A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans


Autoři: Yuehui Zhao aff001;  Lijiang Long aff001;  Jason Wan aff003;  Shweta Biliya aff001;  Shannon C. Brady aff004;  Daehan Lee aff004;  Akinade Ojemakinde aff001;  Erik C. Andersen aff004;  Fredrik O. Vannberg aff001;  Hang Lu aff005;  Patrick T. McGrath aff001
Působiště autorů: School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff001;  Interdisciplinary Graduate Program in Quantitative Biosciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff002;  The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America aff003;  Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America aff004;  Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff005;  School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff006;  School of Physics, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff007
Vyšlo v časopise: A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans. PLoS Genet 16(2): e32767. doi:10.1371/journal.pgen.1008606
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008606

Souhrn

Over long evolutionary timescales, major changes to the copy number, function, and genomic organization of genes occur, however, our understanding of the individual mutational events responsible for these changes is lacking. In this report, we study the genetic basis of adaptation of two strains of C. elegans to laboratory food sources using competition experiments on a panel of 89 recombinant inbred lines (RIL). Unexpectedly, we identified a single RIL with higher relative fitness than either of the parental strains. This strain also displayed a novel behavioral phenotype, resulting in higher propensity to explore bacterial lawns. Using bulk-segregant analysis and short-read resequencing of this RIL, we mapped the change in exploration behavior to a spontaneous, complex rearrangement of the rcan-1 gene that occurred during construction of the RIL panel. We resolved this rearrangement into five unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1 calcipressin gene, which has been implicated as a causal gene for Down syndrome. The genomic rearrangement in rcan-1 creates two complete and two truncated versions of the rcan-1 coding region, with a variety of modified 5’ and 3’ non-coding regions. While most copy-number variations (CNVs) are thought to act by increasing expression of duplicated genes, these changes to rcan-1 ultimately result in the reduction of its whole-body expression due to changes in the upstream regions. By backcrossing this rearrangement into a common genetic background to create a near isogenic line (NIL), we demonstrate that both the competitive advantage and exploration behavioral changes are linked to this complex genetic variant. This NIL strain does not phenocopy a strain containing an rcan-1 loss-of-function allele, which suggests that the residual expression of rcan-1 is necessary for its fitness effects. Our results demonstrate how colonization of new environments, such as those encountered in the laboratory, can create evolutionary pressure to modify gene function. This evolutionary mismatch can be resolved by an unexpectedly complex genetic change that simultaneously duplicates and diversifies a gene into two uniquely regulated genes. Our work shows how complex rearrangements can act to modify gene expression in ways besides increased gene dosage.

Klíčová slova:

Behavior – Caenorhabditis elegans – Evolutionary genetics – Gene expression – Genome complexity – Inbred strains – Polymerase chain reaction – Sequence alignment


Zdroje

1. Maydan JS, Lorch A, Edgley ML, Flibotte S, Moerman DG. Copy number variation in the genomes of twelve natural isolates of Caenorhabditis elegans. BMC Genomics. 2010;11:62. Epub 2010/01/27. doi: 10.1186/1471-2164-11-62 20100350; PubMed Central PMCID: PMC2822765.

2. Katju V, Bergthorsson U. Copy-number changes in evolution: rates, fitness effects and adaptive significance. Front Genet. 2013;4:273. Epub 2013/12/26. doi: 10.3389/fgene.2013.00273 24368910; PubMed Central PMCID: PMC3857721.

3. Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, et al. An integrated map of structural variation in 2,504 human genomes. Nature. 2015;526(7571):75–81. Epub 2015/10/04. doi: 10.1038/nature15394 26432246; PubMed Central PMCID: PMC4617611.

4. Long E, Evans C, Chaston J, Udall JA. Genomic Structural Variations Within Five Continental Populations of Drosophila melanogaster. G3 (Bethesda). 2018;8(10):3247–53. Epub 2018/08/17. doi: 10.1534/g3.118.200631 30111620; PubMed Central PMCID: PMC6169376.

