Alternative splicing and evolution: diversification, exon definition and function

Keren, Hadas; Lev-Maor, Galit; Ast, Gil

doi:10.1038/nrg2776

Cited by 942 publications

(866 citation statements)

References 121 publications

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“…This difference is likely the consequence of the relative contribution of gene duplication and alternative splicing to genome expansion in each lineage. Zebrafish have very high rates of gene duplication (Lu et al 2012) and display very low levels of alternative splicing (Lu et al 2010), while the inverse is true for humans (Shoja and Zhang 2006;Keren et al 2010). Therefore, it is not surprising that the effects of subfunctionalization will be amplified in a genomic background replete with alternative splicing yet relatively free of duplicate genes, as is the case with the human genome.…”

Section: Discussionmentioning

confidence: 99%

“…There are several types of alternative splicing events, including cassette exons, alternative 5 ′ and 3 ′ splice sites, mutually exclusive exons, and intron retention, with cassette exons being the most common in vertebrates. Interestingly, rates of alternative splicing correlate with organismal complexity, and it is alternative splicing that bridges the gap between the ∼22,000 genes within the human genome and the more than 100,000 unique proteins that the human genome codes for (Keren et al 2010). Given that both alternative splicing and gene duplication increase proteomic diversity, it is not surprising that several investigators have hypothesized that the two processes may be evolutionarily related.…”

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confidence: 99%

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Evidence for widespread subfunctionalization of splice forms in vertebrate genomes

et al. 2015

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Gene duplication and alternative splicing are important sources of proteomic diversity. Despite research indicating that gene duplication and alternative splicing are negatively correlated, the evolutionary relationship between the two remains unclear. One manner in which alternative splicing and gene duplication may be related is through the process of subfunctionalization, in which an alternatively spliced gene upon duplication divides distinct splice isoforms among the newly generated daughter genes, in this way reducing the number of alternatively spliced transcripts duplicate genes produce. Previously, it has been shown that splice form subfunctionalization will result in duplicate pairs with divergent exon structure when distinct isoforms become fixed in each paralog. However, the effects of exon structure divergence between paralogs have never before been studied on a genome-wide scale. Here, using genomic data from human, mouse, and zebrafish, we demonstrate that gene duplication followed by exon structure divergence between paralogs results in a significant reduction in levels of alternative splicing. In addition, by comparing the exon structure of zebrafish duplicates to the co-orthologous human gene, we have demonstrated that a considerable fraction of exon divergent duplicates maintain the structural signature of splice form subfunctionalization. Furthermore, we find that paralogs with divergent exon structure demonstrate reduced breadth of expression in a variety of tissues when compared to paralogs with identical exon structures and singletons. Taken together, our results are consistent with subfunctionalization partitioning alternatively spliced isoforms among duplicate genes and as such highlight the relationship between gene duplication and alternative splicing.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Evidence for widespread subfunctionalization of splice forms in vertebrate genomes

et al. 2015

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“…Two models explain the mechanism of exon and intron selection: intron definition and exon definition (Keren et al 2010). Placing the basal splicing machinery across introns is regarded as the ancient mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…3B,C). A specific set of histone modifications (including H2Bub1) may cause a well-defined ''exonic nucleosome'' during transcription elongation (Keren et al 2010). The more frequent occurrence of exon skipping in highly expressed genes (Fig.…”

Section: Specific H2bub1 Properties In Mammals Are Associated With Exmentioning

confidence: 99%

H2B monoubiquitylation is a 5′-enriched active transcription mark and correlates with exon–intron structure in human cells

Jung

Kim²,

Kim³

et al. 2012

Genome Res.

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H2B monoubiquitylation (H2Bub1), which is required for multiple methylations of both H3K4 and H3K79, has been implicated in gene expression in numerous organisms ranging from yeast to human. However, the molecular crosstalk between H2Bub1 and other modifications, especially the methylations of H3K4 and H3K79, remains unclear in vertebrates. To better understand the functional role of H2Bub1, we measured genome-wide histone modification patterns in human cells. Our results suggest that H2Bub1 has dual roles, one that is H3 methylation dependent, and another that is H3 methylation independent. First, H2Bub1 is a 59-enriched active transcription mark and co-occupies with H3K79 methylations in actively transcribed regions. Second, this study shows for the first time that H2Bub1 plays a histone H3 methylationsindependent role in chromatin architecture. Furthermore, the results of this work indicate that H2Bub1 is largely positioned at the exon-intron boundaries of highly expressed exons, and it demonstrates increased occupancy in skipped exons compared with flanking exons in the human and mouse genomes. Our findings collectively suggest that a potentiating mechanism links H2Bub1 to both H3K79 methylations in actively transcribed regions and the exon-intron structure of highly expressed exons via the regulation of nucleosome dynamics during transcription elongation.

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“…It is reported that this phenomenon take place in more than 90 % of the multiexons of H. sapiens [68]. Based on different splicing patterns, AS events can be categorized into several types: exon skipping, intron retention, mutually exclusive exon, alternative 5′ splice sites, alternative 3′ splice sites, alternative promoters, and alternative poly-A sites [69]. The process of alternative splicing is carried out by spliceosome and regulated through trans-acting factors and cis-acting sites [70].…”

Section: Alternative Splicing Of the P2x Genes In Vertebratementioning

confidence: 99%

Comparative study of the P2X gene family in animals and plants

Hou

Cao

2016

Purinergic Signalling

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P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while groupspecific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies.

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Alternative splicing and evolution: diversification, exon definition and function

Cited by 942 publications

References 121 publications

Evidence for widespread subfunctionalization of splice forms in vertebrate genomes

Evidence for widespread subfunctionalization of splice forms in vertebrate genomes

H2B monoubiquitylation is a 5′-enriched active transcription mark and correlates with exon–intron structure in human cells

Comparative study of the P2X gene family in animals and plants

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