Selection on a Variant Associated with Improved Viral Clearance Drives Local, Adaptive Pseudogenization of Interferon Lambda 4 ()

English version České info

The genetic association with clearance of Hepatitis C virus (HCV) is one of the strongest and most elusive known associations with disease. The genetic variant more strongly associated with improved HCV clearance inactivates the recently discovered IFNL4 gene, which encodes for antiviral IFN-λ4 protein, and turns it into a polymorphic pseudogene. We show that functional IFN-λ4 is conserved and functionally important in mammals. In humans though the inactivating mutation appeared in Africa just before the out-of-Africa migration and quickly became advantageous, with the strength of selection (the degree of advantage) varying across human groups. In particular, selection became stronger out of Africa and was strongest in East Asia, raising the frequency of the pseudogene and resulting in the virtual loss of functional IFN-λ4 protein in several Asian populations. Although the environmental force driving selection is unknown, this process resulted in variable clearance of HCV in modern human populations. The complex selective history of IFNL4-inactivating allele has thus shaped present-day heterogeneity across populations not only in genetic variation, but also in relevant phenotypes and susceptibility to disease.

Vyšlo v časopise: Selection on a Variant Associated with Improved Viral Clearance Drives Local, Adaptive Pseudogenization of Interferon Lambda 4 (). PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004681
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004681

Souhrn

Zdroje

1. DonnellyRP, KotenkoSV (2010) Interferon-Lambda: A New Addition to an Old Family. Journal of Interferon & Cytokine Research 30: 555–564.

2. SheppardP, KindsvogelW, XuW, HendersonK, SchlutsmeyerS, et al. (2002) IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4: 63–68.

3. KotenkoSV, GallagherG, BaurinVV, Lewis-AntesA, ShenM, et al. (2002) IFN-θs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4: 69–77.

4. TanakaY, NishidaN, SugiyamaM, KurosakiM, MatsuuraK, et al. (2009) Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C. Nat Genet 41: 1105–1109.

5. ThomasDL, ThioCL, MartinMP, QiY, GeD, et al. (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461: 798–801.

6. GeD, FellayJ, ThompsonAJ, SimonJS, ShiannaKV, et al. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461: 399–401.

7. HanafiahKM, GroegerJ, FlaxmanAD, WiersmaST (2013) Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology 57: 1333–1342.

8. PerzJF, ArmstrongGL, FarringtonLA, HutinYJ, BellBP (2006) The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45: 529–538.

9. DillMT, DuongFH, VogtJE, BibertS, BochudP, et al. (2011) Interferon-Induced Gene Expression Is a Stronger Predictor of Treatment Response Than {IL28B} Genotype in Patients With Hepatitis C. Gastroenterology 140: 1021–1031.e10.

10. FukuharaT, TaketomiA, MotomuraT, OkanoS, NinomiyaA, et al. (2010) Variants in {IL28B} in Liver Recipients and Donors Correlate With Response to Peg-Interferon and Ribavirin Therapy for Recurrent Hepatitis C. Gastroenterology 139: 1577–1585.e3.

11. LanghansB, KupferB, BraunschweigerI, ArndtS, SchulteW, et al. (2011) Interferon-lambda serum levels in hepatitis C. J Hepatol 54: 859–865.

12. SugiyamaM, TanakaY, WakitaT, NakanishiM, MizokamiM (2011) Genetic variation of the IL-28B promoter affecting gene expression. PLoS One 6: e26620.

13. HondaM, SakaiA, YamashitaT, NakamotoY, MizukoshiE, et al. (2010) Hepatic {ISG} Expression Is Associated With Genetic Variation in Interleukin 28B and the Outcome of {IFN} Therapy for Chronic Hepatitis C. Gastroenterology 139: 499–509.

14. UrbanTJ, ThompsonAJ, BradrickSS, FellayJ, SchuppanD, et al. (2010) IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52: 1888–1896.

15. de CastellarnauM, AparicioE, PareraM, FrancoS, TuralC, et al. (2012) Deciphering the interleukin 28B variants that better predict response to pegylated interferon-α and ribavirin therapy in HCV/HIV-1 coinfected patients. PLoS One 7: e31016.

16. SmithKR, SuppiahV, O'ConnorK, BergT, WeltmanM, et al. (2011) Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort. Genome medicine 3: 57.

17. Prokunina-OlssonL, MuchmoreB, TangW, PfeifferRM, ParkH, et al. (2013) A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 45: 164.

