#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Pervasive Cryptic Epistasis in Molecular Evolution


The functional effects of most amino acid replacements accumulated during molecular evolution are unknown, because most are not observed naturally and the possible combinations are too numerous. We created 168 single mutations in wild-type Escherichia coli isopropymalate dehydrogenase (IMDH) that match the differences found in wild-type Pseudomonas aeruginosa IMDH. 104 mutant enzymes performed similarly to E. coli wild-type IMDH, one was functionally enhanced, and 63 were functionally compromised. The transition from E. coli IMDH, or an ancestral form, to the functional wild-type P. aeruginosa IMDH requires extensive epistasis to ameliorate the combined effects of the deleterious mutations. This result stands in marked contrast with a basic assumption of molecular phylogenetics, that sites in sequences evolve independently of each other. Residues that affect function are scattered haphazardly throughout the IMDH structure. We screened for compensatory mutations at three sites, all of which lie near the active site and all of which are among the least active mutants. No compensatory mutations were found at two sites indicating that a single site may engage in compound epistatic interactions. One complete and three partial compensatory mutations of the third site are remote and lie in a different domain. This demonstrates that epistatic interactions can occur between distant (>20Å) sites. Phylogenetic analysis shows that incompatible mutations were fixed in different lineages.


Vyšlo v časopise: Pervasive Cryptic Epistasis in Molecular Evolution. PLoS Genet 6(10): e32767. doi:10.1371/journal.pgen.1001162
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001162

Souhrn

The functional effects of most amino acid replacements accumulated during molecular evolution are unknown, because most are not observed naturally and the possible combinations are too numerous. We created 168 single mutations in wild-type Escherichia coli isopropymalate dehydrogenase (IMDH) that match the differences found in wild-type Pseudomonas aeruginosa IMDH. 104 mutant enzymes performed similarly to E. coli wild-type IMDH, one was functionally enhanced, and 63 were functionally compromised. The transition from E. coli IMDH, or an ancestral form, to the functional wild-type P. aeruginosa IMDH requires extensive epistasis to ameliorate the combined effects of the deleterious mutations. This result stands in marked contrast with a basic assumption of molecular phylogenetics, that sites in sequences evolve independently of each other. Residues that affect function are scattered haphazardly throughout the IMDH structure. We screened for compensatory mutations at three sites, all of which lie near the active site and all of which are among the least active mutants. No compensatory mutations were found at two sites indicating that a single site may engage in compound epistatic interactions. One complete and three partial compensatory mutations of the third site are remote and lie in a different domain. This demonstrates that epistatic interactions can occur between distant (>20Å) sites. Phylogenetic analysis shows that incompatible mutations were fixed in different lineages.


Zdroje

1. DeanAM

ThorntonJW

2007 Mechanistic approaches to the study of evolution: the functional synthesis. Nat Rev Genet 8 675 688

2. FelsensteinJ

2004 Inferring phylogenies Sunderland Sinaur Assoc Inc

3. NeiM

KumarS

2000 Molecular evolution and phylogenetics Oxford Oxford University Press

4. SmithNG

Eyre-WalkerA

2002 Adaptive protein evolution in Drosophila. Nature 415 1022 1024

5. CharlesworthJ

Eyre-WalkerA

2006 The rate of adaptive evolution in enteric bacteria. Mol Biol Evol 23 1348 1356

6. SawyerSA

KulathinalRJ

BustamanteCD

HartlDL

2003 Bayesian analysis suggests that most amino acid replacements in Drosophila are driven by positive selection. J Mol Evol 57 154 164

