1932

Abstract

Animal species present relatively high levels of gene conservation, and yet they display a great variety of cell type and tissue phenotypes. These diverse phenotypes are mainly specified through differential gene usage, which relies on several mechanisms. Two of the most relevant mechanisms are regulated gene transcription, usually referred to as gene expression (rGE), and regulated alternative splicing (rAS). Several works have addressed how either rGE or rAS contributes to phenotypic diversity throughout evolution, but a back-to-back comparison between the two molecular mechanisms, specifically highlighting both their common regulatory principles and unique properties, is still missing. In this review, we propose an innovative framework for the unified comparison between rGE and rAS from different perspectives: the three-dimensional (3D)-evo space. We use the 3D-evo space to comprehensively () review the molecular basis of rGE and rAS (i.e., the molecular axis), () depict the tissue-specific phenotypes they contribute to (i.e., the tissue axis), and () describe the determinants that drive the evolution of rGE and rAS programs (i.e., the evolution axis). Finally, we unify the perspectives emerging from the three axes by discussing general trends and specific examples of rGE and rAS tissue program evolution.

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2022-11-30
2024-05-09
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Literature Cited

  1. 1.
    Arnoult L, Su KFY, Manoel D, Minervino C, Magriña J et al. 2013. Emergence and diversification of fly pigmentation through evolution of a gene regulatory module. Science 339:61261423–26
    [Google Scholar]
  2. 2.
    Barbosa-Morais NL, Irimia M, Pan Q, Xiong HY, Gueroussov S et al. 2012. The evolutionary landscape of alternative splicing in vertebrate species. Science 338:1587–93
    [Google Scholar]
  3. 3.
    Bebee TW, Park JW, Sheridan KI, Warzecha CC, Cieply BW et al. 2015. The splicing regulators Esrp1 and Esrp2 direct an epithelial splicing program essential for mammalian development. eLife 4:e08954
    [Google Scholar]
  4. 4.
    Berk AJ. 2016. Discovery of RNA splicing and genes in pieces. PNAS 113:4801–5
    [Google Scholar]
  5. 5.
    Berthelot C, Villar D, Horvath JE, Odom DT, Flicek P. 2018. Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression. Nat. Ecol. Evol. 2:1152–63
    [Google Scholar]
  6. 6.
    Boyle AP, Araya CL, Brdlik C, Cayting P, Cheng C et al. 2014. Comparative analysis of regulatory information and circuits across distant species. Nature 512:7515453–56
    [Google Scholar]
  7. 7.
    Brawand D, Soumillon M, Necsulea A, Julien P, Csárdi G et al. 2011. The evolution of gene expression levels in mammalian organs. Nature 478:7369343–48
    [Google Scholar]
  8. 8.
    Buckanovich RJ, Yang YY, Darnell RB. 1996. The onconeural antigen Nova-1 is a neuron-specific RNA-binding protein, the activity of which is inhibited by paraneoplastic antibodies. J. Neurosci. 16:31114–22
    [Google Scholar]
  9. 9.
    Burguera D, Marquez Y, Racioppi C, Permanyer J, Torres-Méndez A et al. 2017. Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes. Nat. Commun. 8:11799
    [Google Scholar]
  10. 10.
    Carelli FN, Liechti A, Halbert J, Warnefors M, Kaessmann H. 2018. Repurposing of promoters and enhancers during mammalian evolution. Nat. Commun. 9:14066
    [Google Scholar]
  11. 11.
    Chan ET, Quon GT, Chua G, Babak T, Trochesset M et al. 2009. Conservation of core gene expression in vertebrate tissues. J. Biol. 8:333
    [Google Scholar]
  12. 12.
    Chen J, Swofford R, Johnson J, Cummings BB, Rogel N et al. 2019. A quantitative framework for characterizing the evolutionary history of mammalian gene expression. Genome Res 29:153–63
    [Google Scholar]
  13. 13.
    Chen Z-F, Paquette AJ, Anderson DJ. 1998. NRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis. Nat. Genet. 20:2136–42
    [Google Scholar]
  14. 14.
    Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y et al. 1995. REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80:6949–57
    [Google Scholar]
  15. 15.
