Selecting among three basic fitness landscape models: additive, multiplicative and stickbreaking

Fitness landscapes map genotypes to organismal fitness. Their topography depends on how mutational effects interact–epistasis–and is important for understanding evolutionary processes such as speciation, the rate of adaptation, the advantage of recombination, and predictability versus stochasticity of evolution. The growing amount of empirical data has made it possible to better test landscape models empirically. We argue that this endeavor will benefit from the development and use of meaningful null models against which to compare more complex models. Here we develop statistical and computational methods for fitting fitness data from mutation combinatorial networks to three simple models: additive, multiplicative and stickbreaking. We employ a Bayesian framework for doing model selection. Using simulations, we demonstrate that our methods work and we explore their statistical performance: bias, error, and the power to discriminate among models. We then illustrate our approach and its flexibility by analyzing several previously published datasets. An R-package that implements our methods is available in the CRAN repository under the name Stickbreaker.

[1]  Joshua R. Nahum,et al.  A tortoise–hare pattern seen in adapting structured and unstructured populations suggests a rugged fitness landscape in bacteria , 2015, Proceedings of the National Academy of Sciences.

[2]  A. Vincent,et al.  Modulation of Poliovirus Replicative Fitness in HeLa Cells by Deoptimization of Synonymous Codon Usage in the Capsid Region , 2006, Journal of Virology.

[3]  Nigel F. Delaney,et al.  Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation , 2011, Science.

[4]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[5]  H Allen Orr THE POPULATION GENETICS OF ADAPTATION ON CORRELATED FITNESS LANDSCAPES: THE BLOCK MODEL , 2006, Evolution; international journal of organic evolution.

[6]  J. Krug,et al.  Clonal interference in large populations , 2007, Proceedings of the National Academy of Sciences.

[7]  Claudia Bank,et al.  SHIFTING FITNESS LANDSCAPES IN RESPONSE TO ALTERED ENVIRONMENTS , 2013, Evolution; international journal of organic evolution.

[8]  Claudia Bank,et al.  A systematic survey of an intragenic epistatic landscape , 2014, bioRxiv.

[9]  A. Perelson,et al.  Protein evolution on partially correlated landscapes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Richard E. Lenski,et al.  Bacterial Population Negative Epistasis Between Beneficial Mutations in an Evolving , 2012 .

[11]  Y Husimi,et al.  A cross-section of the fitness landscape of dihydrofolate reductase. , 2001, Protein engineering.

[12]  M. Ostermeier,et al.  Environmental changes bridge evolutionary valleys , 2016, Science Advances.

[13]  H. Moriyama,et al.  Epistasis Among Adaptive Mutations in Deer Mouse Hemoglobin , 2013, Science.

[14]  Michael M. Desai,et al.  The Speed of Evolution and Maintenance of Variation in Asexual Populations , 2007, Current Biology.

[15]  H. A. Orr,et al.  The population genetics of speciation: the evolution of hybrid incompatibilities. , 1995, Genetics.

[16]  Sergey Kryazhimskiy,et al.  The dynamics of adaptation on correlated fitness landscapes , 2009, Proceedings of the National Academy of Sciences.

[17]  H. A. Orr,et al.  The genetic theory of adaptation: a brief history , 2005, Nature Reviews Genetics.

[18]  Michael M. Desai,et al.  Global epistasis makes adaptation predictable despite sequence-level stochasticity , 2014, Science.

[19]  J. Draghi,et al.  SELECTION BIASES THE PREVALENCE AND TYPE OF EPISTASIS ALONG ADAPTIVE TRAJECTORIES , 2012, Evolution; international journal of organic evolution.

[20]  Craig R. Miller,et al.  The Consistency of Beneficial Fitness Effects of Mutations across Diverse Genetic Backgrounds , 2012, PloS one.

[21]  J. Maynard Smith Natural Selection and the Concept of a Protein Space , 1970 .

[22]  H. A. Orr,et al.  Theories of adaptation: what they do and don’t say , 2005, Genetica.

[23]  Thanat Chookajorn,et al.  Stepwise acquisition of pyrimethamine resistance in the malaria parasite , 2009, Proceedings of the National Academy of Sciences.

[24]  Nigel F. Delaney,et al.  Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins , 2006, Science.

[25]  Robert B. Heckendorn,et al.  Should evolutionary geneticists worry about higher-order epistasis? , 2013, Current opinion in genetics & development.

[26]  S. Kauffman,et al.  Towards a general theory of adaptive walks on rugged landscapes. , 1987, Journal of theoretical biology.

[27]  James B. Anderson,et al.  Incipient speciation by divergent adaptation and antagonistic epistasis in yeast , 2007, Nature.

[28]  P. Joyce,et al.  Properties of adaptive walks on uncorrelated landscapes under strong selection and weak mutation. , 2006, Journal of theoretical biology.

[29]  D. Weinreich,et al.  RAPID EVOLUTIONARY ESCAPE BY LARGE POPULATIONS FROM LOCAL FITNESS PEAKS IS LIKELY IN NATURE , 2005, Evolution; international journal of organic evolution.