7. HughesAL

2008 Near neutrality: leading edge of the neutral theory of molecular evolution. Ann NY Acad Sci 1133 162 179

8. DePristoMA

WeinreichDM

HartlDL

2007 Missense meanderings in sequences space: a biophysical view of protein evolution. Nat Rev Genet 6 678 687

9. PresgravesDC

2010 The molecular evolutionary basis of species formation. Nat Rev Genet 11 175 180

10. BartonNH

CharlesworthB

1998 Why sex and recombination? Science 281 1986 1990

11. KondrashovAS

1988 Deleterious mutations and the evolution of sexual reproduction. Nature 336 435 440

12. KacserH

BurnsJA

1981 The molecular basis of dominance. Genetics 97 639 666

13. JasnosL

KoronaM

2007 Epistatic buffering of fitness loss in yeast double deletion strains. Nat Genet 39 550 554

14. CordellHJ

2009 Detecting gene-gene interactions that underlie human diseases. Nat Rev Genet 10 392 404

15. ZuckerkandlE

1963 Perspectives in molecular anthropology.

WashburnSL

Classification and human evolution Chicago Aldine 243 272

16. FitchWM

MarkowitzE

1970 An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution. Biochem Genet 4 579 593

17. KorberBT

FarberRM

WolpertDH

LapedesAS

1993 Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis. Proc Natl Acad Sci USA 90 7176 7180

18. GöbelU

SanderC

SchneiderR

Valencia

1994 A Correlated mutations and residue contacts in proteins. Proteins 18 309 317

19. ShindyalovIN

KolchanovNA

SanderC

1994 Can three-dimensional contacts in protein structures be predicted by analysis of correlated mutations? Protein Eng 7 349 358

20. TaylorWR

FloresTP

OrengoCA

1994 Multiple protein structure alignment. Protein Sci 3 1858 1870

21. LocklessSW

RanganathanR

1999 Evolutionarily conserved pathways of energetic connectivity in protein families. Science 286 295 299

22. PritchardL

BladonPMO

MitchellJJ

DuftonM

2001 Evaluation of a novel method for the identification of coevolving protein residues. Protein Eng 14 549 555

23. ValdarWS

2002 Scoring residue conservation. Proteins 48 227 241

24. SüelGM

LocklessSW

WallMA

RanganathanR

2003 Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nat Struct Biol 10 59 69

25. SocolichM

LocklessSW

RussWP

LeeH

GardnerKH

2005 Evolutionary information for specifying a protein fold. Nature 437 512 518

26. RussWP

LoweryDM

MishraP

YaffeMB

RanganathanR

2005 Natural-like function in artificial WW domains. Nature 437 579 583

27. GloorGB

MartinLC

WahlLM

DunnSD

2005 Mutual information in protein multiple sequence alignments reveals two classes of coevolving positions. Biochemistry 44 7156 7165

28. AnéC

BurleighJG

McMahonMM

SandersonMJ

2005 Covarion structure in plastid genome evolution: a new statistical test. Mol Biol Evol 22 914 924

29. WangK

SamudralaR

2006 Incorporating background frequency improves entropy- based residue conservation measures. BMC Bioinformatics 17 385

30. TuffleyC

SteelMA

1997 Modelling the covarion hypothesis of nucleotide substitution. Math Biosci 147 63 91

31. LockhartPJ

SteelMA

BarbrookAC

HusonDH

CharlestonMA

1998 A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages. Mol Biol Evol 15 1183 1188

32. PollockDD

TaylorWR

GoldmanN

1999 Coevolving protein residues: Maximum likelihood identification and relationship to structure. J Mol Biol 287 187 198 (1999)

33. GaltierN

2001 Maximum-likelihood phylogenetic analysis under a covarion-like model. Mol Biol Evol 18 866 873

34. HuelsenbeckJP

2002 Testing a covariotide model of DNA substitution. Mol Biol Evol 19 698 707

35. DutheilJ

PupkoT

Jean-MarieA

GaltierN

2005 A model-based approach for detecting coevolving positions in a molecule. Mol Biol Evol 22 1919 1928

36. FaresMA

TraversSAA

2006 A Novel Method for detecting intramolecular coevolution: Adding a further dimension to selective constraints analyses. Genetics 173 9 23

