#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Histone Variant HTZ1 Shows Extensive Epistasis with, but Does Not Increase Robustness to, New Mutations


Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic variation. This result is typically interpreted as evidence that the disrupted gene normally increases robustness to mutations, as such robustness would allow cryptic variants to accumulate. However, revelation of cryptic genetic variation is not necessarily evidence that a mutationally robust state has been made less robust. Demonstrating a difference in robustness requires comparing the ability of each state (with the gene perturbed or intact) to suppress the effects of new mutations. Previous studies used strains in which the existing genetic variation had been filtered by selection. Here, we use mutation accumulation (MA) lines that have experienced minimal selection, to test the ability of histone H2A.Z (HTZ1) to increase robustness to mutations in the yeast Saccharomyces cerevisiae. HTZ1, a regulator of chromatin structure and gene expression, represents a class of genes implicated in mutational robustness. It had previously been shown to increase robustness of yeast cell morphology to fluctuations in the external or internal microenvironment. We measured morphological variation within and among 79 MA lines with and without HTZ1. Analysis of within-line variation confirms that HTZ1 increases microenvironmental robustness. Analysis of between-line variation shows the morphological effects of eliminating HTZ1 to be highly dependent on the line, which implies that HTZ1 interacts with mutations that have accumulated in the lines. However, lines without HTZ1 are, as a group, not more phenotypically diverse than lines with HTZ1 present. The presence of HTZ1, therefore, does not confer greater robustness to mutations than its absence. Our results provide experimental evidence that revelation of cryptic genetic variation cannot be assumed to be caused by loss of robustness, and therefore force reevaluation of prior claims based on that assumption.


Vyšlo v časopise: Histone Variant HTZ1 Shows Extensive Epistasis with, but Does Not Increase Robustness to, New Mutations. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003733
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003733

Souhrn

Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation. Prior studies identified genes that, when impaired, reveal previously cryptic genetic variation. This result is typically interpreted as evidence that the disrupted gene normally increases robustness to mutations, as such robustness would allow cryptic variants to accumulate. However, revelation of cryptic genetic variation is not necessarily evidence that a mutationally robust state has been made less robust. Demonstrating a difference in robustness requires comparing the ability of each state (with the gene perturbed or intact) to suppress the effects of new mutations. Previous studies used strains in which the existing genetic variation had been filtered by selection. Here, we use mutation accumulation (MA) lines that have experienced minimal selection, to test the ability of histone H2A.Z (HTZ1) to increase robustness to mutations in the yeast Saccharomyces cerevisiae. HTZ1, a regulator of chromatin structure and gene expression, represents a class of genes implicated in mutational robustness. It had previously been shown to increase robustness of yeast cell morphology to fluctuations in the external or internal microenvironment. We measured morphological variation within and among 79 MA lines with and without HTZ1. Analysis of within-line variation confirms that HTZ1 increases microenvironmental robustness. Analysis of between-line variation shows the morphological effects of eliminating HTZ1 to be highly dependent on the line, which implies that HTZ1 interacts with mutations that have accumulated in the lines. However, lines without HTZ1 are, as a group, not more phenotypically diverse than lines with HTZ1 present. The presence of HTZ1, therefore, does not confer greater robustness to mutations than its absence. Our results provide experimental evidence that revelation of cryptic genetic variation cannot be assumed to be caused by loss of robustness, and therefore force reevaluation of prior claims based on that assumption.


Zdroje

1. Wagner A. (2005) Robustness and evolvability in living systems. Princeton: Princeton University Press. 367 p.

2. MaselJ, SiegalML (2009) Robustness: Mechanisms and consequences. Trends Genet 25: 395–403.

3. GibsonG (2009) Decanalization and the origin of complex disease. Nat Rev Genet 10: 134–140.

4. WhitesellL, LindquistSL (2005) HSP90 and the chaperoning of cancer. Nat Rev Cancer 5: 761–772.

5. KitanoH (2007) Towards a theory of biological robustness. Mol Syst Biol 3: 137.

6. MaselJ (2006) Cryptic genetic variation is enriched for potential adaptations. Genetics 172: 1985–1991.

7. WagnerA (2008) Robustness and evolvability: A paradox resolved. Proc Biol Sci 275: 91–100.

8. HermissonJ, WagnerGP (2004) The population genetic theory of hidden variation and genetic robustness. Genetics 168: 2271–2284.