[30]  Joachim Krug,et al.  Evolutionary Accessibility of Mutational Pathways , 2011, PLoS Comput. Biol..

[31]  Joachim Krug,et al.  Patterns of Epistasis between Beneficial Mutations in an Antibiotic Resistance Gene , 2013, Molecular biology and evolution.

[32]  Elena R. Lozovsky,et al.  Compensatory mutations restore fitness during the evolution of dihydrofolate reductase. , 2010, Molecular biology and evolution.

[33]  R. Punnett,et al.  The Genetical Theory of Natural Selection , 1930, Nature.

[34]  F. J. Poelwijk,et al.  Environmental Dependence of Genetic Constraint , 2013, PLoS genetics.

[35]  J. Krug,et al.  Empirical fitness landscapes and the predictability of evolution , 2014, Nature Reviews Genetics.

[36]  Dmitry Chudakov,et al.  Local fitness landscape of the green fluorescent protein , 2016, Nature.

[37]  J. Gillespie MOLECULAR EVOLUTION OVER THE MUTATIONAL LANDSCAPE , 1984, Evolution; international journal of organic evolution.

[38]  J. Krug,et al.  Quantitative analyses of empirical fitness landscapes , 2012, 1202.4378.

[39]  Benjamin H. Good,et al.  Distribution of fixed beneficial mutations and the rate of adaptation in asexual populations , 2012, Proceedings of the National Academy of Sciences.

[40]  Thomas Lenormand,et al.  Distributions of epistasis in microbes fit predictions from a fitness landscape model , 2007, Nature Genetics.

[41]  A. Kondrashov,et al.  Multidimensional epistasis and the disadvantage of sex , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Rafael Sanjuán,et al.  The contribution of epistasis to the architecture of fitness in an RNA virus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[44]  Craig R. Miller,et al.  Stickbreaking: A Novel Fitness Landscape Model That Harbors Epistasis and Is Consistent with Commonly Observed Patterns of Adaptive Evolution , 2012, Genetics.

[45]  S. Otto,et al.  The Evolutionary Enigma of Sex , 2009, The American Naturalist.

[46]  D. Mosier,et al.  Fitness Epistasis and Constraints on Adaptation in a Human Immunodeficiency Virus Type 1 Protein Region , 2010, Genetics.

[47]  Craig R. Miller,et al.  Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus , 2011, PLoS genetics.

[48]  Eugene V. Koonin,et al.  Predictability of Evolutionary Trajectories in Fitness Landscapes , 2011, PLoS Comput. Biol..

[49]  Craig R. Miller,et al.  Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models , 2011, Genetics.

[50]  H. Moriyama,et al.  Epistasis Constrains Mutational Pathways of Hemoglobin Adaptation in High-Altitude Pikas , 2014, Molecular biology and evolution.

[51]  Adrian W. R. Serohijos,et al.  Merging molecular mechanism and evolution: theory and computation at the interface of biophysics and evolutionary population genetics. , 2014, Current opinion in structural biology.

[52]  A. Wong,et al.  A Bayesian MCMC Approach to Assess the Complete Distribution of Fitness Effects of New Mutations: Uncovering the Potential for Adaptive Walks in Challenging Environments , 2014, Genetics.

[53]  Craig R. Miller,et al.  Environment Determines Epistatic Patterns for a ssDNA Virus , 2013, Genetics.

[54]  N. Barton Fitness Landscapes and the Origin of Species , 2004 .

[55]  J. Krug,et al.  Exploring the Effect of Sex on Empirical Fitness Landscapes , 2009, The American Naturalist.

[56]  Stephen P. Miller,et al.  The Biochemical Architecture of an Ancient Adaptive Landscape , 2005, Science.

[57]  Jakub Otwinowski,et al.  Inferring fitness landscapes by regression produces biased estimates of epistasis , 2014, Proceedings of the National Academy of Sciences.

[58]  T. Lenormand,et al.  A GENERAL MULTIVARIATE EXTENSION OF FISHER'S GEOMETRICAL MODEL AND THE DISTRIBUTION OF MUTATION FITNESS EFFECTS ACROSS SPECIES , 2006, Evolution; international journal of organic evolution.

[59]  Marcelo Kallmann,et al.  Designing Antibiotic Cycling Strategies by Determining and Understanding Local Adaptive Landscapes , 2013, PloS one.

[60]  François Blanquart,et al.  Epistasis and the Structure of Fitness Landscapes: Are Experimental Fitness Landscapes Compatible with Fisher’s Geometric Model? , 2015, Genetics.

[61]  J. Hailman Wonderful Life: The Burgess Shale and the Nature of History, Stephen Jay Gould. W. W. Norton, New York (1989), 347, Price $19.95 (U.S.A.), $27.95 (Canada) , 1991 .

[62]  G. Fox,et al.  Equally Parsimonious Pathways Through an RNA Sequence Space Are Not Equally Likely , 1997, Journal of Molecular Evolution.

[63]  Elena R. Lozovsky,et al.  Biophysical principles predict fitness landscapes of drug resistance , 2016, Proceedings of the National Academy of Sciences.

[64]  J. Gillespie The causes of molecular evolution , 1991 .