The Evolutionary Landscape of Alternative Splicing in Vertebrate Species
Abstract
Whence Species Variation?: Vertebrates have widely varying phenotypes that are at odds with their much more limited proteincoding genotypes and conserved messenger RNA expression patterns. Genes with multiple exons and introns can undergo alternative splicing, potentially resulting in multiple protein isoforms (see the Perspective by Papasaikas and Valcárcel ). Barbosa-Morais et al. (p. 1587 ) and Merkin et al. (p. 1593 ) analyzed alternative splicing across the genomes of a variety of vertebrates, including human, primates, rodents, opossum, platypus, chicken, lizard, and frog. The findings suggest that the evolution of alternative splicing has for the most part been very rapid and that alternative splicing patterns of most organs more strongly reflect the identity of the species rather than the organ type. Species-classifying alternative splicing can affect key regulators, often in disordered regions of proteins that may influence protein-protein interactions, or in regions involved in protein phosphorylation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This regulatory versatility of alternative splicing has been implicated in the emergence of lineage-specific traits and in the evolution of brain complexity in primates.
“This regulatory versatility has been implicated in the emergence of lineage-specific traits and in the evolution of brain complexity in primates [42].”
From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [42]
Whole genome analyses brought a new appreciation of the pervasiveness and regulatory reach of alternative splicing in metazoan organisms.
“The advent of whole genome analyses10,12,188,189 brought a new appreciation of its pervasiveness and regulatory reach in metazoan organisms190,191.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [190]
Cites
Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
Saitou, N., & Nei, M. (1987) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040454 · Cited by 59,962 · see citing works
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849 · see citing works
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696 · see citing works
APE: Analyses of Phylogenetics and Evolution in R language
Paradis, E., Claude, J., & Strimmer, K. (2004) · Bioinformatics · doi:10.1093/bioinformatics/btg412 · Cited by 12,037 · see citing works
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,477 · see citing works
EMBOSS: the European molecular biology open software suite.
Rice, P., Longden, I., & Bleasby, A. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)02024-2 · Cited by 9,466 · see citing works
<tt>BLAT</tt> —The <tt>BLAST</tt> -Like Alignment Tool
Kent, W. J. (2002) · Genome Research · doi:10.1101/gr.229202 · Cited by 8,480 · see citing works
Pan, Q., Shai, O., Lee, L. J., Frey, B. J., & Blencowe, B. J. (2008) · Nature Genetics · doi:10.1038/ng.259 · Cited by 3,951 · see citing works
Self-citationGoecks, J., Nekrutenko, A., Taylor, J., & The Galaxy Team (2010) · Genome biology · doi:10.1186/gb-2010-11-8-r86 · Cited by 3,437 · see citing works
Diagnosis of multiple cancer types by shrunken centroids of gene expression
Tibshirani, R. J., Hastie, T. J., Narasimhan, B., & Chu, G. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082099299 · Cited by 2,938 · see citing works
The Spliceosome: Design Principles of a Dynamic RNP Machine
Wahl, M. C., Will, C. L., & Lührmann, R. (2009) · Cell · doi:10.1016/j.cell.2009.02.009 · Cited by 2,665 · see citing works
Galaxy: a platform for interactive large-scale genome analysis.Preprint
Giardine, B., Riemer, C., Hardison, R., Burhans, R. C., Elnitski, L., Shah, P., Zhang, Y., Blankenberg, D., Albert, I., Taylor, J., et al. (2005) · Genome Research · doi:10.1101/gr.4086505 · Cited by 2,217 · see citing works
TRANSFAC(R) and its module TRANSCompel(R): transcriptional gene regulation in eukaryotes
Matys, V. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj143 · Cited by 2,179 · see citing works
Expansion of the eukaryotic proteome by alternative splicing
Nilsen, T. W., & Graveley, B. R. (2010) · Nature · doi:10.1038/nature08909 · Cited by 2,172 · see citing works
Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing Signals
Yeo, G. W.-M., & Burge, C. B. (2004) · Journal of Computational Biology · doi:10.1089/1066527041410418 · Cited by 2,042 · see citing works
