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Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence


To explore the phylogenetic limits of conservation of cis-regulatory elements, we used transgenesis to test the functions of enhancers of four genes from several species spanning the phylum Nematoda. While we found a striking degree of functional conservation among the examined cis elements, their DNA sequences lacked apparent conservation with the C. elegans orthologs. In fact, sequence similarity between C. elegans and the distantly related nematodes was no greater than would be expected by chance. Short motifs, similar to known regulatory sequences in C. elegans, can be detected in most of the cis elements. When tested, some of these sites appear to mediate regulatory function. However, they seem to have originated through motif turnover, rather than to have been preserved from a common ancestor. Our results suggest that gene regulatory networks are broadly conserved in the phylum Nematoda, but this conservation persists despite substantial reorganization of regulatory elements and could not be detected using naïve comparisons of sequence similarity.


Vyšlo v časopise: Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005268
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005268

Souhrn

To explore the phylogenetic limits of conservation of cis-regulatory elements, we used transgenesis to test the functions of enhancers of four genes from several species spanning the phylum Nematoda. While we found a striking degree of functional conservation among the examined cis elements, their DNA sequences lacked apparent conservation with the C. elegans orthologs. In fact, sequence similarity between C. elegans and the distantly related nematodes was no greater than would be expected by chance. Short motifs, similar to known regulatory sequences in C. elegans, can be detected in most of the cis elements. When tested, some of these sites appear to mediate regulatory function. However, they seem to have originated through motif turnover, rather than to have been preserved from a common ancestor. Our results suggest that gene regulatory networks are broadly conserved in the phylum Nematoda, but this conservation persists despite substantial reorganization of regulatory elements and could not be detected using naïve comparisons of sequence similarity.


Zdroje

1. Slack JMW, Holland PWH, Graham CF (1993) The Zootype and the Phylotypic Stage. Nature 361: 490–492. 8094230

2. Panganiban G, Irvine SM, Lowe C, Roehl H, Corley LS, et al. (1997) The origin and evolution of animal appendages. Proc Natl Acad Sci U S A 94: 5162–5166. 9144208

3. Holley SA, Jackson PD, Sasai Y, Lu B, De Robertis EM, et al. (1995) A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature 376: 249–253. 7617035

4. Gehring WJ (2005) New perspectives on eye development and the evolution of eyes and photoreceptors. J Hered 96: 171–184. 15653558

5. Fukushige T, Brodigan TM, Schriefer LA, Waterston RH, Krause M (2006) Defining the transcriptional redundancy of early bodywall muscle development in C. elegans: evidence for a unified theory of animal muscle development. Genes Dev 20: 3395–3406. 17142668

6. Carroll SB (2008) Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 134: 25–36. doi: 10.1016/j.cell.2008.06.030 18614008

7. Takahashi H, Mitani Y, Satoh G, Satoh N (1999) Evolutionary alterations of the minimal promoter for notochord-specific Brachyury expression in ascidian embryos. Development 126: 3725–3734. 10433903

8. Oda-Ishii I, Bertrand V, Matsuo I, Lemaire P, Saiga H (2005) Making very similar embryos with divergent genomes: conservation of regulatory mechanisms of Otx between the ascidians Halocynthia roretzi and Ciona intestinalis. Development 132: 1663–1674. 15743880

9. True JR, Haag ES (2001) Developmental system drift and flexibility in evolutionary trajectories. Evol Dev 3: 109–119. 11341673

10. Hinman VF, Davidson EH (2007) Evolutionary plasticity of developmental gene regulatory network architecture. Proc Natl Acad Sci U S A 104: 19404–19409. 18042699

11. Rebeiz M, Stone T, Posakony JW (2005) An ancient transcriptional regulatory linkage. Dev Biol 281: 299–308. 15893980

12. Goltsev Y, Hsiong W, Lanzaro G, Levine M (2004) Different combinations of gap repressors for common stripes in Anopheles and Drosophila embryos. Dev Biol 275: 435–446. 15501229