5. Audano PA, Sulovari A, Graves-Lindsay TA, Cantsilieris S, Sorensen M, Welch AE, et al. Characterizing the Major Structural Variant Alleles of the Human Genome. Cell. 2019;176(3):663–75 e19. Epub 2019/01/22. doi: 10.1016/j.cell.2018.12.019 30661756; PubMed Central PMCID: PMC6438697.

6. Fuentes RR, Chebotarov D, Duitama J, Smith S, De la Hoz JF, Mohiyuddin M, et al. Structural variants in 3000 rice genomes. Genome Res. 2019;29(5):870–80. Epub 2019/04/18. doi: 10.1101/gr.241240.118 30992303; PubMed Central PMCID: PMC6499320.

7. Lupski JR. Genomic rearrangements and sporadic disease. Nat Genet. 2007;39(7 Suppl):S43–7. Epub 2007/09/05. doi: 10.1038/ng2084 17597781.

8. Chen JM, Cooper DN, Ferec C, Kehrer-Sawatzki H, Patrinos GP. Genomic rearrangements in inherited disease and cancer. Semin Cancer Biol. 2010;20(4):222–33. Epub 2010/06/15. doi: 10.1016/j.semcancer.2010.05.007 20541013.

9. Martin CL, Kirkpatrick BE, Ledbetter DH. Copy number variants, aneuploidies, and human disease. Clin Perinatol. 2015;42(2):227–42, vii. Epub 2015/06/05. doi: 10.1016/j.clp.2015.03.001 26042902; PubMed Central PMCID: PMC4459515.

10. Rice AM, McLysaght A. Dosage sensitivity is a major determinant of human copy number variant pathogenicity. Nat Commun. 2017;8:14366. Epub 2017/02/09. doi: 10.1038/ncomms14366 28176757; PubMed Central PMCID: PMC5309798.

11. Hieronymus H, Murali R, Tin A, Yadav K, Abida W, Moller H, et al. Tumor copy number alteration burden is a pan-cancer prognostic factor associated with recurrence and death. Elife. 2018;7. Epub 2018/09/05. doi: 10.7554/eLife.37294 PubMed Central PMCID: PMC6145837. 30178746

12. Chain FJ, Feulner PG. Ecological and evolutionary implications of genomic structural variations. Front Genet. 2014;5:326. Epub 2014/10/04. doi: 10.3389/fgene.2014.00326 25278961; PubMed Central PMCID: PMC4165313.

13. Fan S, Meyer A. Evolution of genomic structural variation and genomic architecture in the adaptive radiations of African cichlid fishes. Front Genet. 2014;5:163. Epub 2014/06/12. doi: 10.3389/fgene.2014.00163 24917883; PubMed Central PMCID: PMC4042683.

14. Wellenreuther M, Merot C, Berdan E, Bernatchez L. Going beyond SNPs: The role of structural genomic variants in adaptive evolution and species diversification. Mol Ecol. 2019;28(6):1203–9. Epub 2019/03/06. doi: 10.1111/mec.15066 30834648.

15. Lye ZN, Purugganan MD. Copy Number Variation in Domestication. Trends Plant Sci. 2019;24(4):352–65. Epub 2019/02/13. doi: 10.1016/j.tplants.2019.01.003 30745056.

16. Dorshorst B, Molin AM, Rubin CJ, Johansson AM, Stromstedt L, Pham MH, et al. A complex genomic rearrangement involving the endothelin 3 locus causes dermal hyperpigmentation in the chicken. PLoS Genet. 2011;7(12):e1002412. Epub 2012/01/05. doi: 10.1371/journal.pgen.1002412 22216010; PubMed Central PMCID: PMC3245302.

17. Cook DE, Lee TG, Guo X, Melito S, Wang K, Bayless AM, et al. Copy number variation of multiple genes at Rhg1 mediates nematode resistance in soybean. Science. 2012;338(6111):1206–9. Epub 2012/10/16. doi: 10.1126/science.1228746 23065905.

18. Durkin K, Coppieters W, Drogemuller C, Ahariz N, Cambisano N, Druet T, et al. Serial translocation by means of circular intermediates underlies colour sidedness in cattle. Nature. 2012;482(7383):81–4. Epub 2012/02/03. doi: 10.1038/nature10757 22297974.