A molecular timescale for vertebrate evolution
Kumar, S., & Hedges, S. B. (1998) · Nature · doi:10.1038/31927 · Cited by 1,936 · see citing works
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays
Johnson, J. M., Castle, J. C., Garrett-Engele, P. W., Kan, Z., Loerch, P., Armour, C. D., Santos, R., Schadt, E. E., Stoughton, R. B., & Shoemaker, D. D. (2003) · Science · doi:10.1126/science.1090100 · Cited by 1,418 · see citing works
Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284 · see citing works
The evolution of gene expression levels in mammalian organs
Brawand, D., Soumillon, M., Necsulea, A., Julien, P., Csárdi, G., Harrigan, P., Weier, M., Liechti, A., Aximu-Petri, A., Kircher, M., et al. (2011) · Nature · doi:10.1038/nature10532 · Cited by 1,248 · see citing works
Cis-regulatory elements: Molecular mechanisms and evolutionary processes underlying divergence
Wittkopp, P. J., & Kalay, G. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3095 · Cited by 1,231 · see citing works
CDD: a Conserved Domain Database for protein classification
Marchler-Bauer, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki069 · Cited by 1,156 · see citing works
Alternative splicing and evolution: diversification, exon definition and function
Keren, H., Lev-Maor, G., & Ast, G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2776 · Cited by 1,082 · see citing works
Function and structure of inherently disordered proteins
Dunker, A. K., Silman, I., Uversky, V. N., & Sussman, J. L. (2008) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.10.002 · Cited by 963 · see citing works
Identification of novel transcripts in annotated genomes using RNA-Seq
Roberts, A., Pimentel, H., Trapnell, C., & Pachter, L. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr355 · Cited by 963 · see citing works
Transcriptome analysis by strand-specific sequencing of complementary DNA
Parkhomchuk, D., Borodina, T. A., Amstislavskiy, V. S., Banaru, M., Hallen, L., Krobitsch, S., Lehrach, H. R., & Солдатов, А. В. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp596 · Cited by 934 · see citing works
Barash, Y., Calarco, J. A., Gao, W., Pan, Q., Wang, X., Ofer Shai, A., Blencowe, B. J., & Frey, B. J. (2010) · Nature · doi:10.1038/nature09000 · Cited by 891 · see citing works
Self-citationFlicek, P., Amode, M. R., Barrell, D. G., Beal, K. M., Brent, S., Carvalho‐Silva, D., Clapham, P., Coates, G. M. P., Fairley, S., Fitzgerald, S. F., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr991 · Cited by 818 · see citing works
Self-citationRNA processing and its regulation: global insights into biological networks
Licatalosi, D. D., & Darnell, R. B. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2673 · Cited by 760 · see citing works
Functional consequences of developmentally regulated alternative splicing
Kalsotra, A., & Cooper, T. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3052 · Cited by 729 · see citing works
The DISOPRED server for the prediction of protein disorder
Ward, J. J., McGuffin, L. J., Bryson, K., Buxton, B. F., & Jones, D. T. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth195 · Cited by 684 · see citing works
RBPDB: a database of RNA-binding specificities
Cook, K. B., Kazan, H., Zuberi, K., Morris, Q., & Hughes, T. R. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1069 · Cited by 638 · see citing works
Variation in alternative splicing across human tissues
Yeo, G., Holste, D., Kreiman, G., & Burge, C. B. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r74 · Cited by 584 · see citing works
JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles
Portales-Casamar, É., Thongjuea, S., Kwon, A. T.-J., Arenillas, D. J., Zhao, X., Valen, E., Yusuf, D., Lenhard, B., Wasserman, W. W., & Sandelin, A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp950 · Cited by 574 · see citing works
Modrek, B., & Lee, C. J. (2003) · Nature Genetics · doi:10.1038/ng1159 · Cited by 523 · see citing works
A note on the neighbor-joining algorithm of Saitou and Nei.
Studier, J. A., & Keppler, K. J. (1988) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040527 · Cited by 445 · see citing works
The Birth of an Alternatively Spliced Exon: 3' Splice-Site Selection in Alu Exons
Lev-Maor, G., Sorek, R., Shomron, N., & Ast, G. (2003) · Science · doi:10.1126/science.1082588 · Cited by 435 · see citing works
An Aneuploid Mouse Strain Carrying Human Chromosome 21 with down Syndrome Phenotypes.