13. Gordon KL, Ruvinsky I (2012) Tempo and Mode in Evolution of Transcriptional Regulation. Plos Genet 8: e1002432–e1002432. doi: 10.1371/journal.pgen.1002432 22291600

14. Guastella J, Johnson CD, Stretton AOW (1991) Gaba-Immunoreactive Neurons in the Nematode Ascaris. J Comp Neurol 307: 584–597. 1869633

15. Johnson C, Stretton A (1987) GABA-immunoreactivity in inhibitory motor neurons of the nematode Ascaris. J Neurosci 7: 223–235. 3543249

16. Voronov D, Panchin Y (1998) Cell lineage in marine nematode Enoplus brevis. Development 125: 143–150. 9389672

17. Wiegner O, Schierenberg E (1999) Regulative development in a nematode embryo: a hierarchy of cell fate transformations. Dev Biol 215: 1–12. 10525346

18. Goldstein B (2001) On the evolution of early development in the Nematoda. Philos Trans R Soc Lond B Biol Sci 356: 1521–1531. 11604120

19. Schulze J, Schierenberg E (2011) Evolution of embryonic development in nematodes. Evodevo 2: 18. doi: 10.1186/2041-9139-2-18 21929824

20. Kiontke K, Barrière A, Kolotuev I, Podbilewicz B, Sommer R, et al. (2007) Trends, stasis, and drift in the evolution of nematode vulva development. Curr Biol 17: 1925–1937. 18024125

21. Hill RC, de Carvalho CE, Salogiannis J, Schlager B, Pilgrim D, et al. (2006) Genetic flexibility in the convergent evolution of hermaphroditism in Caenorhabditis nematodes. Dev Cell 10: 531–538. 16580997

22. Wang X, Chamberlin HM (2004) Evolutionary innovation of the excretory system in Caenorhabditis elegans. Nat Genet 36: 231–232. 14758362

23. Verster AJ, Ramani AK, McKay SJ, Fraser AG (2014) Comparative RNAi screens in C. elegans and C. briggsae reveal the impact of developmental system drift on gene function. PLoS Genet 10: e1004077. doi: 10.1371/journal.pgen.1004077 24516395

24. Rota-Stabelli O, Daley AC, Pisani D (2013) Molecular timetrees reveal a Cambrian colonization of land and a new scenario for ecdysozoan evolution. Curr Biol 23: 392–398. doi: 10.1016/j.cub.2013.01.026 23375891

25. Blaxter M (2011) Nematodes: The Worm and Its Relatives. PLoS Biol 9: e1001050. doi: 10.1371/journal.pbio.1001050 21526226

26. The C. elegans Sequencing Consortium (1998) Genome Sequence of the Nematode C. elegans: A Platform for Investigating Biology. Science 282: 2012–2018. 9851916

27. Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, et al. (2003) The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol 1: E45. 14624247

28. Abad P, Gouzy J, Aury J-M, Castagnone-Sereno P, Danchin EGJ, et al. (2008) Genome sequence of the metazoan plant-parasitic nematode Meloidogyne incognita. Nat Biotechnol 26: 909–915. doi: 10.1038/nbt.1482 18660804

29. Opperman CH, Bird DM, Williamson VM, Rokhsar DS, Burke M, et al. (2008) Sequence and genetic map of Meloidogyne hapla: A compact nematode genome for plant parasitism. Proc Natl Acad Sci U S A 105: 14802–14807. doi: 10.1073/pnas.0805946105 18809916

30. Blaxter M, Daub J, Guiliano D, Parkinson J, Whitton C (2002) The Brugia malayi genome project: expressed sequence tags and gene discovery. Trans R Soc Trop Med Hyg 96: 7–17. 11925998

