Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes

Schwartz, Schraga; Silva, João; Burstein, David; Pupko, Tal; Eyras, Eduardo; Ast, Gil

doi:10.1101/gr.6818908

Cited by 168 publications

(209 citation statements)

References 74 publications

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“…The exon-intron structures of eukaryote genes vary across the eukaryotic kingdom, and the evolution of such structures increases in complexity from lower eukaryotes to higher eukaryotes. Our observations are largely consistent with and reinforce those reported previously with respect to introns and exons [9] [17] [22].…”

Section: Discussionsupporting

confidence: 93%

“…Comparative eukaryote genomics have suggested that intron evolution is a dynamic process in eukaryotes, and introns have been gained and lost in different genomes in response to strong selective pressures [8]. Although the basic ability of eukaryotes to splice introns is conserved, the splicing signals are evolved and shaped to different splicing mechanisms in diverse speciation [9] [10]. A comparative analysis of the basic splicing signals indicated that short intron recognition was rather susceptible to evolutionary changes in eukaryotes, but the overall pattern of intron recognition was well conserved in mammals [11].…”

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confidence: 99%

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Comparative Analysis of the Exon-Intron Structure in Eukaryotic Genomes

Li¹,

Xu²,

Ma³

2017

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The exon numbers and lengths vary in different eukaryotic species. With increasing completed genomic sequences, it is indispensable to reanalyze the gene organization in diverse eukaryotic genomes. We performed a large-scale comparative analysis of the exon-intron structure in 72 eukaryotic organisms, including plants, fungi and animals. We confirmed that the exon-intron structure varies massively among eukaryotic genomes and revealed some lineage-specific features of eukaryotic genes. These include a teleost-specific exon-intron structure pattern, relatively small introns and large exons in fungi and algae, and a gradual expansion of introns in vertebrates. Furthermore, the conservation analysis of exon-intron boundaries indicates that several bases near splice site junctions are different in introns with variable length among different species. After comparison, we identified a trend showing increases in intron densities and lengths in diverse species from fungi, plants, invertebrates to vertebrates, while it was the opposite in relation to exon lengths. The statistical properties of eukaryotic genomic organization suggest that genome-specific features are preserved by diverse evolutionary processes, which paves way for further research on the diversification of eukaryotic evolution.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Comparative Analysis of the Exon-Intron Structure in Eukaryotic Genomes

Li¹,

Xu²,

Ma³

2017

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“…4c; see below on SVA) 37,38 . In this gene, editing introduced an adenosine at the nucleotide upstream of the 5′-splice site, modifying the 5′-splice site from the consensus G|GT 39 to A|GT (| indicates the exon-intron boundary). Editing could thus have contributed to the weakening of the 5′-splice site.…”

Section: Identification Of Editing Sitesmentioning

confidence: 99%

Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

2011

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Retrotransposons had an important role in genome evolution, including the formation of new genes and promoters and the rewiring of gene networks. However, it is unclear how such a repertoire of functions emerged from a relatively limited number of source sequences. Here we show that DnA editing, an antiviral mechanism, accelerated the evolution of mammalian genomes by large-scale modification of their retrotransposon sequences. We find numerous pairs of retrotransposons containing long clusters of G-to-A mutations that cannot be attributed to random mutagenesis. These clusters, which we find across different mammalian genomes and retrotransposon families, are the hallmark of APoBEC3 activity, a potent antiretroviral protein family with cytidine deamination function. As DnA editing simultaneously generates a large number of mutations, each affected element begins its evolutionary trajectory from a unique starting point, thereby increasing the probability of developing a novel function. our findings thus suggest a potential mechanism for retrotransposon domestication.

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“…In contrast, exon skipping is far less prevalent in simpler eukaryotes (5,6); however, recent studies suggest that splicing in the last eukaryotic common ancestor was similar in many respects to splicing in vertebrates, in so much as it was intron-dense (7)(8)(9), had degenerate splice site sequences (10), and likely had many of the proteins involved in alternative splicing (11,12). Intron density correlates positively with the prevalence of alternative splicing across the eukaryotic kingdoms (13), and thus it has been posited that the intron-rich eukaryotic ancestor had alternative splicing, and may have had exon skipping.…”

mentioning

confidence: 99%

Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans

Awan

Manfredo

Pleiss

2013

Proc. Natl. Acad. Sci. U.S.A.

114

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Alternative splicing is a potent regulator of gene expression that vastly increases proteomic diversity in multicellular eukaryotes and is associated with organismal complexity. Although alternative splicing is widespread in vertebrates, little is known about the evolutionary origins of this process, in part because of the absence of phylogenetically conserved events that cross major eukaryotic clades. Here we describe a lariat-sequencing approach, which offers high sensitivity for detecting splicing events, and its application to the unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of the hallmarks of alternative splicing in mammalian systems but for which no previous examples of exon-skipping had been demonstrated. Over 200 previously unannotated splicing events were identified, including examples of regulated alternative splicing. Remarkably, an evolutionary analysis of four of the exons identified here as subject to skipping in S. pombe reveals high sequence conservation and perfect length conservation with their homologs in scores of plants, animals, and fungi. Moreover, alternative splicing of two of these exons have been documented in multiple vertebrate organisms, making these the first demonstrations of identical alternative-splicing patterns in species that are separated by over 1 billion y of evolution.pre-mRNA splicing | post-transcriptional gene regulation | phylogeny T he protein coding regions of eukaryotic genes are typically interrupted by noncoding introns that must be removed to produce a translatable mRNA. The removal of introns, catalyzed by the spliceosome, offers a powerful opportunity for an organism to regulate gene expression. In mammals, where individual genes are often interrupted by multiple introns, it is now abundantly clear that the process of intron removal provides a critical regulatory control point for both qualitative and quantitative aspects of gene expression (1). By changing the identity of the exons that are included within the final mRNA, the process of alternative splicing plays a critical role in expanding the diversity of proteins that can be synthesized within a cell (2). Moreover, alternative splicing can direct the production of isoforms of genes that are directly targeted to cellular decay pathways, providing a mechanism to quantitatively regulate gene expression (3, 4).In mammalian organisms the predominant form of alternative splicing is exon skipping, wherein different combinations of exons are included in the final transcript. In contrast, exon skipping is far less prevalent in simpler eukaryotes (5, 6); however, recent studies suggest that splicing in the last eukaryotic common ancestor was similar in many respects to splicing in vertebrates, in so much as it was intron-dense (7-9), had degenerate splice site sequences (10), and likely had many of the proteins involved in alternative splicing (11,12). Intron density correlates positively with the prevalence of alternative splicing across the eukaryotic kingdoms (13), and thus it has...

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Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes

Cited by 168 publications

References 74 publications

Comparative Analysis of the Exon-Intron Structure in Eukaryotic Genomes

Comparative Analysis of the Exon-Intron Structure in Eukaryotic Genomes

Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

Lariat sequencing in a unicellular yeast identifies regulated alternative splicing of exons that are evolutionarily conserved with humans

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