19. Wang Y, Xiong G, Hu J, Jiang L, Yu H, Xu J, et al. Copy number variation at the GL7 locus contributes to grain size diversity in rice. Nat Genet. 2015;47(8):944–8. Epub 2015/07/07. doi: 10.1038/ng.3346 26147619.

20. Yassin A, Delaney EK, Reddiex AJ, Seher TD, Bastide H, Appleton NC, et al. The pdm3 Locus Is a Hotspot for Recurrent Evolution of Female-Limited Color Dimorphism in Drosophila. Curr Biol. 2016;26(18):2412–22. Epub 2016/08/23. doi: 10.1016/j.cub.2016.07.016 27546577; PubMed Central PMCID: PMC5450831.

21. Ohno S. Evolution by gene duplication. Berlin, New York,: Springer-Verlag; 1970. xv, 160 p. p.

22. Taylor JS, Raes J. Duplication and divergence: the evolution of new genes and old ideas. Annu Rev Genet. 2004;38:615–43. Epub 2004/12/01. doi: 10.1146/annurev.genet.38.072902.092831 15568988.

23. Kunte K, Zhang W, Tenger-Trolander A, Palmer DH, Martin A, Reed RD, et al. doublesex is a mimicry supergene. Nature. 2014;507(7491):229–32. Epub 2014/03/07. doi: 10.1038/nature13112 24598547.

24. Tuttle EM, Bergland AO, Korody ML, Brewer MS, Newhouse DJ, Minx P, et al. Divergence and Functional Degradation of a Sex Chromosome-like Supergene. Curr Biol. 2016;26(3):344–50. Epub 2016/01/26. doi: 10.1016/j.cub.2015.11.069 26804558; PubMed Central PMCID: PMC4747794.

25. Fuller ZL, Koury SA, Phadnis N, Schaeffer SW. How chromosomal rearrangements shape adaptation and speciation: Case studies in Drosophila pseudoobscura and its sibling species Drosophila persimilis. Mol Ecol. 2019;28(6):1283–301. Epub 2018/11/08. doi: 10.1111/mec.14923 30402909; PubMed Central PMCID: PMC6475473.

26. Barrick JE, Yu DS, Yoon SH, Jeong H, Oh TK, Schneider D, et al. Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature. 2009;461(7268):1243. doi: 10.1038/nature08480 19838166

27. Blount ZD, Borland CZ, Lenski RE. Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli. Proc Natl Acad Sci U S A. 2008;105(23):7899–906. Epub 2008/06/06. doi: 10.1073/pnas.0803151105 18524956; PubMed Central PMCID: PMC2430337.

28. Brown CJ, Todd KM, Rosenzweig RF. Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment. Mol Biol Evol. 1998;15(8):931–42. Epub 1998/08/27. doi: 10.1093/oxfordjournals.molbev.a026009 9718721.

29. Dunham MJ, Badrane H, Ferea T, Adams J, Brown PO, Rosenzweig F, et al. Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2002;99(25):16144–9. Epub 2002/11/26. doi: 10.1073/pnas.242624799 12446845; PubMed Central PMCID: PMC138579.

30. Elena SF, Lenski RE. Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Nat Rev Genet. 2003;4(6):457–69. Epub 2003/05/31. doi: 10.1038/nrg1088 12776215.

31. Gresham D, Desai MM, Tucker CM, Jenq HT, Pai DA, Ward A, et al. The repertoire and dynamics of evolutionary adaptations to controlled nutrient-limited environments in yeast. PLoS Genet. 2008;4(12):e1000303. Epub 2008/12/17. doi: 10.1371/journal.pgen.1000303 19079573; PubMed Central PMCID: PMC2586090.

32. Kao KC, Sherlock G. Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae. Nat Genet. 2008;40(12):1499–504. Epub 2008/11/26. doi: 10.1038/ng.280 19029899; PubMed Central PMCID: PMC2596280.

33. Kasahara T, Abe K, Mekada K, Yoshiki A, Kato T. Genetic variation of melatonin productivity in laboratory mice under domestication. Proc Natl Acad Sci U S A. 2010;107(14):6412–7. Epub 2010/03/24. doi: 10.1073/pnas.0914399107 20308563; PubMed Central PMCID: PMC2851971.