    Clarke SL, VanderMeer JE, Wenger AM, Schaar BT, Ahituv N, Bejerano G. 2012. Human developmental enhancers conserved between deuterostomes and protostomes. PLOS Genet 8:8e1002852
    [Google Scholar]
  16. 16.
    Cosby RL, Judd J, Zhang R, Zhong A, Garry N et al. 2021. Recurrent evolution of vertebrate transcription factors by transposase capture. Science 371:6531eabc6405
    [Google Scholar]
  17. 17.
    Csuros M, Rogozin IB, Koonin EV. 2011. A detailed history of intron-rich eukaryotic ancestors inferred from a global survey of 100 complete genomes. PLOS Comput. Biol. 7:9e1002150
    [Google Scholar]
  18. 18.
    de Crécy-Lagard V, Hanson AD 2013. Comparative genomics. Brenner's Encyclopedia of Genetics, Vol. 2 S Maloy, K Hughes 102–5 London: Academic. , 2nd ed..
    [Google Scholar]
  19. 19.
    Eom T, Zhang C, Wang H, Lay K, Fak J et al. 2013. NOVA-dependent regulation of cryptic NMD exons controls synaptic protein levels after seizure. eLife 2:e00178
    [Google Scholar]
  20. 20.
    Fagnani M, Barash Y, Ip JY, Misquitta C, Pan Q et al. 2007. Functional coordination of alternative splicing in the mammalian central nervous system. Genome Biol 8:6R108
    [Google Scholar]
  21. 21.
    Fernández R, Gabaldón T. 2020. Gene gain and loss across the metazoan tree of life. Nat. Ecol. Evol. 4:4524–33
    [Google Scholar]
  22. 22.
    Fortini ME, Skupski MP, Boguski MS, Hariharan IK. 2000. A survey of human disease gene counterparts in the Drosophila genome. J. Cell Biol. 150:2F23–30
    [Google Scholar]
  23. 23.
    Fu X-D, Ares M Jr. 2014. Context-dependent control of alternative splicing by RNA-binding proteins. Nat. Rev. Genet. 15:10689–701
    [Google Scholar]
  24. 24.
    Fukushima K, Pollock DD. 2020. Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution. Nat. Commun. 11:14459
    [Google Scholar]
  25. 25.
    Gelfman S, Burstein D, Penn O, Savchenko A, Amit M et al. 2012. Changes in exon–intron structure during vertebrate evolution affect the splicing pattern of exons. Genome Res 22:135–50
    [Google Scholar]
  26. 26.
    Giampietro C, Deflorian G, Gallo S, Di Matteo A, Pradella D et al. 2015. The alternative splicing factor Nova2 regulates vascular development and lumen formation. Nat. Commun. 6:8479
    [Google Scholar]
  27. 27.
    Gilbert W. 1978. Why genes in pieces?. Nature 271:5645501
    [Google Scholar]
  28. 28.
    Giudice J, Xia Z, Wang ET, Scavuzzo MA, Ward AJ et al. 2014. Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development. Nat. Commun. 5:3603
    [Google Scholar]
  29. 29.
    Grau-Bové X, Ruiz-Trillo I, Irimia M. 2018. Origin of exon skipping-rich transcriptomes in animals driven by evolution of gene architecture. Genome Biol 19:1135
    [Google Scholar]
  30. 30.
    Grosso AR, Gomes AQ, Barbosa-Morais NL, Caldeira S, Thorne NP et al. 2008. Tissue-specific splicing factor gene expression signatures. Nucleic Acids Res 36:154823–32
    [Google Scholar]
  31. 31.
    Gu X, Su Z. 2007. Tissue-driven hypothesis of genomic evolution and sequence-expression correlations. PNAS 104:82779–84
    [Google Scholar]
  32. 32.
    Guerreiro I, Nunes A, Woltering JM, Casaca A, Nóvoa A et al. 2013. Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine. PNAS 110:2610682–86
    [Google Scholar]
  33. 33.
    Guijarro-Clarke C, Holland PWH, Paps J. 2020. Widespread patterns of gene loss in the evolution of the animal kingdom. Nat. Ecol. Evol. 4:4519–23
    [Google Scholar]
  34. 34.