31. Ghedin E, Wang S, Spiro D, Caler E, Zhao Q, et al. (2007) Draft genome of the filarial nematode parasite Brugia malayi. Science 317: 1756–1760. 17885136

32. Mitreva M, Jasmer DP, Zarlenga DS, Wang Z, Abubucker S, et al. (2011) The draft genome of the parasitic nematode Trichinella spiralis. Nat Genet 43: 228–235. doi: 10.1038/ng.769 21336279

33. McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389: 870–876. 9349821

34. McIntire SL, Jorgensen E, Horvitz HR (1993) Genes required for GABA function in Caenorhabditis elegans. Nature 364: 334–337. 8332190

35. Jin Y, Jorgensen E, Hartwieg E, Horvitz HR (1999) The Caenorhabditis elegans Gene unc-25 Encodes Glutamic Acid Decarboxylase and Is Required for Synaptic Transmission But Not Synaptic Development. J Neurosci 19: 539–548. 9880574

36. Barriere A, Gordon KL, Ruvinsky I (2011) Distinct Functional Constraints Partition Sequence Conservation in a cis-Regulatory Element. PLoS Genet 7: e1002095. doi: 10.1371/journal.pgen.1002095 21655084

37. Barrière A, Gordon KL, Ruvinsky I (2012) Coevolution within and between regulatory loci can preserve promoter function despite evolutionary rate acceleration. PLoS Genet 8: e1002961. doi: 10.1371/journal.pgen.1002961 23028368

38. Barrière A, Ruvinsky I (2014) Pervasive Divergence of Transcriptional Gene Regulation in Caenorhabditis Nematodes. PLoS Genet 10: e1004435. doi: 10.1371/journal.pgen.1004435 24968346

39. Ruvinsky I, Ruvkun G (2003) Functional tests of enhancer conservation between distantly related species. Development 130: 5133–5142. 12944426

40. Way JC, Chalfie M (1988) mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell 54: 5–16. 2898300

41. Way JC, Chalfie M (1989) The mec-3 gene of Caenorhabditis elegans requires its own product for maintained expression and is expressed in three neuronal cell types. Genes Dev 3: 1823–1833. 2576011

42. Xue D, Finney M, Ruvkun G, Chalfie M (1992) Regulation of the mec-3 gene by the C.elegans homeoproteins UNC-86 and MEC-3. EMBO J 11: 4969–4979. 1361171

43. Fukushige T, Hawkins MG, McGhee JD (1998) The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine. Dev Biol 198: 286–302. 9659934

44. Hawkins MG, McGhee JD (1995) elt-2, a Second GATA Factor from the Nematode Caenorhabditis elegans. J Biol Chem 270: 14666–14671. 7782329

45. Gilleard JS (2004) The use of Caenorhabditis elegans in parasitic nematode research. Parasitology 128: S49–S70. 16454899

46. McGhee JD (2012) The Caenorhabditis elegans intestine. Wiley Interdiscip Rev Dev Biol 2: 347–367. doi: 10.1002/wdev.93 23799580

47. Eastman C, Horvitz HR, Jin YS (1999) Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the Caenorhabditis elegans UNC-90 homeodomain protein. J Neurosci 19: 6225–6234. 10414952

48. Rebeiz M, Castro B, Liu F, Yue F, Posakony JW (2012) Ancestral and conserved cis-regulatory architectures in developmental control genes. Dev Biol 362: 282–294. doi: 10.1016/j.ydbio.2011.12.011 22185795

49. Navratilova P, Fredman D, Hawkins TA, Turner K, Lenhard B, et al. (2009) Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes. Dev Biol 327: 526–540. doi: 10.1016/j.ydbio.2008.10.044 19073165

50. Blanco J, Girard F, Kamachi Y, Kondoh H, Gehring WJ (2005) Functional analysis of the chicken delta1-crystallin enhancer activity in Drosophila reveals remarkable evolutionary conservation between chicken and fly. Development 132: 1895–1905. 15790965