34. Levy SF, Blundell JR, Venkataram S, Petrov DA, Fisher DS, Sherlock G. Quantitative evolutionary dynamics using high-resolution lineage tracking. Nature. 2015;519(7542):181. doi: 10.1038/nature14279 25731169

35. Orozco-terWengel P, Kapun M, Nolte V, Kofler R, Flatt T, Schlotterer C. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles. Mol Ecol. 2012;21(20):4931–41. Epub 2012/06/26. doi: 10.1111/j.1365-294X.2012.05673.x 22726122; PubMed Central PMCID: PMC3533796.

36. Ratcliff WC, Denison RF, Borrello M, Travisano M. Experimental evolution of multicellularity. Proc Natl Acad Sci U S A. 2012;109(5):1595–600. Epub 2012/02/07. doi: 10.1073/pnas.1115323109 22307617; PubMed Central PMCID: PMC3277146.

37. Rose MR. Artificial Selection on a Fitness-Component in Drosophila Melanogaster. Evolution. 1984;38(3):516–26. Epub 1984/05/01. doi: 10.1111/j.1558-5646.1984.tb00317.x 28555975.

38. Stanley CE Jr., Kulathinal RJ. Genomic signatures of domestication on neurogenetic genes in Drosophila melanogaster. BMC Evol Biol. 2016;16:6. Epub 2016/01/06. doi: 10.1186/s12862-015-0580-1 26728183; PubMed Central PMCID: PMC4700609.

39. Castagnone-Sereno P, Mulet K, Danchin EGJ, Koutsovoulos GD, Karaulic M, Da Rocha M, et al. Gene copy number variations as signatures of adaptive evolution in the parthenogenetic, plant-parasitic nematode Meloidogyne incognita. Mol Ecol. 2019;28(10):2559–72. Epub 2019/04/10. doi: 10.1111/mec.15095 30964953.

40. Elde NC, Child SJ, Eickbush MT, Kitzman JO, Rogers KS, Shendure J, et al. Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses. Cell. 2012;150(4):831–41. Epub 2012/08/21. doi: 10.1016/j.cell.2012.05.049 22901812; PubMed Central PMCID: PMC3499626.

41. Farslow JC, Lipinski KJ, Packard LB, Edgley ML, Taylor J, Flibotte S, et al. Rapid Increase in frequency of gene copy-number variants during experimental evolution in Caenorhabditis elegans. BMC Genomics. 2015;16:1044. Epub 2015/12/10. doi: 10.1186/s12864-015-2253-2 26645535; PubMed Central PMCID: PMC4673709.

42. Lauer S, Avecilla G, Spealman P, Sethia G, Brandt N, Levy SF, et al. Single-cell copy number variant detection reveals the dynamics and diversity of adaptation. PLoS Biol. 2018;16(12):e3000069. Epub 2018/12/19. doi: 10.1371/journal.pbio.3000069 30562346; PubMed Central PMCID: PMC6298651.

43. Lauer S, Gresham D. An evolving view of copy number variants. Curr Genet. 2019. Epub 2019/05/12. doi: 10.1007/s00294-019-00980-0 31076843.

44. Venkataram S, Dunn B, Li Y, Agarwala A, Chang J, Ebel ER, et al. Development of a comprehensive genotype-to-fitness map of adaptation-driving mutations in yeast. Cell. 2016;166(6):1585–96. e22. doi: 10.1016/j.cell.2016.08.002 27594428

45. Vergara IA, Mah AK, Huang JC, Tarailo-Graovac M, Johnsen RC, Baillie DL, et al. Polymorphic segmental duplication in the nematode Caenorhabditis elegans. BMC Genomics. 2009;10:329. Epub 2009/07/23. doi: 10.1186/1471-2164-10-329 19622155; PubMed Central PMCID: PMC2728738.

46. Konrad A, Flibotte S, Taylor J, Waterston RH, Moerman DG, Bergthorsson U, et al. Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2018;115(28):7386–91. Epub 2018/06/27. doi: 10.1073/pnas.1801930115 29941601; PubMed Central PMCID: PMC6048555.