    Hamid FM, Makeyev EV. 2014. Emerging functions of alternative splicing coupled with nonsense-mediated decay. Biochem. Soc. Trans. 42:41168–73
    [Google Scholar]
  35. 35.
    Han H, Braunschweig U, Gonatopoulos-Pournatzis T, Weatheritt RJ, Hirsch CL et al. 2017. Multilayered control of alternative splicing regulatory networks by transcription factors. Mol. Cell 65:3539–53.e7
    [Google Scholar]
  36. 36.
    Han H, Irimia M, Ross PJ, Sung H-K, Alipanahi B et al. 2013. MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature 498:7453241–45
    [Google Scholar]
  37. 37.
    Hanson I, Van Heyningen V. 1995. Pax6: more than meets the eye. Trends Genet 11:7268–72
    [Google Scholar]
  38. 38.
    Heinz S, Romanoski CE, Benner C, Glass CK. 2015. The selection and function of cell type-specific enhancers. Nat. Rev. Mol. Cell Biol. 16:3144–54
    [Google Scholar]
  39. 39.
    Hill MS, Vande Zande P, Wittkopp PJ. 2021. Molecular and evolutionary processes generating variation in gene expression. Nat. Rev. Genet. 22:4203–15
    [Google Scholar]
  40. 40.
    Hu J, Qian H, Xue Y, Fu X-D. 2018. PTB/nPTB: master regulators of neuronal fate in mammals. Biophys. Rep. 4:4204–14
    [Google Scholar]
  41. 41.
    Irimia M, Denuc A, Burguera D, Somorjai I, Martín-Durán JM et al. 2011. Stepwise assembly of the Nova-regulated alternative splicing network in the vertebrate brain. PNAS 108:135319–24
    [Google Scholar]
  42. 42.
    Irimia M, Rukov JL, Penny D, Roy SW. 2007. Functional and evolutionary analysis of alternatively spliced genes is consistent with an early eukaryotic origin of alternative splicing. BMC Evol. Biol. 7:188
    [Google Scholar]
  43. 43.
    Irimia M, Rukov JL, Penny D, Vinther J, Garcia-Fernandez J, Roy SW. 2008. Origin of introns by “intronization” of exonic sequences. Trends Genet 24:8378–81
    [Google Scholar]
  44. 44.
    Irimia M, Weatheritt RJ, Ellis JD, Parikshak NN, Gonatopoulos-Pournatzis T et al. 2014. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 159:71511–23
    [Google Scholar]
  45. 45.
    Jelen N, Ule J, Živin M, Darnell RB. 2007. Evolution of Nova-dependent splicing regulation in the brain. PLOS Genet 3:10e173
    [Google Scholar]
  46. 46.
    Jensen KB, Dredge BK, Stefani G, Zhong R, Buckanovich RJ et al. 2000. Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron 25:2359–71
    [Google Scholar]
  47. 47.
    Katz LS, Gosmain Y, Marthinet E, Philippe J 2009. Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2. Mol. Cell. Biol. 29:82322–34
    [Google Scholar]
  48. 48.
    Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M et al. 2013. Function of alternative splicing. Gene 514:11–30
    [Google Scholar]
  49. 49.
    Keren H, Lev-Maor G, Ast G 2010. Alternative splicing and evolution: diversification, exon definition and function. Nat. Rev. Genet. 11:5345–55
    [Google Scholar]
  50. 50.
    Khor JM, Ettensohn CA. 2017. Functional divergence of paralogous transcription factors supported the evolution of biomineralization in echinoderms. eLife 6:e32728
    [Google Scholar]
  51. 51.
    King M-C, Wilson AC. 1975. Evolution at two levels in humans and chimpanzees. Science 188:4184107–16
    [Google Scholar]
  52. 52.
    Koonin EV. 2006. The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate?. Biol. Direct 1:22
    [Google Scholar]
  53. 53.
    Kosti I, Radivojac P, Mandel-Gutfreund Y. 2012. An integrated regulatory network reveals pervasive cross-regulation among transcription and splicing factors. PLOS Comput. Biol. 8:7e1002603
    [Google Scholar]
  54. 54.
