Alternative Splicing: A Potential Source of Functional Innovation in the Eukaryotic Genome

Chen, Xuelan; Tovar-Corona, Jaime M.; Urrutia, Araxi O.

doi:10.1155/2012/596274

Cited by 70 publications

(60 citation statements)

References 96 publications

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“…These results are in principle consistent with an adaptive role of alternative splicing in determining a genome's functional information capacity and facilitating transcript diversification in species with greater numbers of cell types. It should be noted that some of the studies exploring changes in alternative splicing across evolutionary time and its association with cell-type diversification have not corrected for unequal transcript coverage between species (which distort estimates of alternative splicing [37][38][39]61,64]) leading to inconclusive results in some studies [61,64].…”

Section: Alternative Splicing Functional Innovation and The Evolutiomentioning

confidence: 99%

Alternative splicing and the evolution of phenotypic novelty

Bush

Chen

Tovar-Corona

et al. 2017

Phil. Trans. R. Soc. B

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168

122

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One contribution of 17 to a theme issue 'Evo-devo in the genomics era, and the origins of morphological diversity'. Alternative splicing, a mechanism of post-transcriptional RNA processing whereby a single gene can encode multiple distinct transcripts, has been proposed to underlie morphological innovations in multicellular organisms. Genes with developmental functions are enriched for alternative splicing events, suggestive of a contribution of alternative splicing to developmental programmes. The role of alternative splicing as a source of transcript diversification has previously been compared to that of gene duplication, with the relationship between the two extensively explored. Alternative splicing is reduced following gene duplication with the retention of duplicate copies higher for genes which were alternatively spliced prior to duplication. Furthermore, and unlike the case for overall gene number, the proportion of alternatively spliced genes has also increased in line with the evolutionary diversification of cell types, suggesting alternative splicing may contribute to the complexity of developmental programmes. Together these observations suggest a prominent role for alternative splicing as a source of functional innovation. However, it is unknown whether the proliferation of alternative splicing events indeed reflects a functional expansion of the transcriptome or instead results from weaker selection acting on larger species, which tend to have a higher number of cell types and lower population sizes.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.

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Section: Alternative Splicing Functional Innovation and The Evolutiomentioning

confidence: 99%

Alternative splicing and the evolution of phenotypic novelty

Bush

Chen

Tovar-Corona

et al. 2017

Phil. Trans. R. Soc. B

Self Cite

168

122

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“…It has been estimated that up to 95% of human multi-exon protein coding genes undergo alternative splicing, often in a tissue-or developmental stage-specific manner (13)(14)(15), and in response to external stimuli as part of several signal transduction networks (13,15). The generation of multiple distinct functional mRNA transcripts from a single gene, by one of the four major mechanisms of alternative splicing, is an important source of proteomic diversity, with critical roles in the control of developmental processes and in the dynamic regulation of the transcriptome (13,15,16).…”

Section: Discussionmentioning

confidence: 99%

“…The generation of multiple distinct functional mRNA transcripts from a single gene, by one of the four major mechanisms of alternative splicing, is an important source of proteomic diversity, with critical roles in the control of developmental processes and in the dynamic regulation of the transcriptome (13,15,16). Alternative splicing may have contributed to functional innovation during the evolution of the eukaryotic genome (14). The splicing process is performed by the spliceosome, a ribonucleoprotein megaparticle that assembles around splice sites at each intron (13,17).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism of RNA splicing is highly complex, requiring multiple interactions between premRNA, small nuclear ribonucleoproteins and a multitude of splicing factor proteins. Trans-acting factors, mainly RNA-binding proteins, modulate the activity of the spliceosome and of cis-acting RNA sequences, which include exonic and intronic splicing enhancers and silencers (13)(14)(15)17). In addition to their putative role in constitutive splicing, these cis-regulatory elements are also involved in the regulation of alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

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Individuals With Normal GLA Gene Sequence May Present Abnormally Spliced Alpha-Galactosidase mRNA Transcripts

Ferreira

Viana-Baptista

Rodrigues³

et al. 2015

Gene Cell Tissue

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Background: Deficient lysosomal α-galactosidase activity leads to intracellular accumulation of globotriaosylceramide (Gb3), which is the pathologic hallmark of Fabry disease (FD). There are over 750 pathogenic variants identified in the α-galactosidase gene (GLA). In rare patients, the cause of α-galactosidase deficiency is the overexpression of a GLA transcript with a cryptic exon in intron 4, which is physiologically present at trace levels. Objectives: We aim to report abnormally spliced alpha-galactosidase mRNA transcripts found with a cDNA-based GLA genotyping protocol performed in 482 patients. Patients and Methods: Genomic DNA and total RNA specimens were obtained from peripheral blood leukocytes of patients with premature stroke prospectively enrolled in the PORTYSTROKE study, or of patients with possible clinical manifestations of FD who have been referred for molecular diagnostic workup.Results: Approximately 20% of the patients expressed alternatively spliced transcripts of GLA mRNA involving exon 3. We additionally report that such non-canonical transcripts are physiologically expressed at trace levels in healthy individuals, and that their expression in leukocytes markedly increased in blood samples kept at room-temperature for 48 hours before RNA extraction. Conclusions: Production of alternatively spliced GLA transcripts might be involved in the regulation of GLA gene expression, and its deregulated overexpression, particularly if restricted to specific cells or tissues, might be the cause of organ-limited Gb3 pathology. Elucidation of the molecular mechanisms underlying the production of the non-canonical GLA transcripts warrants further investigation, as it may contribute important new data to the understanding of the molecular pathology of FD and Gb3-related disorders.

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“…However, the adaptive relevance of transcript diversification mediated by alternative splicing remains unclear [60,61].…”

Section: Recurring Themes (A) Genomic Changes Underlying Origins Of Mmentioning

confidence: 99%

Perspectives on the history of evo-devo and the contemporary research landscape in the genomics era

Tickle

Urrutia

2017

Phil. Trans. R. Soc. B

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A fundamental question in biology is how the extraordinary range of living organisms arose. In this theme issue, we celebrate how evolutionary studies on the origins of morphological diversity have changed over the past 350 years since the first publication of the Philosophical Transactions of The Royal Society . Current understanding of this topic is enriched by many disciplines, including anatomy, palaeontology, developmental biology, genetics and genomics. Development is central because it is the means by which genetic information of an organism is translated into morphology. The discovery of the genetic basis of development has revealed how changes in form can be inherited, leading to the emergence of the field known as evolutionary developmental biology (evo-devo). Recent approaches include imaging, quantitative morphometrics and, in particular, genomics, which brings a new dimension. Articles in this issue illustrate the contemporary evo-devo field by considering general principles emerging from genomics and how this and other approaches are applied to specific questions about the evolution of major transitions and innovations in morphology, diversification and modification of structures, intraspecific morphological variation and developmental plasticity. Current approaches enable a much broader range of organisms to be studied, thus building a better appreciation of the origins of morphological diversity. This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.

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Alternative Splicing: A Potential Source of Functional Innovation in the Eukaryotic Genome

Cited by 70 publications

References 96 publications

Alternative splicing and the evolution of phenotypic novelty

Alternative splicing and the evolution of phenotypic novelty

Individuals With Normal GLA Gene Sequence May Present Abnormally Spliced Alpha-Galactosidase mRNA Transcripts

Perspectives on the history of evo-devo and the contemporary research landscape in the genomics era

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