O'Doherty, A., Ruf, S., Mulligan, C., Hildreth, V., Errington, M. L., Cooke, S., Sesay, A., Modino, S., Vanes, L., Hernandez, D., et al. (2005) · Science · doi:10.1126/science.1114535 · Cited by 434 · see citing works
Tissue-specific alternative splicing remodels protein-protein interaction networks
Ellis, J. D., Barrios-Rodiles, M., Çolak, R., Irimia, M., Kim, T., Calarco, J. A., Wang, X., Pan, Q., O'Hanlon, D., Kim, P. M., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.037 · Cited by 431 · see citing works
Self-citationMicroRNAs and the advent of vertebrate morphological complexity
Heimberg, A. M., Sempere, L. F., Moy, V. N., Donoghue, P. C. J., & Peterson, K. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712259105 · Cited by 406 · see citing works
Buljan, M., Chalancon, G., Eustermann, S., Wagner, G. P., Fuxreiter, M., Bateman, A., & Babu, M. M. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.039 · Cited by 396 · see citing works
The UCSC Genome Browser database: extensions and updates 2011
Dreszer, T. R., Karolchik, D., Zweig, A. S., Hinrichs, A. S., Raney, B. J., Kuhn, R. M., Meyer, L. R., Wong, M., Sloan, C. A., Rosenbloom, K. R., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1055 · Cited by 349 · see citing works
Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A., Kalsotra, A., Cooper, T. A., & Johnson, J. M. (2008) · Nature Genetics · doi:10.1038/ng.264 · Cited by 319 · see citing works
Molecular and Genomic Data Identify the Closest Living Relative of Primates
Janečka, J. E., Miller, W., Pringle, T. H., Wiens, F., Zitzmann, A., Helgen, K. M., Springer, M. S., & Murphy, W. J. (2007) · Science · doi:10.1126/science.1147555 · Cited by 316 · see citing works
Identification and analysis of alternative splicing events conserved in human and mouse
Yeo, G. W.-M., Nostrand, E. L. V., Holste, D., Poggio, T., & Burge, C. B. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409742102 · Cited by 299 · see citing works
Species-Specific Transcription in Mice Carrying Human Chromosome 21
Wilson, M. D., Barbosa‐Morais, N. L., Schmidt, D., Conboy, C. B., Vanes, L., Tybulewicz, V. L. J., Fisher, E., Tavaré, S., & Odom, D. T. (2008) · Science · doi:10.1126/science.1160930 · Cited by 280 · see citing works
Self-citationHuman and mouse oligonucleotide-based array CGH
van den IJssel, P. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni191 · Cited by 274 · see citing works
Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats
Gracheva, E. O., Cordero-Morales, J. F., González‐Carcacía, J. A., Ingolia, N. T., Manno, C. D., Aranguren, C. I., Weissman, J. S., & Julius, D. J. (2011) · Nature · doi:10.1038/nature10245 · Cited by 260 · see citing works
The Genomic Record of Humankind's Evolutionary Roots
Goodman, M. (1999) · The American Journal of Human Genetics · doi:10.1086/302218 · Cited by 247 · see citing works
Conservation of an RNA regulatory map between Drosophila and mammalsPreprint
Brooks, A. N., Yang, L. C., Duff, M. O., Hansen, K. D., Park, J. W., Dudoit, S., Brenner, S. E., & Graveley, B. R. (2010) · Genome Research · doi:10.1101/gr.108662.110 · Cited by 236 · see citing works
Calarco, J. A., Superina, S., O'Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., et al. (2009) · Cell · doi:10.1016/j.cell.2009.06.012 · Cited by 225 · see citing works
Self-citationThe evolution of tribospheny and the antiquity of mammalian clades
Woodburne, M. O., Rich, T. H., & Springer, M. S. (2003) · Molecular Phylogenetics and Evolution · doi:10.1016/s1055-7903(03)00113-1 · Cited by 222 · see citing works
RESURRECTING THE ROLE OF TRANSCRIPTION FACTOR CHANGE IN DEVELOPMENTAL EVOLUTION