37. WangHC

SpencerM

SuskoE

RogerAJ

2007 Testing for covarion-like evolution in protein sequences. Mol Biol Evol 24 294 305

38. RodrigueN

KleinmanCL

PhilippeH

LartillotN

2009 Computational methods for evaluating phylogenetic models of coding sequence evolution with dependence between codons. Mol Biol Evol 26 1663 1676

39. DeanAM

GoldingGB

2000 Enzyme evolution explained (sort of).

AltmanRB

DunkerAK

HunterL

LauderdaleK

KleinTE

The Pacific symposium on bioinformatics 2000: Singapore World Scientific

40. DeanAM

NeuhauserC

GrenierC

GoldingGB

2002 The pattern of amino acid replacements in α/β-barrels. Mol Biol Evol 19 1846 1864

41. KondrashovAS

SunyaevS

KondrashovFA

2002 Dobzhansky-Muller incompatibilities in protein evolution. Proc Natl Acad Sci USA 99 14878 14883

42. KulathinalRJ

BettencourtBR

HartlDL

2004 Compensated deleterious mutations in insect genomes. Science 306 1553 1554

43. GloorGB

TyagiG

AbrassartDM

KingstonAJ

FernandesAD

2010 Functionally compensating, coevolving positions are neither homoplasic nor conserved in clades. Mol Biol Evol 27 1181 1191

44. FisherA

ShiY

RitterA

FerrettiJA

Perez-LamboyG

2000 Functional correlation in amino acid residue mutations of yeast iso-2-cytochrome c that is consistent with the prediction of the concomitantly variable codon theory in cytochrome c evolution. Biochem Genet 38 181 200

45. MalcolmBA

WilsonKP

MatthewsBW

KirschJF

WilsonAC

1990 Ancestral lysozymes reconstructed, neutrality tested, and thermostability linked to hydrocarbon packing. Nature 345 86 89

46. WilsonKP

MalcomBA

MatthewsBW

1992 Structural and thermodynamic analysis of compensating mutations within the core of chicken egg white lysozyme. J Biol Chem 267 10842 10849

47. MateuMG

FershtA

1999 Mutually compensatory mutations during evolution of the tetramerization domain of tumor suppressor p53 lead to impaired hetero-oligomerization. Proc Natl Acad Sci USA 96 3595 3599

48. WeinreichDM

DelaneyNF

DePristoMA

HartlDL

2006 Darwinian evolution can follow only very mutational paths to fitter proteins. Science 312 111 114

49. BridghamJT

CarrollSM

ThorntonJW

2006 Evolution of hormone-receptor complexity by molecular exploitation. Science 312 97 101

50. YokoyamaS

TadaT

ZhangH

BrittL

2008 Elucidation of phenotypic adaptations: molecular analyses of dim-light vision proteins in vertebrates. Proc Natl Acad Sci USA 105 13480 13485

51. FieldSF

MatzMV

2010 Retracing evolution of red fluorescence in GFP-like proteins from Faviina corals. Mol Biol Evol 27 225 233

52. StryerL

1995 Biochemistry New York W. H. Freeman & Co

53. MillerSP

LunzerM

DeanAM

2006 Direct demonstration of an adaptive constraint. Science 314 458 461

54. ImadaK

SatoM

TanakaN

KatsubeY

MatsuuraY

1991 Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2Å resolution. J Mol Biol 222 725 738

55. WallonG

KrygerG

LovettST

OshimaT

RingeD

1997 Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus. J Mol Biol 266 1016 1031

56. ImadaK

InagakiK

MatsunamiH

KawaguchiH

TanakaH

1998 Structure of 3- isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 Å resolution: the role of Glu88 in the unique substrate-recognition mechanism. Structure 6 971 982

57. TsuchiyaD

SekiguchiT

TakenakaA

1997 Crystal structure of 3-isopropylmalate dehydrogenase from the moderate facultative thermophile, Bacillus coagulans: two strategies for thermostabilization of protein structures. J Biochem (Tokyo) 122 1092 104