51. Brugger SM, Merrill AE, Torres-Vazquez J, Wu N, Ting M-C, et al. (2004) A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development 131: 5153–5165. 15459107

52. Clarke SL, VanderMeer JE, Wenger AM, Schaar BT, Ahituv N, et al. (2012) Human developmental enhancers conserved between deuterostomes and protostomes. PLoS Genet 8: e1002852. doi: 10.1371/journal.pgen.1002852 22876195

53. Shimeld SM, Purkiss AG, Dirks RPH, Bateman O a, Slingsby C, et al. (2005) Urochordate betagamma-crystallin and the evolutionary origin of the vertebrate eye lens. Curr Biol 15: 1684–1689. 16169492

54. Xu PX, Zhang X, Heaney S, Yoon a, Michelson a M, et al. (1999) Regulation of Pax6 expression is conserved between mice and flies. Development 126: 383–395. 9847251

55. Royo JL, Maeso I, Irimia M, Gao F, Peter IS, et al. (2011) Transphyletic conservation of developmental regulatory state in animal evolution. Proc Natl Acad Sci U S A 108: 14186–14191. doi: 10.1073/pnas.1109037108 21844364

56. Ayyar S, Negre B, Simpson P, Stollewerk A (2010) An arthropod cis-regulatory element functioning in sensory organ precursor development dates back to the Cambrian. BMC Biol 8: 127. doi: 10.1186/1741-7007-8-127 20868489

57. Locascio A, Aniello F, Amoroso A, Manzanares M, Krumlauf R, et al. (1999) Patterning the ascidian nervous system: structure, expression and transgenic analysis of the CiHox3 gene. Development 126: 4737–4748. 10518491

58. Arnone M, Davidson E (1997) The hardwiring of development: organization and function of genomic regulatory systems. Development 124: 1851–1864. 9169833

59. Wray GA, Hahn MW, Abouheif E, Balhoff JP, Pizer M, et al. (2003) The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20: 1377–1419. 12777501

60. Kimura-Yoshida C, Kitajima K, Oda-Ishii I, Tian E, Suzuki M, et al. (2004) Characterization of the pufferfish Otx2 cis-regulators reveals evolutionarily conserved genetic mechanisms for vertebrate head specification. Development 131: 57–71. 14645121

61. Stern DL (2000) Perspective: Evolutionary developmental biology and the problem of variation. Evolution (N Y) 54: 1079–1091.

62. He Z, Eichel K, Ruvinsky I (2011) Functional Conservation of Cis-Regulatory Elements of Heat-Shock Genes over Long Evolutionary Distances. PLoS One 6: e22677. doi: 10.1371/journal.pone.0022677 21799932

63. Franks RR, Hough-Evans BR, Britten RJ, Davidson EH (1988) Spatially deranged though temporally correct expression of Strongylocentrotus purpuratus actin gene fusion in transgenic embryos of a different sea urchin family. Genes Dev 2: 1–12. 3162723

64. Cooper GM, Brown CD (2008) Qualifying the relationship between sequence conservation and molecular function. Genome Res 18: 201–205. doi: 10.1101/gr.7205808 18245453

65. Dutilh BE, Huynen MA, Snel B (2006) A global definition of expression context is conserved between orthologs, but does not correlate with sequence conservation. BMC Genomics 7: 10. 16423292

66. Fisher S, Grice EA, Vinton RM, Bessling SL, McCallion AS (2006) Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312: 276–279. 16556802

67. McGaughey DM, Vinton RM, Huynh J, Al-Saif A, Beer MA, et al. (2008) Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b. Genome Res 18: 252–260. 18071029

68. Nelson AC, Wardle FC (2013) Conserved non-coding elements and cis regulation: actions speak louder than words. Development 140: 1385–1395. doi: 10.1242/dev.084459 23482485