Lynch, V. J., & Wagner, G. P. (2008) · Evolution · doi:10.1111/j.1558-5646.2008.00440.x · Cited by 206 · see citing works
Regulation of alternative splicing by the core spliceosomal machineryPreprint
Saltzman, A. L., Pan, Q., & Blencowe, B. J. (2011) · Genes & Development · doi:10.1101/gad.2004811 · Cited by 204 · see citing works
Self-citationSaltzman, A. L., Kim, Y. K., Pan, Q., Fagnani, M. M., Maquat, L. E., & Blencowe, B. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00361-08 · Cited by 204 · see citing works
Self-citationTissue-specific splicing factor gene expression signatures
Grosso, A. R., Gomes, A. Q., Barbosa‐Morais, N. L., Caldeira, S., Thorne, N., Grech, G., Lindern, M. V., & Carmo‐Fonseca, M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn463 · Cited by 195 · see citing works
Self-citationConservation of core gene expression in vertebrate tissues
Chan, E. T., Quon, G. T., Chua, G., Babak, T., Trochesset, M., Zirngibl, R. A., Aubin, J., Ratcliffe, M. J., Wilde, A., Brudno, M., et al. (2009) · Journal of Biology · doi:10.1186/jbiol130 · Cited by 190 · see citing works
Alternative splicing: decoding an expansive regulatory layer
Irimia, M., & Blencowe, B. J. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.03.005 · Cited by 177 · see citing works
Self-citationBioMart Central Portal: an open database network for the biological community
Guberman, J. M., Ai, J., Arnaiz, O., Baran, J., Blake, A., Baldock, R., Chelala, C., Croft, D. W., Cros, A. F., Cutts, R. J., et al. (2011) · Database · doi:10.1093/database/bar041 · Cited by 164 · see citing works
Global analysis of alternative splicing differences between humans and chimpanzeesPreprint
Calarco, J. A., Xing, Y., Cáceres, M., Calarco, J. P., Xiao, X. G., Pan, Q., Lee, C. J., Preuss, T. M., & Blencowe, B. J. (2007) · Genes & Development · doi:10.1101/gad.1606907 · Cited by 158 · see citing works
Self-citationAlternative splicing of conserved exons is frequently species-specific in human and mouse
Pan, Q., Bakowski, M. A., Morris, Q., Zhang, W., Frey, B. J., Hughes, T. R., & Blencowe, B. J. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.12.004 · Cited by 149 · see citing works
Self-citationComparison of multiple vertebrate genomes reveals the birth and evolution of human exons
Zhang, X. H.-F., & Chasin, L. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603042103 · Cited by 138 · see citing works
Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB)
Wollerton, M., Gooding, C., Robinson, F., Brown, E. C., Jackson, R. J., & Smith, C. W. J. (2001) · RNA · doi:10.1017/s1355838201010214 · Cited by 132 · see citing works
Splicing factor and exon profiling across human tissues
de la Grange, P., Gratadou, L., Delord, M., Dutertre, M., & Auboeuf, D. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq008 · Cited by 127 · see citing works
Changes in exon–intron structure during vertebrate evolution affect the splicing pattern of exonsPreprint
Gelfman, S., Burstein, D. E., Penn, O., Savchenko, A., Amit, M., Schwartz, S., Pupko, T., & Ast, G. (2011) · Genome Research · doi:10.1101/gr.119834.110 · Cited by 109 · see citing works
The functional repertoires of metazoan genomes
Ponting, C. P. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2413 · Cited by 107 · see citing works
Barbosa‐Morais, N. L., Carmo‐Fonseca, M., & Aparicio, S. A. J. R. (2005) · Genome Research · doi:10.1101/gr.3936206 · Cited by 98 · see citing works
Self-citationBayesian prediction of tissue-regulated splicing using RNA sequence and cellular context
Xiong, H. Y., Barash, Y., & Frey, B. J. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr444 · Cited by 97 · see citing works
