Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell

English version

Autoři: Bogdan Sieriebriennikov ^aff001; Shuai Sun ^aff001; James W. Lightfoot ^aff001; Hanh Witte ^aff001; Eduardo Moreno ^aff001; Christian Rödelsperger ^aff001; Ralf J. Sommer ^aff001
Působiště autorů: Department for Integrative Evolutionary Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany ^aff001
Vyšlo v časopise: Conserved nuclear hormone receptors controlling a novel plastic trait target fast-evolving genes expressed in a single cell. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008687
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008687

Souhrn

Environment shapes development through a phenomenon called developmental plasticity. Deciphering its genetic basis has potential to shed light on the origin of novel traits and adaptation to environmental change. However, molecular studies are scarce, and little is known about molecular mechanisms associated with plasticity. We investigated the gene regulatory network controlling predatory vs. non-predatory dimorphism in the nematode Pristionchus pacificus and found that it consists of genes of extremely different age classes. We isolated mutants in the conserved nuclear hormone receptor nhr-1 with previously unseen phenotypic effects. They disrupt mouth-form determination and result in animals combining features of both wild-type morphs. In contrast, mutants in another conserved nuclear hormone receptor nhr-40 display altered morph ratios, but no intermediate morphology. Despite divergent modes of control, NHR-1 and NHR-40 share transcriptional targets, which encode extracellular proteins that have no orthologs in Caenorhabditis elegans and result from lineage-specific expansions. An array of transcriptional reporters revealed co-expression of all tested targets in the same pharyngeal gland cell. Major morphological changes in this gland cell accompanied the evolution of teeth and predation, linking rapid gene turnover with morphological innovations. Thus, the origin of feeding plasticity involved novelty at the level of genes, cells and behavior.

Klíčová slova:

Alleles – Caenorhabditis elegans – Evolutionary genetics – Gene regulation – Invertebrate genomics – Phenotypes – Protein domains – Teeth

Zdroje

1. West-Eberhard MJ. Developmental plasticity and evolution. Oxford; New York: Oxford University Press; 2003.

2. Corona M, Libbrecht R, Wheeler DE. Molecular mechanisms of phenotypic plasticity in social insects. Curr Opin Insect Sci. 2016;13: 55–60. doi: 10.1016/j.cois.2015.12.003 27436553

3. Nicotra AB, Atkin OK, Bonser SP, Davidson AM, Finnegan EJ, Mathesius U, et al. Plant phenotypic plasticity in a changing climate. Trends Plant Sci. 2010;15: 684–692. doi: 10.1016/j.tplants.2010.09.008 20970368

4. Seebacher F, White CR, Franklin CE. Physiological plasticity increases resilience of ectothermic animals to climate change. Nat Clim Chang. 2014;5: 61.

5. Charmantier A, McCleery RH, Cole LR, Perrins C, Kruuk LEB, Sheldon BC. Adaptive phenotypic plasticity in response to climate change in a wild bird population. Science. 2008;320: 800–803. doi: 10.1126/science.1157174 18467590

6. Oostra V, Saastamoinen M, Zwaan BJ, Wheat CW. Strong phenotypic plasticity limits potential for evolutionary responses to climate change. Nat Commun. 2018;9: 1005. doi: 10.1038/s41467-018-03384-9 29520061

7. Susoy V, Ragsdale EJ, Kanzaki N, Sommer RJ. Rapid diversification associated with a macroevolutionary pulse of developmental plasticity. Elife. 2015;4: e05463.

8. West-Eberhard MJ. Developmental plasticity and the origin of species differences. Proc Natl Acad Sci U S A. 2005;102 Suppl 1: 6543–6549.

9. Corl A, Bi K, Luke C, Challa AS, Stern AJ, Sinervo B, et al. The Genetic Basis of Adaptation following Plastic Changes in Coloration in a Novel Environment. Curr Biol. 2018;28: 2970–2977.e7. doi: 10.1016/j.cub.2018.06.075 30197088

10. Wund MA, Baker JA, Clancy B, Golub JL, Foster SA. A test of the “flexible stem” model of evolution: ancestral plasticity, genetic accommodation, and morphological divergence in the threespine stickleback radiation. Am Nat. 2008;172: 449–462. doi: 10.1086/590966 18729721