    Kwan CW, Gavin-Smyth J, Ferguson EL, Schmidt-Ott U. 2016. Functional evolution of a morphogenetic gradient. eLife 5:e20894
    [Google Scholar]
  55. 55.
    Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y et al. 2018. The human transcription factors. Cell 172:4650–65
    [Google Scholar]
  56. 56.
    Lambert SA, Yang AWH, Sasse A, Cowley G, Albu M et al. 2019. Similarity regression predicts evolution of transcription factor sequence specificity. Nat. Genet. 51:6981–89
    [Google Scholar]
  57. 57.
    Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:6822860–921
    [Google Scholar]
  58. 58.
    Lev-Maor G, Sorek R, Shomron N, Ast G. 2003. The birth of an alternatively spliced exon: 3'splice-site selection in Alu exons. Science 300:56231288–91
    [Google Scholar]
  59. 59.
    Liang C, Musser JM, Cloutier A, Prum RO, Wagner GP. 2018. Pervasive correlated evolution in gene expression shapes cell and tissue type transcriptomes. Genome Biol. Evol. 10:2538–52
    [Google Scholar]
  60. 60.
    Liao B-Y, Zhang J. 2006. Low rates of expression profile divergence in highly expressed genes and tissue-specific genes during mammalian evolution. Mol. Biol. Evol. 23:61119–28
    [Google Scholar]
  61. 61.
    Licatalosi DD, Mele A, Fak JJ, Ule J, Kayikci M et al. 2008. HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 456:7221464–69
    [Google Scholar]
  62. 62.
    Lien S, Koop BF, Sandve SR, Miller JR, Kent MP et al. 2016. The Atlantic salmon genome provides insights into rediploidization. Nature 533:7602200–5
    [Google Scholar]
  63. 63.
    Lin S, Fu X-D. 2007. SR proteins and related factors in alternative splicing. Adv. Exp. Med. Biol. 623:107–22
    [Google Scholar]
  64. 64.
    Linares AJ, Lin C-H, Damianov A, Adams KL, Novitch BG, Black DL. 2015. The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation. eLife 4:e09268
    [Google Scholar]
  65. 65.
    Ling JP, Chhabra R, Merran JD, Schaughency PM, Wheelan SJ et al. 2016. PTBP1 and PTBP2 repress nonconserved cryptic exons. Cell Rep 17:1104–13
    [Google Scholar]
  66. 66.
    Louis EJ. 2007. Making the most of redundancy. Nature 449:7163673–74
    [Google Scholar]
  67. 67.
    Lynch VJ, Leclerc RD, May G, Wagner GP 2011. Transposon-mediated rewiring of gene regulatory networks contributed to the evolution of pregnancy in mammals. Nat. Genet. 43:111154–59
    [Google Scholar]
  68. 68.
    Ma J. 2005. Crossing the line between activation and repression. Trends Genet 21:154–59
    [Google Scholar]
  69. 69.
    Marlétaz F, Firbas PN, Maeso I, Tena JJ, Bogdanovic O et al. 2018. Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature 564:773464–70
    [Google Scholar]
  70. 70.
    Marnetto D, Mantica F, Molineris I, Grassi E, Pesando I, Provero P. 2018. Evolutionary rewiring of human regulatory networks by waves of genome expansion. Am. J. Hum. Genet. 102:2207–18
    [Google Scholar]
  71. 71.
    Márquez Y, Mantica F, Cozzuto L, Burguera D, Hermoso-Pulido A et al. 2021. ExOrthist: a tool to infer exon orthologies at any evolutionary distance. Genome Biol 22:1239
    [Google Scholar]
  72. 72.
    Martín G, Márquez Y, Mantica F, Duque P, Irimia M. 2021. Alternative splicing landscapes in Arabidopsis thaliana across tissues and stress conditions highlight major functional differences with animals. Genome Biol 22:135
    [Google Scholar]
  73. 73.
    Martinez-Contreras R, Cloutier P, Shkreta L, Fisette J-F, Revil T, Chabot B. 2007. hnRNP proteins and splicing control. Adv. Exp. Med. Biol. 623:123–47
    [Google Scholar]
  74. 74.
    Maston GA, Evans SK, Green MR. 2006. Transcriptional regulatory elements in the human genome. Annu. Rev. Genom. Hum. Genet. 7:29–59
    [Google Scholar]
  75. 75.