Self-citationEvolution of Nova-Dependent Splicing Regulation in the Brain
Jelen, N., Ule, J., Živin, M., & Darnell, R. B. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0030173 · Cited by 90 · see citing works
Comparative genomics of gene regulation—conservation and divergence of cis-regulatory information
Meireles-Filho, A. C. A., & Stark, A. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.10.006 · Cited by 80 · see citing works
Quantitative regulation of alternative splicing in evolution and development
Irimia, M., Rukov, J. L., Roy, S. W., Vinther, J., & García‐Fernàndez, J. (2009) · BioEssays · doi:10.1002/bies.080092 · Cited by 61 · see citing works
Self-citationTerai, Y., Morikawa, N., Kawakami, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2132833100 · Cited by 58 · see citing works
Estimation of alternative splicing variability in human populationsPreprint
Gonzàlez-Porta, M., Calvo, M., Sammeth, M., & Guigó, R. (2011) · Genome Research · doi:10.1101/gr.121947.111 · Cited by 55 · see citing works
RNA Processing: Redrawing the Map of Charted Territory
Corrionero, A., & Valcárcel, J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.12.004 · Cited by 15 · see citing works
An omics perspective of protein disorder
Bellay, J., Michaut, M., Kim, T. P., Han, S., Çolak, R., Myers, C. L., & Kim, P. M. (2011) · Molecular BioSystems · doi:10.1039/c1mb05235g · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062 · see citing works
Transcriptome and genome sequencing uncovers functional variation in humans
The Geuvadis Consortium, Lappalainen, T., Sammeth, M., Friedländer, M. R., ‘t Hoen, P. A. C., Monlong, J., Rivas, M. A., Gonzàlez-Porta, M., Kurbatova, N., Griebel, T., et al. (2013) · Nature · doi:10.1038/nature12531 · Cited by 1,888 · see citing works
A comparative encyclopedia of DNA elements in the mouse genome
Yue, F., Cheng, Y., Breschi, A., Vierstra, J., Wu, W., Ryba, T., Sandstrom, R., Ma, Z., Davis, C., Pope, B. D., et al. (2014) · Nature · doi:10.1038/nature13992 · Cited by 1,781 · see citing works
The human transcriptome across tissues and individuals
Melé, M., Ferreira, P. G., Reverter, F., DeLuca, D. S., Monlong, J., Sammeth, M., Young, T. R., Goldmann, J. M., Pervouchine, D. D., Sullivan, T. J., et al. (2015) · Science · doi:10.1126/science.aaa0355 · Cited by 1,304 · see citing works
Mechanisms and Regulation of Alternative Pre-mRNA Splicing
Lee, Y., & Rio, D. C. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034316 · Cited by 1,291 · see citing works
Intrinsically Disordered Proteins and Intrinsically Disordered Protein Regions
Oldfield, C. J., & Dunker, A. K. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-072711-164947 · Cited by 1,057 · see citing works
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044 · see citing works
Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878 · see citing works
Annotation-free quantification of RNA splicing using LeafCutter
Li, Y. I., Knowles, D. A., Humphrey, J., Barbeira, A. N., Dickinson, S. P., Im, H. K., & Pritchard, J. K. (2018) · Nature Genetics · doi:10.1038/s41588-017-0004-9 · Cited by 765 · see citing works
A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains
Irimia, M., Weatheritt, R. J., Ellis, J. D., Parikshak, N. N., Gonatopoulos-Pournatzis, T., Babor, M., Quesnel-Vallières, M., Tapial, J., Raj, B., O’Hanlon, D., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.035 · Cited by 693 · see citing works
“This is in marked contrast to the generally low degree of evolutionary conservation of other types of AS across vertebrate species (Barbosa-Morais et al., 2012; Braunschweig et al., 2014; Merkin et al., 2012).”