11. Levis NA, Pfennig DW. Phenotypic plasticity, canalization, and the origins of novelty: Evidence and mechanisms from amphibians. Semin Cell Dev Biol. 2019;88: 80–90. doi: 10.1016/j.semcdb.2018.01.012 29408711

12. Ghalambor CK, Hoke KL, Ruell EW, Fischer EK, Reznick DN, Hughes KA. Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature. Nature. 2015;525: 372–375. doi: 10.1038/nature15256 26331546

13. Sommer RJ, Dardiry M, Lenuzzi M, Namdeo S, Renahan T, Sieriebriennikov B, et al. The genetics of phenotypic plasticity in nematode feeding structures. Open Biol. 2017;7: 160332. doi: 10.1098/rsob.160332 28298309

14. Projecto-Garcia J, Biddle JF, Ragsdale EJ. Decoding the architecture and origins of mechanisms for developmental polyphenism. Curr Opin Genet Dev. 2017;47: 1–8. doi: 10.1016/j.gde.2017.07.015 28810163

15. Opachaloemphan C, Yan H, Leibholz A, Desplan C, Reinberg D. Recent Advances in Behavioral (Epi)Genetics in Eusocial Insects. Annu Rev Genet. 2018;52: 489–510. doi: 10.1146/annurev-genet-120116-024456 30208294

16. Moczek AP, Sultan S, Foster S, Ledón-Rettig C, Dworkin I, Nijhout HF, et al. The role of developmental plasticity in evolutionary innovation. Proc Biol Sci. 2011;278: 2705–2713. doi: 10.1098/rspb.2011.0971 21676977

17. Bento G, Ogawa A, Sommer RJ. Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution. Nature. 2010;466: 494–499. doi: 10.1038/nature09164 20592728

18. Ragsdale EJ, Müller MR, Rödelsperger C, Sommer RJ. A Developmental Switch Coupled to the Evolution of Plasticity Acts through a Sulfatase. Cell. 2013;155: 922–933. doi: 10.1016/j.cell.2013.09.054 24209628

19. Werner MS, Sieriebriennikov B, Loschko T, Namdeo S, Lenuzzi M, Dardiry M, et al. Environmental influence on Pristionchus pacificus mouth form through different culture methods. Sci Rep. 2017;7: 7207. doi: 10.1038/s41598-017-07455-7 28775277

20. Bose N, Ogawa A, von Reuss SH, Yim JJ, Ragsdale EJ, Sommer RJ, et al. Complex small-molecule architectures regulate phenotypic plasticity in a nematode. Angew Chem Int Ed Engl. 2012;51: 12438–12443. doi: 10.1002/anie.201206797 23161728

21. Werner MS, Claaßen MH, Renahan T, Dardiry M, Sommer RJ. Adult Influence on Juvenile Phenotypes by Stage-Specific Pheromone Production. iScience. 2018;10: 123–134. doi: 10.1016/j.isci.2018.11.027 30513394

22. Sieriebriennikov B, Prabh N, Dardiry M, Witte H, Röseler W, Kieninger MR, et al. A Developmental Switch Generating Phenotypic Plasticity Is Part of a Conserved Multi-gene Locus. Cell Rep. 2018;23: 2835–2843.e4. doi: 10.1016/j.celrep.2018.05.008 29874571

23. Namdeo S, Moreno E, Rödelsperger C, Baskaran P, Witte H, Sommer RJ. Two independent sulfation processes regulate mouth-form plasticity in the nematode Pristionchus pacificus. Development. 2018;145: dev166272. doi: 10.1242/dev.166272 29967123

24. Bui LT, Ivers NA, Ragsdale EJ. A sulfotransferase dosage-dependently regulates mouthpart polyphenism in the nematode Pristionchus pacificus. Nat Commun. 2018;9: 4119. doi: 10.1038/s41467-018-05612-8 30297689

25. Bui LT, Ragsdale EJ. Multiple plasticity regulators reveal targets specifying an induced predatory form in nematodes. Molecular Biology and Evolution. 2019. doi: 10.1093/molbev/msz171 31364718

26. Serobyan V, Xiao H, Namdeo S, Rödelsperger C, Sieriebriennikov B, Witte H, et al. Chromatin remodelling and antisense-mediated up-regulation of the developmental switch gene eud-1 control predatory feeding plasticity. Nat Commun. 2016;7: 12337. doi: 10.1038/ncomms12337 27487725