18. HammingOJ, Terczyńska-DylaE, VieyresG, DijkmanR, JørgensenSE, et al. (2013) Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses. EMBO J

19. AkaP, KuniholmMH, PfeifferRM, WangAS, TangW, et al. (2013) Association of the IFNL4-ΔG Allele with Impaired Spontaneous Clearance of Hepatitis C Virus. Journal of Infectious Diseases 32: 3055–65 doi: 10.1038/emboj.2013.232

20. BibertS, RogerT, CalandraT, BochudM, CernyA, et al. (2013) IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 210: 1109–1116.

21. ManryJ, LavalG, PatinE, FornarinoS, ItanY, et al. (2011) Evolutionary genetic dissection of human interferons. J Exp Med 208: 2747–2759.

22. BeaumontMA, ZhangW, BaldingDJ (2002) Approximate Bayesian computation in population genetics. Genetics 162: 2025–2035.

23. PeterB, Huerta-SanchezE, NielsenR (2012) Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation. PLoS Genet 8: e1003011.

24. McVeanGA, Altshuler (Co-Chair)DM, Durbin (Co-Chair)RM, AbecasisGR, BentleyDR, et al. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56–65.

25. WeirS, CockerhamCC (1984) Estimating F-Statistics for the Analysis of Population Structure. Evolution 38: 1358.

26. SabetiPC, VarillyP, FryB, LohmuellerJ, HostetterE, et al. (2007) Genome-wide detection and characterization of positive selection in human populations. Nature 449: 913–918.

27. VoightBFAK, WenSA, PritchardXA, KJ (2006) A Map of Recent Positive Selection in the Human Genome. PLoS Biol 4: e72.

28. FayJC, WuCI (2000) Hitchhiking under positive Darwinian selection. Genetics 155: 1405.

29. di IulioJ, CiuffiA, FitzmauriceK, KelleherD, RotgerM, et al. (2011) Estimating the net contribution of interleukin-28B variation to spontaneous hepatitis C virus clearance. Hepatology 53: 1446–1454.

30. SuppiahV, MoldovanM, AhlenstielG, BergT, WeltmanM, et al. (2009) IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat Genet 41: 1100–1104.

31. FuW, AkeyJM (2013) Selection and Adaptation in the Human Genome. Annu Rev Genomics Hum Genet 14: 467–89 doi: 10.1146/annurev-genom-091212-153509

32. KassRE, RafteryAE (1995) Bayes factors. Journal of the american statistical association 90: 773–795.

33. Jeffreys H (1998) The theory of probability. Oxford University Press.

34. SheblFM, PfeifferRM, BuckettD, MuchmoreB, ChenS, et al. (2011) IL28B rs12979860 genotype and spontaneous clearance of hepatitis C virus in a multi-ethnic cohort of injection drug users: evidence for a supra-additive association. Journal of Infectious Diseases 204: 1843–1847 jir647.

35. FreemanA (2001) Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 34: 809–816.

36. BibertS, WojtowiczA, TafféP, ManuelO, BernasconiE, et al. (2014) The IFNL3/4 [DELTA]G variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients. AIDS [In Press].

37. TeijaroJR, NgC, LeeAM, SullivanBM, SheehanKCF, et al. (2013) Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling. Science 340: 207–211.

38. WilsonEB, YamadaDH, ElsaesserH, HerskovitzJ, DengJ, et al. (2013) Blockade of Chronic Type I Interferon Signaling to Control Persistent LCMV Infection. Science 340: 202–207.

39. OlsonMV (1999) When less is more: gene loss as an engine of evolutionary change. Am J Hum Genet 64: 18.

40. McLeanCY, RenoPL, PollenAA, BassanAI, CapelliniTD, et al. (2011) Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471: 216.

41. MacArthurDG, BalasubramanianS, FrankishA, HuangN, MorrisJ, et al. (2012) A Systematic Survey of Loss-of-Function Variants in Human Protein-Coding Genes. Science 335: 823–828.

42. MontgomerySB, GoodeD, KvikstadE, AlbersCA, ZhangZ, et al. (2013) The origin, evolution and functional impact of short insertion-deletion variants identified in 179 human genomes. Genome Res 23: 749–61 doi: 10.1101/gr.148718.112

43. YngvadottirB, XueY, SearleS, HuntS, DelgadoM, et al. (2009) A Genome-wide Survey of the Prevalence and Evolutionary Forces Acting on Human Nonsense {SNPs}. Am J Hum Genet 84: 224–234.

44. FrischmeyerPA, DietzHC (1999) Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 8: 1893–1900.

45. AndrésAM, DennisMY, KretzschmarWW, CannonsJL, Lee-LinSQ, et al. (2010) Balancing selection maintains a form of ERAP2 that undergoes nonsense-mediated decay and affects antigen presentation. PLoS Genet 6: e1001157.

