How did alternative splicing evolve?

Ast, Gil

doi:10.1038/nrg1451

Cited by 504 publications

(507 citation statements)

References 76 publications

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“…In many ways, this is similar to the role of neofunctionalisation of recent duplicate loci in the generation of evolutionary novelty (Lynch and Conery, 2000). The widespread incidence of alternative splicing in plasticity, gene function and adaptation is starting to be understood, but how this will contribute to adaptive divergence and ultimately speciation is only beginning to be explored (Ast, 2004;Harr and Turner, 2010).…”

Section: Discussionmentioning

confidence: 99%

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

et al. 2013

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There has been much debate concerning whether cis-regulatory or coding changes are more likely to produce evolutionary innovation or adaptation in gene function, but an additional complication is that some genes can dramatically diverge through alternative splicing, increasing the diversity of gene function within a locus. The fruitless gene is a major transcription factor with a wide range of pleiotropic functions, including a fundamental conserved role in sexual differentiation, species-specific morphology and an important influence on male sexual behaviour. Here, we examine the structure of fruitless in multiple species of Drosophila, and determine the patterns of selective constraint acting across the coding region. We found that the pattern of selection, estimated from the ratio of non-synonymous to synonymous substitutions, varied considerably across the gene, with most regions of the gene evolutionarily conserved but with several regions showing evidence of divergence as a result of positive selection. The regions that showed evidence of positive selection were found to be localised to relatively consistent regions across multiple speciation events, and are associated with alternative splicing. Alternative splicing may thus provide a route to gene diversification in key regulatory loci.

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Section: Discussionmentioning

confidence: 99%

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

et al. 2013

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“…22 Control and regulation of alternative splicing is not completely understood. 23 Expression of CD44v isoforms is under the control of mitogenic signals including the Ras-MAP kinase cascade. 24 The mechanism(s) through which CD44v isoforms block Fas-mediated apoptosis has so far never been described.…”

Section: Introductionmentioning

confidence: 99%

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

et al. 2005

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There is growing evidence that one of the central common characteristics of tumor and inflammatory cells is their resistance to programmed cell death. This feature results in the accumulation of harmful cells, which are mostly refractory to Fas (FAS, APO-1)-mediated apoptosis. A molecule found on these cells is the transmembrane receptor CD44 with its variant isoforms (CD44v). The establishment of transfectants expressing different CD44v isoforms allowed us to demonstrate that the CD44v6 and CD44v9 isoforms exhibit an antiapoptotic effect and can block Fas-mediated apoptosis. Moreover, we observed that CD44v6 and CD44v9 colocalize and interact with Fas. Importantly, an anti-CD44v6 antibody can abolish the antiapoptotic effect of CD44v6. These results are the first to show that CD44v isoforms interfere with Fas signaling. Our findings improve the understanding of the pathogenesis of cancer and autoimmunity and open new strategies to treat such disorders.

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“…230 Alternative splicing can modulate organism complexity, not only by effectively increasing proteome size and regulatory and signaling network complexity, but also by doing so in a time-and tissue-specific manner, supporting cell differentiation, developmental pathways, and other processes associated with multicellular organisms. 231 Recently we have shown that a large majority (~80%) of alternatively spliced fragments in a set of experimentally characterized proteins is associated with fully or partially disordered regions. This suggests that polypeptide segments affected by alternative splicing are most often intrinsically disordered.…”

Section: Intrinsic Disorder and Coding Sequence Diversitymentioning

confidence: 99%

Functional Anthology of Intrinsic Disorder. 2. Cellular Components, Domains, Technical Terms, Developmental Processes, and Coding Sequence Diversities Correlated with Long Disordered Regions

et al. 2007

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Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

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How did alternative splicing evolve?

Cited by 504 publications

References 76 publications

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

A novel antiapoptotic mechanism based on interference of Fas signaling by CD44 variant isoforms

Functional Anthology of Intrinsic Disorder. 2. Cellular Components, Domains, Technical Terms, Developmental Processes, and Coding Sequence Diversities Correlated with Long Disordered Regions

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