27. Kieninger MR, Ivers NA, Rödelsperger C, Markov GV, Sommer RJ, Ragsdale EJ. The Nuclear Hormone Receptor NHR-40 Acts Downstream of the Sulfatase EUD-1 as Part of a Developmental Plasticity Switch in Pristionchus. Curr Biol. 2016;26: 2174–2179. doi: 10.1016/j.cub.2016.06.018 27451902

28. Sluder AE, Mathews SW, Hough D, Yin VP, Maina CV. The nuclear receptor superfamily has undergone extensive proliferation and diversification in nematodes. Genome Res. 1999;9: 103–120. 10022975

29. Evans RM, Mangelsdorf DJ. Nuclear Receptors, RXR, and the Big Bang. Cell. 2014;157: 255–266. doi: 10.1016/j.cell.2014.03.012 24679540

30. Brozová E, Simecková K, Kostrouch Z, Rall JE, Kostrouchová M. NHR-40, a Caenorhabditis elegans supplementary nuclear receptor, regulates embryonic and early larval development. Mech Dev. 2006;123: 689–701. doi: 10.1016/j.mod.2006.06.006 16920335

31. Crews ST, Pearson JC. Transcriptional autoregulation in development. Curr Biol. 2009;19: R241–6. doi: 10.1016/j.cub.2009.01.015 19321138

32. Mangan S, Alon U. Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci U S A. 2003;100: 11980–11985. doi: 10.1073/pnas.2133841100 14530388

33. Macneil LT, Walhout AJM. Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression. Genome Res. 2011;21: 645–657. doi: 10.1101/gr.097378.109 21324878

34. Bulcha JT, Giese GE, Ali MZ, Lee Y-U, Walker MD, Holdorf AD, et al. A Persistence Detector for Metabolic Network Rewiring in an Animal. Cell Rep. 2019;26: 460–468.e4. doi: 10.1016/j.celrep.2018.12.064 30625328

35. Abdusselamoglu MD, Eroglu E, Burkard TR, Knoblich JA. The transcription factor odd-paired regulates temporal identity in transit-amplifying neural progenitors via an incoherent feed-forward loop. Elife. 2019;8: e46566. doi: 10.7554/eLife.46566 31329099

36. Taylor-Teeples M, Lin L, de Lucas M, Turco G, Toal TW, Gaudinier A, et al. An Arabidopsis gene regulatory network for secondary cell wall synthesis. Nature. 2015;517: 571–575. doi: 10.1038/nature14099 25533953

37. Jaumouillé E, Machado Almeida P, Stähli P, Koch R, Nagoshi E. Transcriptional regulation via nuclear receptor crosstalk required for the Drosophila circadian clock. Curr Biol. 2015;25: 1502–1508. doi: 10.1016/j.cub.2015.04.017 26004759

38. Anbalagan M, Huderson B, Murphy L, Rowan BG. Post-translational modifications of nuclear receptors and human disease. Nucl Recept Signal. 2012;10: e001. doi: 10.1621/nrs.10001 22438791

39. Serobyan V, Ragsdale EJ, Müller MR, Sommer RJ. Feeding plasticity in the nematode Pristionchus pacificus is influenced by sex and social context and is linked to developmental speed. Evol Dev. 2013;15: 161–170. doi: 10.1111/ede.12030 23607300

40. Hirschmann H. Über das Vorkommen zweier Mundhöhlentypen bei Diplogaster lheritieri Maupas und Diplogaster biformis n. sp. und die Entstehung dieser hermaphroditischen Art aus Diplogaster lheritieri. Zool Jb, Abt System, Ökol u Geogr. 1951;80: 132–170.