    Melé M, Ferreira PG, Reverter F, DeLuca DS, Monlong J et al. 2015. The human transcriptome across tissues and individuals. Science 348:6235660–65
    [Google Scholar]
  76. 76.
    Merkin J, Russell C, Chen P, Burge CB 2012. Evolutionary dynamics of gene and isoform regulation in mammalian tissues. Science 338:61141593–99
    [Google Scholar]
  77. 77.
    Miyawaki S, Kuroki S, Maeda R, Okashita N, Koopman P, Tachibana M. 2020. The mouse Sry locus harbors a cryptic exon that is essential for male sex determination. Science 370:6512121–24
    [Google Scholar]
  78. 78.
    Modrek B, Lee CJ. 2003. Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nat. Genet. 34:2177–80
    [Google Scholar]
  79. 79.
    Moore MJ, Wang Q, Kennedy CJ, Silver PA. 2010. An alternative splicing network links cell-cycle control to apoptosis. Cell 142:4625–36
    [Google Scholar]
  80. 80.
    Nadimpalli S, Persikov AV, Singh M. 2015. Pervasive variation of transcription factor orthologs contributes to regulatory network evolution. PLOS Genet 11:3e1005011
    [Google Scholar]
  81. 81.
    Nakano Y, Wiechert S, Bánfi B. 2019. Overlapping activities of two neuronal splicing factors switch the GABA effect from excitatory to inhibitory by regulating REST. Cell Rep 27:3860–71.e8
    [Google Scholar]
  82. 82.
    Nitta KR, Jolma A, Yin Y, Morgunova E, Kivioja T et al. 2015. Conservation of transcription factor binding specificities across 600 million years of bilateria evolution. eLife 4:e04837
    [Google Scholar]
  83. 83.
    Nurtdinov RN, Artamonova II, Mironov AA, Gelfand MS. 2003. Low conservation of alternative splicing patterns in the human and mouse genomes. Hum. Mol. Genet. 12:111313–20
    [Google Scholar]
  84. 84.
    Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW et al. 2007. Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat. Genet. 39:6730–32
    [Google Scholar]
  85. 85.
    Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR et al. 2011. Induction of human neuronal cells by defined transcription factors. Nature 476:7359220–23
    [Google Scholar]
  86. 86.
    Paps J, Holland PWH. 2018. Reconstruction of the ancestral metazoan genome reveals an increase in genomic novelty. Nat. Commun. 9:11730
    [Google Scholar]
  87. 87.
    Park JW, Yang J, Xu R-H. 2018. PAX6 alternative splicing and corneal development. Stem Cells Dev 27:6367–77
    [Google Scholar]
  88. 88.
    Parras A, Anta H, Santos-Galindo M, Swarup V, Elorza A et al. 2018. Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing. Nature 560:7719441–46
    [Google Scholar]
  89. 89.
    Quesnel-Vallières M, Dargaei Z, Irimia M, Gonatopoulos-Pournatzis T, Ip JY et al. 2016. Misregulation of an activity-dependent splicing network as a common mechanism underlying autism spectrum disorders. Mol. Cell 64:61023–34
    [Google Scholar]
  90. 90.
    Quesnel-Vallières M, Irimia M, Cordes SP, Blencowe BJ. 2015. Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development. Genes Dev 29:7746–59
    [Google Scholar]
  91. 91.
    Raposo AASF, Vasconcelos FF, Drechsel D, Marie C, Johnston C et al. 2015. Ascl1 coordinately regulates gene expression and the chromatin landscape during neurogenesis. Cell Rep 10:91544–56
    [Google Scholar]
  92. 92.
    Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS et al. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature 499:7457172–77
    [Google Scholar]
  93. 93.
    Reyes A, Anders S, Weatheritt RJ, Gibson TJ, Steinmetz LM, Huber W. 2013. Drift and conservation of differential exon usage across tissues in primate species. PNAS 110:3815377–82
    [Google Scholar]
  94. 94.
    Rogozin IB, Babenko VN, Fedorova ND, Jackson JD, Jacobs AR et al. 2003. Evolution of eukaryotic gene repertoire and gene structure: discovering the unexpected dynamics of genome evolution. Cold Spring Harb. Symp. Quant. Biol. 68:293–301
    [Google Scholar]
  95. 95.