ResultSelf-citationWidespread intron retention in mammals functionally tunes transcriptomes
Braunschweig, U., Barbosa-Morais, N. L., Pan, Q., Nachman, E. N., Alipanahi, B., Gonatopoulos-Pournatzis, T., Frey, B., Irimia, M., & Blencowe, B. J. (2014) · Genome Research · doi:10.1101/gr.177790.114 · Cited by 664 · see citing works
Self-citationWidespread Expansion of Protein Interaction Capabilities by Alternative Splicing
Yang, X., Coulombe-Huntington, J., Kang, S., Sheynkman, G. M., Hao, T., Richardson, A., Sun, S., Yang, F., Shen, Y. A., Murray, R. R., et al. (2016) · Cell · doi:10.1016/j.cell.2016.01.029 · Cited by 583 · see citing works
Animal models of human disease: challenges in enabling translation
McGonigle, P., & Ruggeri, B. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.08.006 · Cited by 610 · see citing works
A new view of transcriptome complexity and regulation through the lens of local splicing variations
Vaquero-Garcia, J., Barrera, A., Gazzara, M. R., González-Vallinas, J., Lahens, N. F., Hogenesch, J. B., Lynch, K. W., & Barash, Y. (2016) · eLife · doi:10.7554/elife.11752 · Cited by 488 · see citing works
Landscape and variation of RNA secondary structure across the human transcriptome
Wan, Y., Qu, K., Zhang, Q. C., Flynn, R. A., Manor, O., Ouyang, Z., Zhang, J., Spitale, R. C., Snyder, M. P., Segal, E., et al. (2014) · Nature · doi:10.1038/nature12946 · Cited by 555 · see citing works
Raj, B., & Blencowe, B. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.004 · Cited by 475 · see citing works
Self-citationDynamic integration of splicing within gene regulatory pathways
Braunschweig, U., Gueroussov, S., Plocik, A. M., Graveley, B. R., & Blencowe, B. J. (2013) · Cell · doi:10.1016/j.cell.2013.02.034 · Cited by 406 · see citing works
Self-citationThe neurogenetics of alternative splicing
Vuong, C. K., Black, D. L., & Zheng, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.27 · Cited by 340 · see citing works
Georgilis, A., Klotz, S., Hanley, C. J., Herranz, N., Weirich, B., Morancho, B., Leote, A. C., D'Artista, L., Gallage, S., Seehawer, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.007 · Cited by 237 · see citing works
Self-citationSong, Y., Botvinnik, O. B., Lovci, M. T., Kakaradov, B., Liu, P., Xu, J. L., & Yeo, G. W. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.003 · Cited by 204 · see citing works
The ribosome-engaged landscape of alternative splicing
Weatheritt, R. J., Sterne-Weiler, T., & Blencowe, B. J. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3317 · Cited by 162 · see citing works
Self-citationEssential roles for the splicing regulator nSR100/SRRM4 during nervous system development
Quesnel-Vallières, M., Irimia, M., Cordes, S. P., & Blencowe, B. J. (2015) · Genes & Development · doi:10.1101/gad.256115.114 · Cited by 155 · see citing works
Self-citationvan den Hoogenhof (2016) · doi:10.1161/circresaha.115.307872 · Cited by 134 · see citing works
An alternative splicing event amplifies evolutionary differences between vertebrates
Gueroussov, S., Gonatopoulos-Pournatzis, T., Irimia, M., Raj, B., Lin, Z.-Y., Gingras, A.-C., & Blencowe, B. J. (2015) · Science · doi:10.1126/science.aaa8381 · Cited by 148 · see citing works
Self-citationA Global Regulatory Mechanism for Activating an Exon Network Required for Neurogenesis
Raj, B., Irimia, M., Braunschweig, U., Sterne-Weiler, T., O’Hanlon, D., Lin, Z.-Y., Chen, G. I., Easton, L. E., Ule, J., Gingras, A.-C., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.011 · Cited by 132 · see citing works
Self-citationBuilding Robust Transcriptomes with Master Splicing Factors
Jangi, M., & Sharp, P. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.054 · Cited by 141 · see citing works
Alternative pre-mRNA splicing in neurons: growing up and extending its reach
Zheng, S., & Black, D. L. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.04.003 · Cited by 115 · see citing works