41. Reinke V, Gil IS, Ward S, Kazmer K. Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development. 2004;131: 311–323. doi: 10.1242/dev.00914 14668411

42. Gomis-Rüth FX, Trillo-Muyo S, Stöcker W. Functional and structural insights into astacin metallopeptidases. Biol Chem. 2012;393: 1027–1041. doi: 10.1515/hsz-2012-0149 23092796

43. Novelli J, Ahmed S, Hodgkin J. Gene interactions in Caenorhabditis elegans define DPY-31 as a candidate procollagen C-proteinase and SQT-3/ROL-4 as its predicted major target. Genetics. 2004;168: 1259–1273. doi: 10.1534/genetics.104.027953 15579684

44. Park J-O, Pan J, Möhrlen F, Schupp M-O, Johnsen R, Baillie DL, et al. Characterization of the astacin family of metalloproteases in C. elegans. BMC Dev Biol. 2010;10: 14. doi: 10.1186/1471-213X-10-14 20109220

45. Li Y, Zhao Y, Su M, Glover K, Chakravarthy S, Colbert CL, et al. Structural insights into the interaction of the conserved mammalian proteins GAPR-1 and Beclin 1, a key autophagy protein. Acta Crystallogr D Struct Biol. 2017;73: 775–792. doi: 10.1107/S2059798317011822 28876241

46. Darwiche R, Kelleher A, Hudspeth EM, Schneiter R, Asojo OA. Structural and functional characterization of the CAP domain of pathogen-related yeast 1 (Pry1) protein. Sci Rep. 2016;6: 28838. doi: 10.1038/srep28838 27344972

47. Choudhary V, Schneiter R. Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins. Proc Natl Acad Sci U S A. 2012;109: 16882–16887. doi: 10.1073/pnas.1209086109 23027975

48. Gibbs GM, Roelants K, O’Bryan MK. The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins—roles in reproduction, cancer, and immune defense. Endocr Rev. 2008;29: 865–897. doi: 10.1210/er.2008-0032 18824526

49. Henrissat B, Callebaut I, Fabrega S, Lehn P, Mornon JP, Davies G. Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases. Proc Natl Acad Sci U S A. 1995;92: 7090–7094. doi: 10.1073/pnas.92.15.7090 7624375

50. Lints R, Hall DH. The cuticle. WormAtlas. 2009.

51. Tokareva O, Jacobsen M, Buehler M, Wong J, Kaplan DL. Structure-function-property-design interplay in biopolymers: spider silk. Acta Biomater. 2014;10: 1612–1626. doi: 10.1016/j.actbio.2013.08.020 23962644

52. Guan J, Vollrath F, Porter D. Two mechanisms for supercontraction in Nephila spider dragline silk. Biomacromolecules. 2011;12: 4030–4035. doi: 10.1021/bm201032v 21951163

53. Riebesell M, Sommer RJ. Three-dimensional reconstruction of the pharyngeal gland cells in the predatory nematode Pristionchus pacificus. Journal of Morphology. 2017;278: 1656–1666. doi: 10.1002/jmor.20739 28898441

54. van Megen H, van den Elsen S, Holterman M, Karssen G, Mooyman P, Bongers T, et al. A phylogenetic tree of nematodes based on about 1200 full-length small subunit ribosomal DNA sequences. Nematology. 2009;11: 927–950.

55. Altun ZF, Hall DH. Alimentary System, Pharynx. WormAtlas. 2009.

56. Zhang YC, Baldwin JG. Ultrastructure of the postcorpus of the esophagus of Teratocephalus lirellus (Teratocephalida) and its use for interpreting character evolution in Secernentea (Nematoda). Can J Zool. 2001;79: 16–25.

57. Zhang YC, Baldwin JG. Ultrastructure of the post–corpus of Zeldia punctata (Cephalobina) for analysis of the evolutionary framework of nematodes related to Caenorhabditis elegans (Rhabditina). Proceedings of the Royal Society of London Series B: Biological Sciences. 2000;267: 1229–1238. doi: 10.1098/rspb.2000.1132 10902689

58. Chiang J- TA, Steciuk M, Shtonda B, Avery L. Evolution of pharyngeal behaviors and neuronal functions in free-living soil nematodes. J Exp Biol. 2006;209: 1859–1873. doi: 10.1242/jeb.02165 16651552

59. Zhang YC, Baldwin JG. Ultrastructure of the Esophagus of Diplenteron sp. (Diplogasterida) to Test Hypotheses of Homology with Rhabditida and Tylenchida. J Nematol. 1999;31: 1–19. 19270870

60. Prabh N, Roeseler W, Witte H, Eberhardt G, Sommer RJ, Rödelsperger C. Deep taxon sampling reveals the evolutionary dynamics of novel gene families in Pristionchus nematodes. Genome Res. 2018;28: 1664–1674. doi: 10.1101/gr.234971.118 30232197

