability that is used by other regulatory mechanisms.



How did alternative splicing evolve?

  • G. Ast
  • Biology
    Nature Reviews Genetics
  • 2004
The plasticity of the 5′ splice sites of multicellular eukaryotes means that these sites can be used in both constitutive and alternative splicing, and for the regulation of the inclusion/skipping ratio in alternativesplicing.

Common exon duplication in animals and its role in alternative splicing.

When searching the genomes of human, fly and worm for cases of exon duplication, it is found that about 10% of all genes contain tandemly duplicated exons, which indicates that it might have a significant role in the fast evolution of eukaryotic genes.

Alternative splicing and RNA selection pressure — evolutionary consequences for eukaryotic genomes

How alternative splicing has contributed to the evolution of modern genomes is considered, and constraints on evolution associated with alternative splice sites are discussed that might have important medical implications.

Alternative splicing: current perspectives

  • E. KimAmir GorenG. Ast
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2008
The current knowledge regarding issues from an evolutionary perspective of alternative splicing is summarized and the mechanisms by which multiple transcripts are generated from a single mRNA precursor are summarized.

Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches

Great progress has been made by studying individual transcripts and through genome-wide approaches, which together provide a better picture of the mechanistic regulation of alternative pre-mRNA splicing.

Low conservation of alternative splicing patterns in the human and mouse genomes.

It is demonstrated that about half of the analyzed genes have species-specific isoforms, and about a quarter of elementary alternatives are not conserved between the human and mouse genomes.

Differentiated evolutionary rates in alternative exons and the implications for splicing regulation

An analysis of the evolution of alternative and constitutive exons is performed, using a large set of protein coding exons conserved between human and mouse and taking into account the conservation of the transcript exonic structure, to conclude that most of the differences in dN observed between alternative and constitutional exons can be explained by the Conservation of the textural structure.

How prevalent is functional alternative splicing in the human genome?

Global analysis of exon creation versus loss and the role of alternative splicing in 17 vertebrate genomes.

The multigenome approach provides a comprehensive database of exon creation and loss events over 360 million years of vertebrate evolution, including tens of thousands of alternative and constitutive exons, and suggests that a large fraction of nonrepetitive created exons are results of ab initio creation from purely intronic sequences.