Toffolo, E., Rusconi, F., Paganini, L., Tortorici, M., Pilotto, S., Heise, C., Verpelli, C., Tedeschi, G., Maffioli, E., Sala, C., et al. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12457 · Cited by 106 · see citing works
The circular RNome of primary breast cancer
Smid, M., Wilting, S. M., Uhr, K., Rodríguez-González, F. G., de Weerd, V., Prager-Van der Smissen, W. J. C., van der Vlugt-Daane, M., van Galen, A., Nik-Zainal, S., Butler, A., et al. (2019) · Genome Research · doi:10.1101/gr.238121.118 · Cited by 105 · see citing works
Intragenic epigenetic changes modulate NCAM alternative splicing in neuronal differentiation
Schor, I. E., Fiszbein, A., Petrillo, E., & Kornblihtt, A. R. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.167 · Cited by 90 · see citing works
Splice-Junction-Based Mapping of Alternative Isoforms in the Human Proteome
Lau, E., Han, Y., Williams, D. R., Thomas, C. T., Shrestha, R., Wu, J. C., & Lam, M. P. Y. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.026 · Cited by 67 · see citing works
Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease
On behalf of the European Early-Onset Dementia (EU EOD) consortium, De Roeck, A., Van den Bossche, T., van der Zee, J., Verheijen, J., De Coster, W., Van Dongen, J., Dillen, L., Baradaran-Heravi, Y., Heeman, B., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1714-x · Cited by 74 · see citing works
RNA-Seq Reveals Novel Transcriptional Reorganization in Human Alcoholic Brain
Farris, S. P., & Dayne Mayfield, R. (2014) · International Review of Neurobiology · doi:10.1016/b978-0-12-801105-8.00011-4 · Cited by 49 · see citing works
Microcephaly Modeling of Kinetochore Mutation Reveals a Brain-Specific Phenotype
Omer Javed, A., Li, Y., Muffat, J., Su, K.-C., Cohen, M. A., Lungjangwa, T., Aubourg, P., Cheeseman, I. M., & Jaenisch, R. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.032 · Cited by 46 · see citing works
Ghadie, M. A., Lambourne, L., Vidal, M., & Xia, Y. (2017) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1005717 · Cited by 39 · see citing works
Hao, Y., Colak, R., Teyra, J., Corbi-Verge, C., Ignatchenko, A., Hahne, H., Wilhelm, M., Kuster, B., Braun, P., Kaida, D., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.031 · Cited by 23 · see citing works
Self-citationRubin, B., & Anderson, S. (2017) · The Application of Clinical Genetics · doi:10.2147/tacg.s129638 · Cited by 21 · see citing works
Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications
Saccone, S., Brancato, D., Bruno, F., Coniglio, E., Sturiale, V., & Federico, C. (2025) · Genes · doi:10.3390/genes16060702 · Cited by 17 · see citing works
- Authors
- Barbosa-Morais, N. L., Irimia, M., Pan, Q., Xiong, H. Y., Gueroussov, S., Lee, L. J., Slobodeniuc, V., Kutter, C., Watt, S., Çolak, R., Kim, T., Misquitta-Ali, C. M., Wilson, M. D., Kim, P. M., Odom, D. T., Frey, B. J., & Blencowe, B. J.
- Affiliations
- Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
- University of Toronto (CA)
- University of Cambridge (GB)
- Corresponding author
- Irimia, Manuel
- Pan, Qun
- Xiong, Hui Y.
- Gueroussov, Serge
- Blencowe, Benjamin J.
- ORCID
- Venue
- Science
- Published
- 2012-12-21
- Volume
- 338
- Issue
- 6114
- Pages
- 1587-1593
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2151462466
- Cited by
- 1,063
- References
- 76
- Citations by year
- 2026: 56 · 2025: 74 · 2024: 86 · 2023: 56 · 2022: 67 · 2021: 100 · 2020: 76 · 2019: 75 · 2018: 84 · 2017: 85 · 2016: 89 · 2015: 87 · 2014: 74 · 2013: 52 · 2012: 2
- FWCI
- 27.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (15603, A15603)
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- alternative splicing, vertebrate evolution, phenotypic diversification, primates
- MeSH terms
- Animals, Chickens, Biological Evolution, Exons, Introns, Lizards, Mice, Inbred C57BL, Opossums, Phenotype, Platypus, Primates, Species Specificity, Vertebrates, Xenopus, Alternative Splicing, Evolution, Molecular, RNA Splice Sites, Regulatory Sequences, Ribonucleic Acid, Mice, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