9. ScharlooW (1991) Canalization: Genetic and developmental aspects. Annual Review of Ecology and Systematics 22: 65–93.

10. SangsterTA, LindquistS, QueitschC (2004) Under cover: Causes, effects and implications of Hsp90-mediated genetic capacitance. Bioessays 26: 348–362.

11. WaddingtonCH (1952) Selection of the genetic basis for an acquired character. Nature 169: 625–626.

12. RutherfordSL, LindquistS (1998) Hsp90 as a capacitor for morphological evolution. Nature 396: 336–342.

13. QueitschC, SangsterTA, LindquistS (2002) Hsp90 as a capacitor of phenotypic variation. Nature 417: 618–624.

14. WaddingtonCH (1956) Genetic assimilation of the bithorax phenotype. Evolution 10: 1–13.

15. DworkinI (2005) Evidence for canalization of distal-less function in the leg of Drosophila melanogaster. Evol Dev 7: 89–100.

16. GibsonG, DworkinI (2004) Uncovering cryptic genetic variation. Nat Rev Genet 5: 681–690.

17. SpecchiaV, PiacentiniL, TrittoP, FantiL, D'AlessandroR, et al. (2010) Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons. Nature 463: 662–665.

18. SiegalML, MaselJ (2012) Hsp90 depletion goes wild. BMC Biol 10: 14.

19. GangarajuVK, YinH, WeinerMM, WangJ, HuangXA, et al. (2011) Drosophila piwi functions in Hsp90-mediated suppression of phenotypic variation. Nat Genet 43: 153–158.

20. MillozJ, DuveauF, Nuez I. FelixMA (2008) Intraspecific evolution of the intercellular signaling network underlying a robust developmental system. Genes Dev 22: 3064–3075.

21. DuveauF, FelixMA (2012) Role of pleiotropy in the evolution of a cryptic developmental variation in Caenorhabditis elegans. PLoS Biol 10: e1001230.

22. TrueHL, LindquistSL (2000) A yeast prion provides a mechanism for genetic variation and phenotypic diversity. Nature 407: 477–483.

23. JaroszDF, LindquistS (2010) Hsp90 and environmental stress transform the adaptive value of natural genetic variation. Science 330: 1820–1824.

24. HalfmannR, JaroszDF, JonesSK, ChangA, LancasterAK, et al. (2012) Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature 482: 363–368.

25. FreddolinoPL, GoodarziH, TavazoieS (2012) Fitness landscape transformation through a single amino acid change in the rho terminator. PLoS Genet 8: e1002744.

26. SuzukiY, NijhoutHF (2006) Evolution of a polyphenism by genetic accommodation. Science 311: 650–652.

27. BergerD, BauerfeindSS, BlanckenhornWU, SchaferMA (2011) High temperatures reveal cryptic genetic variation in a polymorphic female sperm storage organ. Evolution 65: 2830–2842.

28. KienleS, SommerRJ (2013) Cryptic variation in vulva development by cis-regulatory evolution of a HAIRY-binding site. Nat Commun 4: 1714.

29. TakahashiKH (2013) Multiple capacitors for natural genetic variation in Drosophila melanogaster. Molecular Ecology 22: 1356–1365.

30. GibsonG, van HeldenS (1997) Is function of the Drosophila homeotic gene Ultrabithorax canalized? Genetics 147: 1155–1168.

31. ElenaSF, LenskiRE (2001) Epistasis between new mutations and genetic background and a test of genetic canalization. Evolution 55: 1746–1752.

32. RemoldSK, LenskiRE (2001) Contribution of individual random mutations to genotype-by-environment interactions in Escherichia coli. Proc Natl Acad Sci U S A 98: 11388–11393.

33. LynchM, HillW (1986) Phenotypic evolution by neutral mutation. Evolution 40: 915–935.

34. LynchM (1988) The rate of polygenic mutation. Genet Res 51: 137–148.

35. BaerCF (2008) Quantifying the decanalizing effects of spontaneous mutations in rhabditid nematodes. Am Nat 172: 272–281.

36. JosephSB, HallDW (2004) Spontaneous mutations in diploid Saccharomyces cerevisiae: More beneficial than expected. Genetics 168: 1817–1825.

37. HallDW, MahmoudizadR, HurdAW, JosephSB (2008) Spontaneous mutations in diploid saccharomyces cerevisiae: Another thousand cell generations. Genet Res 90: 229–241.

38. KolodnerRD, PutnamCD, MyungK (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297: 552–557.

39. LynchM, SungW, MorrisK, CoffeyN, LandryCR, et al. (2008) A genome-wide view of the spectrum of spontaneous mutations in yeast. Proc Natl Acad Sci U S A 105: 9272–9277.