    Roller M, Stamper E, Villar D, Izuogu O, Martin F et al. 2021. LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions. Genome Biol 22:162
    [Google Scholar]
  96. 96.
    Romero IG, Ruvinsky I, Gilad Y. 2012. Comparative studies of gene expression and the evolution of gene regulation. Nat. Rev. Genet. 13:7505–16
    [Google Scholar]
  97. 97.
    Roy SW, Gilbert W. 2005. Complex early genes. PNAS 102:61986–91
    [Google Scholar]
  98. 98.
    Royo JL, Maeso I, Irimia M, Gao F, Peter IS et al. 2011. Transphyletic conservation of developmental regulatory state in animal evolution. PNAS 108:3414186–91
    [Google Scholar]
  99. 99.
    Saito Y, Yuan Y, Zucker-Scharff I, Fak JJ, Jereb S et al. 2019. Differential NOVA2-mediated splicing in excitatory and inhibitory neurons regulates cortical development and cerebellar function. Neuron 101:4707–20.e5
    [Google Scholar]
  100. 100.
    Sander M, Neubüser A, Kalamaras J, Ee HC, Martin GR, German MS. 1997. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11:131662–73
    [Google Scholar]
  101. 101.
    Schmidt D, Schwalie PC, Wilson MD, Ballester B, Gonçalves A et al. 2012. Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. Cell 148:1–2335–48
    [Google Scholar]
  102. 102.
    Shirai LT, Saenko SV, Keller RA, Jerónimo MA, Brakefield PM et al. 2012. Evolutionary history of the recruitment of conserved developmental genes in association to the formation and diversification of a novel trait. BMC Evol. Biol. 12:21
    [Google Scholar]
  103. 103.
    Simpson TI, Price DJ. 2002. Pax6; a pleiotropic player in development. Bioessays 24:111041–51
    [Google Scholar]
  104. 104.
    Singh P, Ahi EP. 2022. The importance of alternative splicing in adaptive evolution. Mol. Ecol. 31:71928–38
    [Google Scholar]
  105. 105.
    Sorek R, Ast G, Graur D. 2002. Alu-containing exons are alternatively spliced. Genome Res 12:71060–67
    [Google Scholar]
  106. 106.
    Soutourina J. 2018. Transcription regulation by the Mediator complex. Nat. Rev. Mol. Cell Biol. 19:4262–74
    [Google Scholar]
  107. 107.
    Spitz F, Furlong EEM. 2012. Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13:9613–26
    [Google Scholar]
  108. 108.
    St-Onge L, Sosa-Pineda B, Chowdhury K, Mansouri A, Gruss P. 1997. Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas. Nature 387:6631406–9
    [Google Scholar]
  109. 109.
    Sucena E, Delon I, Jones I, Payre F, Stern DL. 2003. Regulatory evolution of shavenbaby/ovo underlies multiple cases of morphological parallelism. Nature 424:6951935–38
    [Google Scholar]
  110. 110.
    Sucena E, Stern DL. 2000. Divergence of larval morphology between Drosophila sechellia and its sibling species caused by cis-regulatory evolution of ovo/shaven-baby. PNAS 97:94530–34
    [Google Scholar]
  111. 111.
    Sudmant PH, Alexis MS, Burge CB. 2015. Meta-analysis of RNA-seq expression data across species, tissues and studies. Genome Biol 16:287
    [Google Scholar]
  112. 112.
    Swisa A, Avrahami D, Eden N, Zhang J, Feleke E et al. 2017. PAX6 maintains β cell identity by repressing genes of alternative islet cell types. J. Clin. Investig. 127:1230–43
    [Google Scholar]
  113. 113.
    Taliaferro JM, Alvarez N, Green RE, Blanchette M, Rio DC. 2011. Evolution of a tissue-specific splicing network. Genes Dev 25:6608–20
    [Google Scholar]
  114. 114.
    Tan Q, Yalamanchili HK, Park J, De Maio A, Lu H-C et al. 2016. Extensive cryptic splicing upon loss of RBM17 and TDP43 in neurodegeneration models. Hum. Mol. Genet. 25:235083–93
    [Google Scholar]
  115. 115.