47. Yoshimura J, Ichikawa K, Shoura MJ, Artiles KL, Gabdank I, Wahba L, et al. Recompleting the Caenorhabditis elegans genome. Genome Res. 2019;29(6):1009–22. Epub 2019/05/28. doi: 10.1101/gr.244830.118 31123080; PubMed Central PMCID: PMC6581061.

48. Kim C, Kim J, Kim S, Cook DE, Evans KS, Andersen EC, et al. Long-read sequencing reveals intra-species tolerance of substantial structural variations and new subtelomere formation in C. elegans. Genome Res. 2019;29(6):1023–35. Epub 2019/05/28. doi: 10.1101/gr.246082.118 31123081; PubMed Central PMCID: PMC6581047.

49. Sterken MG, Snoek LB, Kammenga JE, Andersen EC. The laboratory domestication of Caenorhabditis elegans. Trends Genet. 2015;31(5):224–31. Epub 2015/03/26. doi: 10.1016/j.tig.2015.02.009 25804345; PubMed Central PMCID: PMC4417040.

50. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77(1):71–94. Epub 1974/05/01. 4366476; PubMed Central PMCID: PMC1213120.

51. McGrath PT, Xu Y, Ailion M, Garrison JL, Butcher RA, Bargmann CI. Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature. 2011;477(7364):321–5. Epub 2011/08/19. doi: 10.1038/nature10378 21849976; PubMed Central PMCID: PMC3257054.

52. de Bono M, Bargmann CI. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell. 1998;94(5):679–89. Epub 1998/09/19. doi: 10.1016/s0092-8674(00)81609-8 9741632.

53. Duveau F, Felix MA. Role of pleiotropy in the evolution of a cryptic developmental variation in Caenorhabditis elegans. PLoS Biol. 2012;10(1):e1001230. Epub 2012/01/12. doi: 10.1371/journal.pbio.1001230 22235190; PubMed Central PMCID: PMC3250502.

54. Large EE, Xu W, Zhao Y, Brady SC, Long L, Butcher RA, et al. Selection on a Subunit of the NURF Chromatin Remodeler Modifies Life History Traits in a Domesticated Strain of Caenorhabditis elegans. PLoS Genet. 2016;12(7):e1006219. Epub 2016/07/29. doi: 10.1371/journal.pgen.1006219 27467070; PubMed Central PMCID: PMC4965130.

55. McGrath PT, Rockman MV, Zimmer M, Jang H, Macosko EZ, Kruglyak L, et al. Quantitative mapping of a digenic behavioral trait implicates globin variation in C. elegans sensory behaviors. Neuron. 2009;61(5):692–9. Epub 2009/03/17. doi: 10.1016/j.neuron.2009.02.012 19285466; PubMed Central PMCID: PMC2772867.

56. Zhao Y, Long L, Xu W, Campbell RF, Large EE, Greene JS, et al. Changes to social feeding behaviors are not sufficient for fitness gains of the Caenorhabditis elegans N2 reference strain. Elife. 2018;7. Epub 2018/10/18. doi: 10.7554/eLife.38675 30328811; PubMed Central PMCID: PMC6224195.

57. Xu W, Long L, Zhao Y, Stevens L, Felipe I, Munoz J, et al. Evolution of Yin and Yang isoforms of a chromatin remodeling subunit precedes the creation of two genes. eLife. 2019;8:e48119. doi: 10.7554/eLife.48119 31498079

58. de Bono M, Tobin DM, Davis MW, Avery L, Bargmann CI. Social feeding in Caenorhabditis elegans is induced by neurons that detect aversive stimuli. Nature. 2002;419(6910):899–903. Epub 2002/11/01. doi: 10.1038/nature01169 12410303; PubMed Central PMCID: PMC3955269.

59. Gray JM, Karow DS, Lu H, Chang AJ, Chang JS, Ellis RE, et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature. 2004;430(6997):317–22. Epub 2004/06/29. doi: 10.1038/nature02714 15220933.