69. Taher L, McGaughey DM, Maragh S, Aneas I, Bessling SL, et al. (2011) Genome-wide identification of conserved regulatory function in diverged sequences. Genome Res 21: 1139–1149. doi: 10.1101/gr.119016.110 21628450

70. Erives A, Levine M (2004) Coordinate enhancers share common organizational features in the Drosophila genome. Proc Natl Acad Sci U S A 101: 3851–3856. 15026577

71. Aparicio S, Morrison A, Gould A, Gilthorpe J, Chaudhuri C, et al. (1995) Detecting Conserved Regulatory Elements with the Model Genome of the Japanese Puffer Fish, Fugu Rubripes. Proc Natl Acad Sci U S A 92: 1684–1688. 7878040

72. Hinman VF, Nguyen AT, Cameron RA, Davidson EH (2003) Developmental gene regulatory network architecture across 500 million years of echinoderm evolution. Proc Natl Acad Sci U S A 100: 13356–13361. 14595011

73. Stern DL, Orgogozo V (2008) The loci of evolution: How predictable is genetic evolution? Evolution (N Y) 62: 2155–2177. doi: 10.1111/j.1558-5646.2008.00450.x 18616572

74. Bullaughey K (2011) Changes in Selective Effects Over Time Facilitate Turnover of Enhancer Sequences. Genetics 187: 567–U328. doi: 10.1534/genetics.110.121590 21098721

75. He BZ, Holloway AK, Maerkl SJ, Kreitman M (2011) Does Positive Selection Drive Transcription Factor Binding Site Turnover? A Test with Drosophila Cis-Regulatory Modules. Plos Genet 7: e1002053. doi: 10.1371/journal.pgen.1002053 21572512

76. Brown CD, Johnson DS, Sidow A (2007) Functional architecture and evolution of transcriptional elements that drive gene coexpression. Science 317: 1557–1560. 17872446

77. Liberman LM, Stathopoulos A (2009) Design flexibility in cis-regulatory control of gene expression: synthetic and comparative evidence. Dev Biol 327: 578–589. doi: 10.1016/j.ydbio.2008.12.020 19135437

78. Smith RP, Taher L, Patwardhan RP, Kim MJ, Inoue F, et al. (2013) Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model. Nat Genet 45: 1021–1028. doi: 10.1038/ng.2713 23892608

79. Papatsenko D, Goltsev Y, Levine M (2009) Organization of developmental enhancers in the Drosophila embryo. Nucleic Acids Res 37: 5665–5677. doi: 10.1093/nar/gkp619 19651877

80. Arnosti DN, Kulkarni MM (2005) Transcriptional enhancers: Intelligent enhanceosomes or flexible billboards? J Cell Biochem 94: 890–898. 15696541

81. Papatsenko D, Levine M (2007) A rationale for the enhanceosome and other evolutionarily constrained enhancers. Curr Biol 17: R955–R957. 18029246

82. Swanson CI, Schwimmer DB, Barolo S (2011) Rapid Evolutionary Rewiring of a Structurally Constrained Eye Enhancer. Curr Biol 21: 1186–1196. doi: 10.1016/j.cub.2011.05.056 21737276

83. Crocker J, Tamori Y, Erives A (2008) Evolution acts on enhancer organization to fine-tune gradient threshold readouts. PLoS Biol 6: e263. doi: 10.1371/journal.pbio.0060263 18986212

84. Couthier A, Smith J, McGarr P, Craig B, Gilleard JS (2004) Ectopic expression of a Haemonchus contortus GATA transcription factor in Caenorhabditis elegans reveals conserved function in spite of extensive sequence divergence. Mol Biochem Parasitol 133: 241–253. 14698436

85. Xu S, Fire A, Seydoux G, Okkema P (1995) Fire Lab Vector Kit. June 1995.

86. Granato M, Schnabel H, Schnabel R (1994) pha-1, a selectable marker for gene-transfer in C. elegans. Nucleic Acids Res 22: 1762–1763. 8202383

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