    Tapial J, Ha KCH, Sterne-Weiler T, Gohr A, Braunschweig U et al. 2017. An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms. Genome Res 27:101759–68
    [Google Scholar]
  116. 116.
    Tennant BR, Robertson AG, Kramer M, Li L, Zhang X et al. 2013. Identification and analysis of murine pancreatic islet enhancers. Diabetologia 56:3542–52
    [Google Scholar]
  117. 117.
    Thakurela S, Tiwari N, Schick S, Garding A, Ivanek R et al. 2016. Mapping gene regulatory circuitry of Pax6 during neurogenesis. Cell Discov. 2:15045
    [Google Scholar]
  118. 118.
    Thanaraj TA, Clark F, Muilu J 2003. Conservation of human alternative splice events in mouse. Nucleic Acids Res 31:102544–52
    [Google Scholar]
  119. 119.
    Torres-Méndez A, Bonnal S, Marquez Y, Roth J, Iglesias M et al. 2019. A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nat. Ecol. Evol. 3:4691–701
    [Google Scholar]
  120. 120.
    Torres-Méndez A, Pop S, Bonnal S, Almudi I, Avola A et al. 2022. Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals. Sci. Adv. 8:4eabk0445
    [Google Scholar]
  121. 121.
    Tress ML, Abascal F, Valencia A. 2017. Alternative splicing may not be the key to proteome complexity. Trends Biochem. Sci. 42:298–110
    [Google Scholar]
  122. 122.
    Ule J, Blencowe BJ. 2019. Alternative splicing regulatory networks: functions, mechanisms, and evolution. Mol. Cell 76:2329–45
    [Google Scholar]
  123. 123.
    Ule J, Stefani G, Mele A, Ruggiu M, Wang X et al. 2006. An RNA map predicting Nova-dependent splicing regulation. Nature 444:7119580–86
    [Google Scholar]
  124. 124.
    Venter JC, Adams MD, Myers EW, Li PW. 2001. The sequence of the human genome. Science 291:55071304–51
    [Google Scholar]
  125. 125.
    Verta J-P, Jacobs A. 2021. The role of alternative splicing in adaptation and evolution. Trends Ecol. Evol. 37:4299–308
    [Google Scholar]
  126. 126.
    Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M. 2010. Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463:72841035–41
    [Google Scholar]
  127. 127.
    Villar D, Berthelot C, Aldridge S, Rayner TF, Lukk M et al. 2015. Enhancer evolution across 20 mammalian species. Cell 160:3554–66
    [Google Scholar]
  128. 128.
    Villate O, Turatsinze J-V, Mascali LG, Grieco FA, Nogueira TC et al. 2014. Nova1 is a master regulator of alternative splicing in pancreatic beta cells. Nucleic Acids Res 42:1811818–30
    [Google Scholar]
  129. 129.
    Waks Z, Klein AM, Silver PA. 2011. Cell-to-cell variability of alternative RNA splicing. Mol. Syst. Biol. 7:506
    [Google Scholar]
  130. 130.
    Warzecha CC, Shen S, Xing Y, Carstens RP. 2009. The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events. RNA Biol 6:5546–62
    [Google Scholar]
  131. 131.
    Witten JT, Ule J. 2011. Understanding splicing regulation through RNA splicing maps. Trends Genet 27:389–97
    [Google Scholar]
  132. 132.
    Yang YY, Yin GL, Darnell RB. 1998. The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. PNAS 95:2213254–59
    [Google Scholar]
  133. 133.
    Zattara EE, Busey HA, Linz DM, Tomoyasu Y, Moczek AP. 2016. Neofunctionalization of embryonic head patterning genes facilitates the positioning of novel traits on the dorsal head of adult beetles. Proc. R. Soc. B 283:20160824
    [Google Scholar]
  134. 134.
    Zhang C, Frias MA, Mele A, Ruggiu M, Eom T et al. 2010. Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls. Science 329:5990439–43
    [Google Scholar]
  135. 135.
    Zhang C, Zhang Z, Castle J, Sun S, Johnson J et al. 2008. Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev 22:182550–63
    [Google Scholar]
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