46. HamblinMT, RienzoAD (2000) Detection of the Signature of Natural Selection in Humans: Evidence from the Duffy Blood Group Locus. Am J Hum Genet 66: 1669–1679.

47. WangXAG, ZhangWEA, Jianzhi (2006) Gene Losses during Human Origins. PLoS Biol 4: e52.

48. XueY, DalyA, YngvadottirB, LiuM, CoopG, et al. (2006) Spread of an inactive form of caspase-12 in humans is due to recent positive selection. The American Journal of Human Genetics 78: 659–670.

49. MacArthurDG, SetoJT, RafteryJM, QuinlanKG, HuttleyGA, et al. (2007) Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet 39: 1261–1265.

50. SeixasS, IvanovaN, FerreiraZ, RochaJ, VictorBL (2012) Loss and Gain of Function in SERPINB11: An Example of a Gene under Selection on Standing Variation, with Implications for Host-Pathogen Interactions. PLoS One 7: e32518.

51. TishkoffSA, ReedFA, RanciaroA, VoightBF, BabbittCC, et al. (2007) Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet 39: 31–40.

52. ThompsonJD, GibsonT, HigginsDG (2002) Multiple sequence alignment using ClustalW and ClustalX. Current protocols in bioinformatics Chapter 2. Unit 2.3. doi: 10.1002/0471250953.bi0203s00

53. WaterhouseAM, ProcterJB, MartinDM, ClampM, BartonGJ (2009) Jalview Version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25: 1189–1191.

54. YangZ (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24: 1586–1591.

55. PatenB, HerreroJ, FitzgeraldS, BealK, FlicekP, et al. (2008) Genome-wide nucleotide-level mammalian ancestor reconstruction. Genome Res 18: 1829–1843.

56. KvikstadEM, DuretL (2014) Strong Heterogeneity in Mutation Rate Causes Misleading Hallmarks of Natural Selection on Indel Mutations in the Human Genome. Mol Biol Evol 31: 23–36.

57. NielsenR (2005) Molecular signatures of natural selection. Annu Rev Genet 39: 197–218.

58. DanecekP, AutonA, AbecasisG, AlbersCA, BanksE, et al. (2011) The variant call format and VCFtools. Bioinformatics 27: 2156–2158.

59. GrossmanS, AndersenK, ShlyakhterI, TabriziS, WinnickiS, et al. (2013) Identifying Recent Adaptations in Large-Scale Genomic Data. Cell 152: 703–713.

60. FrazerKA, BallingerDG, CoxDR, HindsDA, StuveLL, et al. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449: 851–861.

61. Team RC (2011) R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2012. Open access available at: http://cran.r-project.org

62. HudsonRR (2002) Generating samples under a Wright–Fisher neutral model of genetic variation. Bioinformatics 18: 337–338.

63. GravelS, HennBM, GutenkunstRN, IndapAR, MarthGT, et al. (2011) Demographic history and rare allele sharing among human populations. Proceedings of the National Academy of Sciences 108: 11983–11988.

64. GutenkunstRNAH, WilliamsonRDA, BustamanteSHA, CarlosC (2009) Inferring the Joint Demographic History of Multiple Populations from Multidimensional SNP Frequency Data. PLoS Genet 5: e1000695.

65. EwingG, HermissonJ (2010) MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus. Bioinformatics 26: 2064–2065.

66. WegmannD, LeuenbergerC, NeuenschwanderS, ExcoffierL (2010) Abctoolbox: a versatile toolkit for approximate bayesian computations. BMC Bioinformatics 11: 116.

67. TajimaF (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123: 585.

68. ReynoldsJ, WeirBS, CockerhamCC (1983) Estimation of the coancestry coefficient: basis for a short-term genetic distance. Genetics 105: 767–779.

69. WegmannD, LeuenbergerC, ExcoffierL (2009) Efficient approximate Bayesian computation coupled with Markov chain Monte Carlo without likelihood. Genetics 182: 1207–1218.

70. TenenhausM (1998) La régression PLS: théorie et pratique. Editions Technip

71. BoulesteixA-L, StrimmerK (2007) Partial least squares: A versatile tool for the analysis of high-dimensional genomic data. Brief Bioinform 8: 32–44.

72. McFarlandAP, HornerSM, JarretA, JoslynRC, BindewaldE, et al. (2013) The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus–induced microRNAs. Nat Immunol 15: 72–79.