60. Flavell SW, Pokala N, Macosko EZ, Albrecht DR, Larsch J, Bargmann CI. Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C. elegans. Cell. 2013;154(5):1023–35. doi: 10.1016/j.cell.2013.08.001 23972393

61. Lee JI, Dhakal BK, Lee J, Bandyopadhyay J, Jeong SY, Eom SH, et al. The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin. Journal of molecular biology. 2003;328(1):147–56. doi: 10.1016/s0022-2836(03)00237-7 12684004

62. Tyson JR, O'Neil NJ, Jain M, Olsen HE, Hieter P, Snutch TP. MinION-based long-read sequencing and assembly extends the Caenorhabditis elegans reference genome. Genome Res. 2018;28(2):266–74. Epub 2017/12/24. doi: 10.1101/gr.221184.117 29273626; PubMed Central PMCID: PMC5793790.

63. Jänes J, Dong Y, Schoof M, Serizay J, Appert A, Cerrato C, et al. Chromatin accessibility dynamics across C. elegans development and ageing. Elife. 2018;7:e37344. doi: 10.7554/eLife.37344 30362940

64. Araya CL, Kawli T, Kundaje A, Jiang L, Wu B, Vafeados D, et al. Regulatory analysis of the C. elegans genome with spatiotemporal resolution. Nature. 2014;512(7515):400. doi: 10.1038/nature13497 25164749

65. Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, et al. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science. 2010;330(6012):1775–87. doi: 10.1126/science.1196914 21177976

66. Li W, Bell HW, Ahnn J, Lee SK. Regulator of Calcineurin (RCAN-1) Regulates Thermotaxis Behavior in Caenorhabditis elegans. J Mol Biol. 2015;427(22):3457–68. Epub 2015/08/02. doi: 10.1016/j.jmb.2015.07.017 26232604.

67. Itani OA, Flibotte S, Dumas KJ, Moerman DG, Hu PJ. Chromoanasynthetic genomic rearrangement identified in a N-ethyl-N-nitrosourea (ENU) mutagenesis screen in Caenorhabditis elegans. G3: Genes, Genomes, Genetics. 2016;6(2):351–6.

68. Innan H, Kondrashov F. The evolution of gene duplications: classifying and distinguishing between models. Nat Rev Genet. 2010;11(2):97–108. Epub 2010/01/07. doi: 10.1038/nrg2689 20051986.

69. Clark AG. Invasion and maintenance of a gene duplication. Proc Natl Acad Sci U S A. 1994;91(8):2950–4. Epub 1994/04/12. doi: 10.1073/pnas.91.8.2950 8159686; PubMed Central PMCID: PMC43492.

70. Lynch M, Force A. The probability of duplicate gene preservation by subfunctionalization. Genetics. 2000;154(1):459–73. Epub 2000/01/11. 10629003; PubMed Central PMCID: PMC1460895.

71. Neelsen KJ, Lopes M. Replication fork reversal in eukaryotes: from dead end to dynamic response. Nature Reviews Molecular Cell Biology. 2015;16(4):207. doi: 10.1038/nrm3935 25714681

72. Polleys EJ, House NC, Freudenreich CH. Role of recombination and replication fork restart in repeat instability. DNA repair. 2017;56:156–65. doi: 10.1016/j.dnarep.2017.06.018 28641941

73. Kugelberg E, Kofoid E, Andersson DI, Lu Y, Mellor J, Roth FP, et al. The tandem inversion duplication in Salmonella enterica: selection drives unstable precursors to final mutation types. Genetics. 2010;185(1):65–80. doi: 10.1534/genetics.110.114074 20215473

74. Pradhan S, Quilez S, Homer K, Hendricks M. Environmental programming of adult foraging behavior in C. elegans. Current Biology. 2019;29(17):2867–79. e4. doi: 10.1016/j.cub.2019.07.045 31422888

75. Rhoades JL, Nelson JC, Nwabudike I, Stephanie KY, McLachlan IG, Madan GK, et al. ASICs Mediate Food Responses in an Enteric Serotonergic Neuron that Controls Foraging Behaviors. Cell. 2019;176(1–2):85–97. e14. doi: 10.1016/j.cell.2018.11.023 30580965

76. Fuentes JJ, Genesca L, Kingsbury TJ, Cunningham KW, Perez-Riba M, Estivill X, et al. DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Hum Mol Genet. 2000;9(11):1681–90. Epub 2000/06/22. doi: 10.1093/hmg/9.11.1681 10861295.

77. Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature. 2006;441(7093):595–600. Epub 2006/03/24. doi: 10.1038/nature04678 16554754.

78. Martin KR, Corlett A, Dubach D, Mustafa T, Coleman HA, Parkington HC, et al. Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory. Hum Mol Genet. 2012;21(13):3025–41. Epub 2012/04/19. doi: 10.1093/hmg/dds134 22511596.

79. Li W, Choi T-W, Ahnn J, Lee S-K. Allele-Specific Phenotype Suggests a Possible Stimulatory Activity of RCAN-1 on Calcineurin in Caenorhabditis elegans. Molecules and cells. 2016;39(11):827. doi: 10.14348/molcells.2016.0222 27871170

80. Arribere JA, Bell RT, Fu BX, Artiles KL, Hartman PS, Fire AZ. Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans. Genetics. 2014;198(3):837–46. Epub 2014/08/28. doi: 10.1534/genetics.114.169730 25161212; PubMed Central PMCID: PMC4224173.

81. Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. bioinformatics. 2009;25(14):1754–60. doi: 10.1093/bioinformatics/btp324 19451168

82. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25(16):2078–9. doi: 10.1093/bioinformatics/btp352 19505943

83. http://broadinstitute.github.io/picard/index.html.

84. Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv preprint arXiv:12073907. 2012.

85. Cingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly. 2012;6(2):80–92. doi: 10.4161/fly.19695 22728672

86. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nature biotechnology. 2011;29(1):24. doi: 10.1038/nbt.1754 21221095

87. Seibt KM, Schmidt T, Heitkam T. FlexiDot: highly customizable, ambiguity-aware dotplots for visual sequence analyses. Bioinformatics. 2018;34(20):3575–7. Epub 2018/05/16. doi: 10.1093/bioinformatics/bty395 29762645.

88. Varet H, Brillet-Guéguen L, Coppée J-Y, Dillies M-A. SARTools: a DESeq2-and edgeR-based R pipeline for comprehensive differential analysis of RNA-Seq data. PLoS One. 2016;11(6):e0157022. doi: 10.1371/journal.pone.0157022 27280887

89. Anders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166–9. doi: 10.1093/bioinformatics/btu638 25260700

90. Chen Y, Lun AT, Smyth GK. Differential expression analysis of complex RNA-seq experiments using edgeR. Statistical analysis of next generation sequencing data: Springer; 2014. p. 51–74.

91. Lee H, Kim SA, Coakley S, Mugno P, Hammarlund M, Hilliard MA, et al. A multi-channel device for high-density target-selective stimulation and long-term monitoring of cells and subcellular features in C. elegans. Lab on a Chip. 2014;14(23):4513–22. doi: 10.1039/c4lc00789a 25257026

92. Evans KS, Brady SC, Bloom JS, Tanny RE, Cook DE, Giuliani SE, et al. Shared genomic regions underlie natural variation in diverse toxin responses. Genetics. 2018;210(4):1509–25. doi: 10.1534/genetics.118.301311 30341085

93. Garcia-Gonzalez AP, Ritter AD, Shrestha S, Andersen EC, Yilmaz LS, Walhout AJM. Bacterial Metabolism Affects the C. elegans Response to Cancer Chemotherapeutics. Cell. 2017;169(3):431–41 e8. Epub 2017/04/22. doi: 10.1016/j.cell.2017.03.046 28431244; PubMed Central PMCID: PMC5484065.

94. Shimko TC, Andersen EC. COPASutils: an R package for reading, processing, and visualizing data from COPAS large-particle flow cytometers. PLoS One. 2014;9(10):e111090. Epub 2014/10/21. doi: 10.1371/journal.pone.0111090 25329171; PubMed Central PMCID: PMC4203834.

95. Broman KW, Sen S. A Guide to QTL Mapping with R/qtl: Springer; 2009.

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Genetika Reprodukční medicína

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PLOS Genetics


2020 Číslo 2

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