58. LunzerM

MillerSP

FelsheimR

DeanAM

2005 The biochemical architecture of an ancient adaptive landscape. Science 310 499 501

59. SokalRR

RohlfFJ

1995 Biometry: The Principles and Practices of Statistics in Biological Research, 3rd ed NY WH Freeman

60. BenjaminiY

HochbergY

1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc B 57 289 300

61. FershtA

1998 Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding NY WH Freeman

62. HartlDL

DykhuizenDE

DeanAM

1985 Limits of adaptation: the evolution of selective neutrality. Genetics 111 655 674

63. KuikenKA

LymanCM

1948 The availability of amino acids in some foods. J Nutr 36 359 368

64. FitchWM

MarkowitzE

1970 An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution. Biochem Genet 4 579 593

65. OhtaT

1992 The nearly neutral theory of molecular evolution. Annu Rev Ecol Syst 23 263 286

66. PovolotskayaIS

KondrashovFA

2010 Sequence space and the ongoing expansion of the protein universe. Nature 465 922 927

67. GovindarajanS

NessJE

KimS

MundorffEC

MinshullJ

2003 Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation. J Mol Biol 328 1061 1069

68. OrrHA

1995 The population genetics of speciation: the evolution of hybrid incompatibilities. Genetics 139 1805 1813

69. OhtaT

KimuraM

1971 On the constancy of the evolutionary rate of cistrons. J Mol Evol 1 18 25

70. LangleyCH

FitchWM

1973 The constancy of evolution: a statistical analysis of α and β haemoglobins, cytochrome c, and point fibrinopeptide A.

MortonNE

Genetic Structure of Populations Honolulu University of Hawaii Press 246 262

71. LangleyCH

FitchWM

1974 An examination of the constancy of the rate of molecular evolution. J Mol Evol 3 161 177

72. GillespieJH

LangleyCH

1979 Are evolutionary rates really variable? J Mol Evol 13 27 34

73. GillespieJH

1991 The causes of molecular evolution Oxford, UK Oxford University Press

74. OhtaT

1995 Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory. J Mol Evol 40 56 63

75. BedfordT

WapinskiI

HartlDL

2008 Overdispersion of the molecular clock varies between yeast, Drosophila and mammals. Genetics 179 977 984

76. GillespieJH

1984 The molecular clock may be an episodic clock. Proc Natl Acad Sci USA 81 8009 8013

77. GillespieJH

1984 Molecular evolution over the mutational landscape. Evolution 38 1116 1129

78. TakahataN

1987 On the overdispersed molecular clock. Genetics 116 169 179

79. OhtaT

TachidaT

1990 Theoretical study of near neutrality. I. Heterozygosity and rate of mutant substitution. Genetics 126 219 229

80. TachidaH

1991 A study on a nearly neutral mutation model in finite populations. Genetics 128 183 192

81. IwasaY

1993 Overdispersed molecular evolution in constant environments. J Theor Biol 164 373 393

82. TakahataN

1991 Statistical models of the over-dispersed molecular clock. Theoret Popul Biol 39 329 344

83. ArakiH

TachidaH

1997 Bottleneck effect on evolutionary rate in the nearly neutral mutation model. Genetics 147 907 914

84. CutlerDJ

2000 Understanding the over-dispersed molecular clock. Genetics 154 1403 1417

85. KolaczkowskiB

ThorntonJW

2004 Performance of maximum parsimony and likelihood phylogenetics when evolution is heterogeneous. Nature 431 980 984

86. GruenheitN

LockhartPJ

SteelM

MartinW

2008 Difficulties in testing for covarion- like properties of sequences under the confounding influence of changing proportions of variable sites. Mol Biol Evol 25 1512 1520

87. WangHC

SuskoE

RogerAJ

2009 PROCOV: maximum likelihood estimation of protein phylogeny under covarion models and site-specific covarion patter analysis. BMC Evol Biol 9 225

88. RodrigueN

KleinmanCL

PhilippeH

LartillotN

2009 Computational methods for evaluating phylogenetic models of coding sequence evolution with dependence between codons. Mol Biol Evol 26 1663 1676