40. ZhangH, RobertsDN, CairnsBR (2005) Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123: 219–231.

41. LevySF, SiegalML (2008) Network hubs buffer environmental variation in saccharomyces cerevisiae. PLoS Biol 6: e264.

42. MeiklejohnCD, HartlDL (2002) A single mode of canalization. Trends in Ecology & Evolution 17: 468–473.

43. WagnerGP, BoothG, Bagheri-ChaichianH (1997) A population genetic theory of canalization. Evolution 51: 329–347.

44. TiroshI, ReikhavS, SigalN, AssiaY, BarkaiN (2010) Chromatin regulators as capacitors of interspecies variations in gene expression. Mol Syst Biol 6: 435.

45. VenancioTM, BalajiS, AravindL (2010) High-confidence mapping of chemical compounds and protein complexes reveals novel aspects of chemical stress response in yeast. Mol Biosyst 6: 175–181.

46. GibertJM, PeronnetF, SchlottererC (2007) Phenotypic plasticity in Drosophila pigmentation caused by temperature sensitivity of a chromatin regulator network. PLoS Genet 3: e30.

47. OhyaY, SeseJ, YukawaM, SanoF, NakataniY, et al. (2005) High-dimensional and large-scale phenotyping of yeast mutants. Proc Natl Acad Sci U S A 102: 19015–19020.

48. RobertsonA (1959) The sampling variance of the genetic correlation coefficient. Biometrics 15: 469–485.

49. Cockerham CC. (1963) Estimation of genetic variances. In: Hanson WD, Robertson HF, editors. Statistical Genetics and Plant Breeding. Washington: National Academy of Sciences National Research Council. pp. 53–93.

50. Van der LaanM, PollardK, BryanJ (2012) A new partitioning around medoids algorithm. J Statist Comput Simulation 73: 575–584.

51. CooperT, MorbyA, GunnA, SchneiderD (2006) Effect of random and hub gene disruptions on environmental and mutational robustness in Escherichia coli. BMC Genomics 7: 237.

52. CowenLE, LindquistS (2005) Hsp90 potentiates the rapid evolution of new traits: Drug resistance in diverse fungi. Science 309: 2185–2189.

53. MiltonCC, UlaneCM, RutherfordS (2006) Control of canalization and evolvability by Hsp90. PLoS ONE 1: e75.

54. SiegalML (2013) Crouching variation revealed. Molecular Ecology 22: 1187–1189.

55. Dujon B. (1981) Mitochondrial genetics and functions. In: Strathern J, Jones E, Broach J, editors. The Molecular Biology of the Yeast Saccharomyces. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. pp. 505–635.

56. Kassir Y, Simchen G. (1991) Monitoring meiosis and sporulation in Saccharomyces cerevisiae. In: Guthrie C, Fink GR, editors. Guide to yeast genetics and molecular biology. New York: Academic Press. pp. 94–110.

57. GietzRD, WoodsRA (2002) Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350: 87–96.

58. TuiteMF, CoxBS (2006) The [PSI+] prion of yeast: A problem of inheritance. Methods 39: 9–22.

59. BrachmannCB, DaviesA, CostGJ, CaputoE, LiJ, et al. (1998) Designer deletion strains derived from Saccharomyces cerevisiae S288C: A useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14: 115–132.

60. BoxG, CoxD (1964) An analysis of transformations (with discussion). Journal of the Royal Statistical Society B 26: 211–252.

61. OhnukiS, OkaS, NogamiS, OhyaY (2010) High-content, image-based screening for drug targets in yeast. PLoS One 5: e10177.

62. WatanabeM, WatanabeD, NogamiS, MorishitaS, OhyaY (2009) Comprehensive and quantitative analysis of yeast deletion mutants defective in apical and isotropic bud growth. Curr Genet 55: 365–380.

63. FraserHB, LevyS, ChavanA, ShahHB, PerezJC, et al. (2012) Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity. Genome Res 22: 1930–1939.

64. HadfieldJD (2010) MCMC Methods for Multi-Response Generalized Linear Mixed Models: The MCMCglmm R Package. J Stat Softw 33: 1–22.

65. AstlesPA, MooreAJ, PreziosiRF (2006) A comparison of methods to estimate cross-environment genetic correlations. J Evol Biol 19: 114–22.

66. LandryCR, LemosB, RifkinSA, DickinsonWJ, HartlDL (2007) Genetic properties influencing the evolvability of gene expression. Science 317: 118–121.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#