Exploring the Complexity of the HIV-1 Fitness Landscape
Although fitness landscapes are central to evolutionary theory, so far no biologically realistic examples for large-scale fitness landscapes have been described. Most currently available biological examples are restricted to very few loci or alleles and therefore do not capture the high dimensionality characteristic of real fitness landscapes. Here we analyze large-scale fitness landscapes that are based on predictive models for in vitro replicative fitness of HIV-1. We find that these landscapes are characterized by large correlation lengths, considerable neutrality, and high ruggedness and that these properties depend only weakly on whether fitness is measured in the absence or presence of different antiretrovirals. Accordingly, adaptive processes on these landscapes depend sensitively on the initial conditions. While the relative extent to which mutations affect fitness on their own (main effects) or in combination with other mutations (epistasis) is a strong determinant of these properties, the fitness landscape of HIV-1 is considerably less rugged, less neutral, and more correlated than expected from the distribution of main effects and epistatic interactions alone. Overall this study confirms theoretical conjectures about the complexity of biological fitness landscapes and the importance of the high dimensionality of the genetic space in which adaptation takes place.
Vyšlo v časopise:
Exploring the Complexity of the HIV-1 Fitness Landscape. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002551
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002551
Souhrn
Although fitness landscapes are central to evolutionary theory, so far no biologically realistic examples for large-scale fitness landscapes have been described. Most currently available biological examples are restricted to very few loci or alleles and therefore do not capture the high dimensionality characteristic of real fitness landscapes. Here we analyze large-scale fitness landscapes that are based on predictive models for in vitro replicative fitness of HIV-1. We find that these landscapes are characterized by large correlation lengths, considerable neutrality, and high ruggedness and that these properties depend only weakly on whether fitness is measured in the absence or presence of different antiretrovirals. Accordingly, adaptive processes on these landscapes depend sensitively on the initial conditions. While the relative extent to which mutations affect fitness on their own (main effects) or in combination with other mutations (epistasis) is a strong determinant of these properties, the fitness landscape of HIV-1 is considerably less rugged, less neutral, and more correlated than expected from the distribution of main effects and epistatic interactions alone. Overall this study confirms theoretical conjectures about the complexity of biological fitness landscapes and the importance of the high dimensionality of the genetic space in which adaptation takes place.
Zdroje
1. WrightS 1931 Evolution in Mendelian Populations. Genetics 16 97 159
2. CollinsJAThompsonMGPaintsilERickettsMGedziorJ 2004 Competitive Fitness of Nevirapine-Resistant Human Immunodeficiency Virus Type 1 Mutants. J Virol 78 603 611
3. DeforcheKCamachoRVan LaethemKLemeyPRambautA 2008 Estimation of an in vivo fitness landscape experienced by HIV-1 under drug selective pressure useful for prediction of drug resistance evolution during treatment. Bioinformatics 24 34 41
4. PoelwijkFJKivietDJWeinreichDMTansSJ 2007 Empirical fitness landscapes reveal accessible evolutionary paths. Nature 445 383 386
5. WeinreichDMDelaneyNFDePristoMAHartlDL 2006 Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins. Science 312 111 114
6. WhitlockMCBourguetD 2000 Factors affecting the genetic load in Drosophila: synergistic epistasis and correlations among fitness components. Evolution 54 1654 1660
7. FrankeJKlozerAde VisserJAKrugJ Evolutionary accessibility of mutational pathways. PLoS Comput Biol 7 e1002134 doi:10.1371/journal.pcbi.1002134
8. O'MaillePEMaloneADellasNAndes HessBJrSmentekL 2008 Quantitative exploration of the catalytic landscape separating divergent plant sesquiterpene synthases. Nat Chem Biol 4 617 623
9. FontanaWStadlerPFBornberg-BauerEGGriesmacherTHofackerIL 1993 RNA folding and combinatory landscapes. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 47 2083 2099
10. PittJNFerre-DAmareAR Rapid Construction of Empirical RNA Fitness Landscapes. Science 330 376 379
11. LunzerMMillerSPFelsheimRDeanAM 2005 The Biochemical Architecture of an Ancient Adaptive Landscape. Science 310 499 501
12. KauffmanSLevinS 1987 Towards a general theory of adaptive walks on rugged landscapes. J Theor Biol 128 11 45
13. WeinbergerE 1990 Correlated and uncorrelated fitness landscapes and how to tell the difference. Biological Cybernetics 63 325 336
14. van NimwegenE 2006 Epidemiology. Influenza escapes immunity along neutral networks. Science 314 1884 1886
15. FontanaWSchusterP 1998 Continuity in evolution: on the nature of transitions. Science 280 1451 1455
16. KimuraM 1983 The neutral theory of molecular evolution.: Cambridge University Press
17. KoelleKCobeySGrenfellBPascualM 2006 Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans. Science 314 1898 1903
18. GavriletsS 2004 Fitness Landscapes and the Origin of Species: Princeton University Press
19. BonhoefferSChappeyCParkinNTWhitcombJMPetropoulosCJ 2004 Evidence for positive epistasis in HIV-1. Science 306 1547 1550
20. CostanzoMBaryshnikovaABellayJKimYSpearED The genetic landscape of a cell. Science 327 425 431
21. HinkleyTMartinsJChappeyCHaddadMStawiskiE 2011 A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase. Nat Genet 43 487 489
22. JohnsonVABrun-VezinetFClotetBGunthardHFKuritzkesDR 2010 Update of the drug resistance mutations in HIV-1: December 2010. Top HIV Med 18 156 163
23. Martinez-CajasJLWainbergMA 2007 Protease inhibitor resistance in HIV-infected patients: molecular and clinical perspectives. Antiviral Res 76 203 221
24. DoyonLTremblaySBourgonLWardropECordingleyMG 2005 Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir. Antiviral Res 68 27 35
25. OttoSPBartonNH 2001 Selection for recombination in small populations. Evolution 55 1921 1931
26. KeightleyPDOttoSP 2006 Interference among deleterious mutations favours sex and recombination in finite populations. Nature 443 89 92
27. FontanaWKoningsDAMStadlerPFSchusterP 1993 Statistics of Rna Secondary Structures. Biopolymers 33 1389 1404
28. KouyosRDvon WylVHinkleyTPetropoulosCJHaddadM 2011 Assessing predicted HIV-1 replicative capacity in a clinical setting. PLoS Pathog 7 e1002321 doi:10.1371/journal.ppat.1002321
29. PetropoulosCJParkinNTLimoliKLLieYSWrinT 2000 A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob Agents Chemother 44 920 928
30. MayerJEMontrollE 1941 Molecular distribution. Journal of Chemical Physics 9 2 16
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 3
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