89. FelsensteinJ

2004 Inferring phylogenies Sunderland Sinaur Assoc Inc

90. KolaczkowskiB

ThorntonJW

2008 A mixed branch length model of heterotachy improves phylogenetic accuracy. Mol Biol Evol 25 1054 1066

91. KolaczkowskiB

ThorntonJW

2009 Long-branch attraction bias and inconsistency in Bayesian phylogenetics. PLoS ONE 4 e7891 doi:10.1371/journal.pone.0007891

92. WhelanS

2008 The genetic code can cause systematic bias in simple phylogenetic models. Phil Trans Roy Soc B 363 4003 4011

93. RokasA

KrügerD

CarrollSB

2005 Animal evolution and the molecular signature of radiations compressed in time. Science 310 1933 1938

94. RokasA

CarrollSB

2006 Bushes in the tree of life. PLoS Biol 4 e352 doi:10.1371/journal.pbio.0040352

95. SchönigerM

von HaeselerA

1994 A stochastic model for the evolution of autocorrelated DNA sequences. Mol Phylogenet Evol 3 240 247

96. WilliamsPD

PollockDD

BlackburneBP

GoldsteinRA

2006 Assessing the accuracy of ancestral protein reconstruction methods. PLoS Comput Biol 2 e69 doi:10.1371/journal.pcbi.0020069

97. TillierERM

CollinsRA

1995 Neighbor Joining and Maximum Likelihood with RNA sequences: addressing the interdependence of sites. Mol Biol Evol 12 7 15

98. Hanson-SmithV

KolaczkowskiB

ThorntonJW

2010 Robustness of ancestral sequence reconstruction to phylogenetic uncertainty. Mol Biol Evol 2010 Apr 5. [Epub ahead of print]

99. BridghamJT

OrtlundEA

ThorntonJW

2009 An epistatic ratchet constrains the direction of glucocorticoid receptor evolution. Nature 461 515 519

100. TokurikiN

StricherF

SerranoL

TawfikDS

2008 How protein stability and new functions trade off. PLoS Comput Biol 4 e1000002 doi:10.1371/journal.pcbi.1000002

101. StemmerWP

1994 Rapid evolution of a protein in vitro by DNA shuffling. Nature 370 389 391

102. BershteinS

GoldinK

TawfikDS

2008 Intense neutral drifts yield robust and evolvable consensus proteins. J Mol Biol 379 1029 1044

103. BabaT

AraT

HasegawaM

TakaiY

OkumuraY

2006 Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol Syst Biol 2 2006.0008

104. MillerJH

1992 A short course in bacterial genetics Cold Spring Harbor Cold Spring Harbor Laboratory Press

105. HanahanD

JesseeJ

BloomFR

1991 Plasmid transformation of E. coli and other bacteria. Methods Enzymol 204 63 113

106. New England Biolabs 1994 The NEB Transcript 6 7

107. Novagen 2009 User protocol TB506 Rev. A 0408

108. BradfordMM

1976 A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72 248 254

109. ThompsonJD

HigginsDG

GibsonTJ

1994 CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position- specific gap penalties and weight matrix choice. Nucleic Acids Res 22 4673 4680

110. GuexN

PeitschMC

1997 SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18 2714 2723

111. FelsensteinJ

1994 PHYLIP Version 3.5 Seattle University of Washington, WA

112. JonesDT

TaylorWR

ThorntonJM

1992 The rapid generation of mutation data matrices from protein sequences. Comp Appl Biosci 8 275 282

113. RonquistF

HuelsenbeckJP

2003 MRBAYES 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19 1572 1574

114. PupkoT

Pe'erI

GraurD

HasegawaM

FriedmanN

2002 A branch-and-bound algorithm for the inference of ancestral amino-acid sequences when the replacement rate varies among sites: application to the evolution of five gene families. Bioinformatics 18 1116 1123

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

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#