61. Dieterich C, Clifton SW, Schuster LN, Chinwalla A, Delehaunty K, Dinkelacker I, et al. The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism. Nat Genet. 2008;40: 1193–1198. doi: 10.1038/ng.227 18806794

62. Markov GV, Baskaran P, Sommer RJ. The same or not the same: lineage-specific gene expansions and homology relationships in multigene families in nematodes. J Mol Evol. 2015;80: 18–36. doi: 10.1007/s00239-014-9651-y 25323991

63. Sieriebriennikov B, Markov GV, Witte H, Sommer RJ. The Role of DAF-21/Hsp90 in Mouth-Form Plasticity in Pristionchus pacificus. Mol Biol Evol. 2017;34: 1644–1653. doi: 10.1093/molbev/msx106 28333289

64. Antebi A, Yeh WH, Tait D, Hedgecock EM, Riddle DL. daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes Dev. 2000;14: 1512–1527. 10859169

65. Burton NO, Dwivedi VK, Burkhart KB, Kaplan REW, Baugh LR, Horvitz HR. Neurohormonal signaling via a sulfotransferase antagonizes insulin-like signaling to regulate a Caenorhabditis elegans stress response. Nat Commun. 2018;9: 5152. doi: 10.1038/s41467-018-07640-w 30514845

66. Rödelsperger C, Streit A, Sommer RJ. Structure, Function and Evolution of The Nematode Genome. eLS. Chichester, UK: John Wiley & Sons, Ltd; 2013.

67. Mitreva M, Blaxter ML, Bird DM, McCarter JP. Comparative genomics of nematodes. Trends Genet. 2005;21: 573–581. doi: 10.1016/j.tig.2005.08.003 16099532

68. Manning G, Plowman GD, Hunter T, Sudarsanam S. Evolution of protein kinase signaling from yeast to man. Trends Biochem Sci. 2002;27: 514–520. doi: 10.1016/s0968-0004(02)02179-5 12368087

69. Goodrich LV, Johnson RL, Milenkovic L, McMahon JA, Scott MP. Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog. Genes Dev. 1996;10: 301–312. doi: 10.1101/gad.10.3.301 8595881

70. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20: 781–810. doi: 10.1146/annurev.cellbio.20.010403.113126 15473860

71. Stiernagle T. Maintenance of C. elegans (February 11, 2006). In: The C. elegans research community, editor. WormBook. 2016.

72. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9: 676–682. doi: 10.1038/nmeth.2019 22743772

73. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing; 2016.

74. Adams DC, Otarola-Castillo E. geomorph: an R package for the collection and analysis of geometric morphometric shape data. Methods Ecol Evol. 2013;4: 393–399.

75. Witte H, Moreno E, Rödelsperger C, Kim J, Kim JS, Streit A, et al. Gene inactivation using the CRISPR/Cas9 system in the nematode Pristionchus pacificus. Dev Genes Evol. 2015;225: 55–62. doi: 10.1007/s00427-014-0486-8 25548084

76. Lightfoot JW, Wilecki M, Rödelsperger C, Moreno E, Susoy V, Witte H, et al. Small peptide-mediated self-recognition prevents cannibalism in predatory nematodes. Science. 2019;364: 86–89. doi: 10.1126/science.aav9856 30948551

77. Zhou S, Fu X, Pei P, Kucka M, Liu J, Tang L, et al. Characterization of a non-sexual population of Strongyloides stercoralis with hybrid 18S rDNA haplotypes in Guangxi, Southern China. PLoS Negl Trop Dis. 2019;13: e0007396. doi: 10.1371/journal.pntd.0007396 31059500

78. Rödelsperger C, Meyer JM, Prabh N, Lanz C, Bemm F, Sommer RJ. Single-Molecule Sequencing Reveals the Chromosome-Scale Genomic Architecture of the Nematode Model Organism Pristionchus pacificus. Cell Rep. 2017;21: 834–844. doi: 10.1016/j.celrep.2017.09.077 29045848

79. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9: 357–359. doi: 10.1038/nmeth.1923 22388286

80. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nat Biotechnol. 2011;29: 24–26. doi: 10.1038/nbt.1754 21221095

81. Pires-daSilva A. Pristionchus pacificus protocols (March 14, 2013). In: The C. elegans research community, editor. WormBook. 2013.

82. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25: 1754–1760. doi: 10.1093/bioinformatics/btp324 19451168

83. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25: 2078–2079. doi: 10.1093/bioinformatics/btp352 19505943

84. Rae R, Witte H, Rödelsperger C, Sommer RJ. The importance of being regular: Caenorhabditis elegans and Pristionchus pacificus defecation mutants are hypersusceptible to bacterial pathogens. Int J Parasitol. 2012;42: 747–753. doi: 10.1016/j.ijpara.2012.05.005 22705203

85. Schlager B, Wang X, Braach G, Sommer RJ. Molecular cloning of a dominant roller mutant and establishment of DNA-mediated transformation in the nematode Pristionchus pacificus. Genesis. 2009;47: 300–304. doi: 10.1002/dvg.20499 19298013

86. OpenWetWare contributors. Gibson Assembly. In: OpenWetWare [Internet]. 7 May 2018 [cited 25 Jul 2018]. Available: https://openwetware.org/mediawiki/index.php?title = Gibson_Assembly&oldid = 1043969

87. Bettinger JC, Lee K, Rougvie AE. Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development. 1996;122: 2517–2527. 8756296

88. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29: 15–21. doi: 10.1093/bioinformatics/bts635 23104886

89. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5: R80. doi: 10.1186/gb-2004-5-10-r80 15461798

90. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15: 550. doi: 10.1186/s13059-014-0550-8 25516281

91. Fox J, Weisberg S. An R Companion to Applied Regression. Thousand Oaks CA: Sage; 2019. Available: https://socialsciences.mcmaster.ca/jfox/Books/Companion/

92. Nielsen H. Predicting Secretory Proteins with SignalP. Methods Mol Biol. 2017;1611: 59–73. doi: 10.1007/978-1-4939-7015-5_6 28451972

93. Möhrlen F, Hutter H, Zwilling R. The astacin protein family in Caenorhabditis elegans. Eur J Biochem. 2003;270: 4909–4920. doi: 10.1046/j.1432-1033.2003.03891.x 14653817

94. Finn RD, Coggill P, Eberhardt RY, Eddy SR, Mistry J, Mitchell AL, et al. The Pfam protein families database: towards a more sustainable future. Nucleic Acids Res. 2016;44: D279–85. doi: 10.1093/nar/gkv1344 26673716

95. Sinha A, Langnick C, Sommer RJ, Dieterich C. Genome-wide analysis of trans-splicing in the nematode Pristionchus pacificus unravels conserved gene functions for germline and dauer development in divergent operons. RNA. 2014;20: 1386–1397. doi: 10.1261/rna.041954.113 25015138

96. Werner MS, Sieriebriennikov B, Prabh N, Loschko T, Lanz C, Sommer RJ. Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation. Genome Res. 2018;28: 1675–1687. doi: 10.1101/gr.234872.118 30232198

97. Rödelsperger C, Athanasouli M, Lenuzzi M, Theska T, Sun S, Dardiry M, Wighard S, Hu W, Sharma DR, Han Z. Crowdsourcing and the feasibility of manual gene annotation: A pilot study in the nematode Pristionchus pacificus. Sci. Rep. 2019;9: 18789. doi: 10.1038/s41598-019-55359-5 31827189

98. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30: 772–780. doi: 10.1093/molbev/mst010 23329690

99. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30: 1312–1313. doi: 10.1093/bioinformatics/btu033 24451623

Článek High expression in maize pollen correlates with genetic contributions to pollen fitness as well as with coordinated transcription from neighboring transposable elements

Článek XPF-ERCC1 protects liver, kidney and blood homeostasis outside the canonical excision repair pathways

Článek The nanophthalmos protein TMEM98 inhibits MYRF self-cleavage and is required for eye size specification

Článek Is imprinting the result of “friendly fire” by the host defense system?

Článek XPF–ERCC1: Linchpin of DNA crosslink repair

Článek A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease

Článek Deconstructing cerebellar development cell by cell

Článek Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans

Článek Molecular genetics of maternally-controlled cell divisions

Článek An integrated analysis of cell-type specific gene expression reveals genes regulated by REVOLUTA and KANADI1 in the Arabidopsis shoot apical meristem

Článek Loss-of-function tolerance of enhancers in the human genome

Článek Is adaptation limited by mutation? A timescale-dependent effect of genetic diversity on the adaptive substitution rate in animals