{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:35:41Z","timestamp":1791297341941,"version":"4.1.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2012,4,11]],"date-time":"2012-04-11T00:00:00Z","timestamp":1334102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Heredity"],"published-print":{"date-parts":[[2012,8]]},"DOI":"10.1038\/hdy.2012.15","type":"journal-article","created":{"date-parts":[[2012,4,11]],"date-time":"2012-04-11T09:26:17Z","timestamp":1334136377000},"page":"71-77","source":"Crossref","is-referenced-by-count":68,"title":["Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus"],"prefix":"10.1038","volume":"109","author":[{"given":"J","family":"Lali\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S F","family":"Elena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,4,11]]},"reference":[{"key":"BFhdy201215_CR1","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1534\/genetics.104.028696","volume":"168","author":"HC Bagheri","year":"2004","unstructured":"Bagheri HC, Wagner GP (2004). Evolution of dominance in metabolic pathways. Genetics 168: 1716\u20131735.","journal-title":"Genetics"},{"key":"BFhdy201215_CR2","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.virusres.2010.02.004","volume":"149","author":"LC Bedoya","year":"2010","unstructured":"Bedoya LC, Dar\u00f2s JA (2010). Stability of Tobacco etch virus infectious clones in plasmid vectors. Virus Res 149: 234\u2013240.","journal-title":"Virus Res"},{"key":"BFhdy201215_CR3","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/nature05385","volume":"444","author":"S Bershtein","year":"2006","unstructured":"Bershtein S, Segal M, Bekerman R, Tokuriki N, Tawfik DS (2006). Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein. Nature 444: 929\u2013932.","journal-title":"Nature"},{"key":"BFhdy201215_CR4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00239-010-9397-0","volume":"71","author":"AJ Betancourt","year":"2010","unstructured":"Betancourt AJ (2010). Lack of evidence for sign epistasis between beneficial mutations in an RNA bacteriophage. J Mol Evol 71: 437\u2013443.","journal-title":"J Mol Evol"},{"key":"BFhdy201215_CR5","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1126\/science.1101786","volume":"306","author":"S Bonhoeffer","year":"2004","unstructured":"Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ (2004). Evidence for positive epistasis in HIV-1. Science 306: 1547\u20131550.","journal-title":"Science"},{"key":"BFhdy201215_CR6","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1534\/genetics.103.021196","volume":"167","author":"CL Burch","year":"2004","unstructured":"Burch CL, Chao L (2004). Epistasis and its relationship to canalization in the RNA virus \u03c66. Genetics 167: 559\u2013567.","journal-title":"Genetics"},{"key":"BFhdy201215_CR7","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jviromet.2006.09.020","volume":"139","author":"P Carrasco","year":"2007","unstructured":"Carrasco P, Dar\u00f2s JA, Agudelo-Romero P, Elena SF (2007a). A real-time RT-PCR assay for quantifying the fitness of Tobacco etch virus in competition experiments. J Virol Meth 139: 181\u2013188.","journal-title":"J Virol Meth"},{"key":"BFhdy201215_CR8","doi-asserted-by":"publisher","first-page":"12979","DOI":"10.1128\/JVI.00524-07","volume":"81","author":"P Carrasco","year":"2007","unstructured":"Carrasco P, de la Iglesia F, Elena SF (2007b). Distribution of fitness and virulence effects caused by single-nucleotide substitutions in Tobacco etch virus. J Virol 81: 12979\u201312984.","journal-title":"J Virol"},{"key":"BFhdy201215_CR9","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1128\/JVI.02712-06","volume":"81","author":"M Cong","year":"2007","unstructured":"Cong M, Heneine W, Garc\u00eda-Lerma JG (2007). The fitness cost of mutations associated with Human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions. J Virol 81: 3037\u20133041.","journal-title":"J Virol"},{"key":"BFhdy201215_CR10","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/355511a0","volume":"355","author":"JA Coyne","year":"1992","unstructured":"Coyne JA (1992). Genetics and speciation. Nature 355: 511\u2013515.","journal-title":"Nature"},{"key":"BFhdy201215_CR11","volume-title":"An Introduction to Population Genetics Theory","author":"JF Crow","year":"1970","unstructured":"Crow JF, Kimura M (1970) An Introduction to Population Genetics Theory. Harper and Row New York."},{"key":"BFhdy201215_CR12","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1534\/genetics.109.112458","volume":"185","author":"J Da Silva","year":"2010","unstructured":"Da Silva J, Coetzer M, Nedellec R, Pastore C, Mosier DE (2010). Fitness epistasis and constraints on adaptation in a Human immunodeficiency virus type 1 protein region. Genetics 185: 293\u2013303.","journal-title":"Genetics"},{"key":"BFhdy201215_CR13","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1534\/genetics.107.075812","volume":"177","author":"MM Desai","year":"2007","unstructured":"Desai MM, Weissman D, Feldman MW (2007). Evolution can favor antagonistic epistasis. Genetics 177: 1001\u20131010.","journal-title":"Genetics"},{"key":"BFhdy201215_CR14","doi-asserted-by":"publisher","first-page":"4941","DOI":"10.1128\/JVI.02528-06","volume":"81","author":"F De la Iglesia","year":"2007","unstructured":"De la Iglesia F, Elena SF (2007). Fitness declines in Tobacco etch virus upon serial bottleneck transfers. J Virol 81: 4941\u20134947.","journal-title":"J Virol"},{"key":"BFhdy201215_CR15","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nrg1985","volume":"8","author":"JAGM De Visser","year":"2007","unstructured":"De Visser JAGM, Elena SF (2007). The evolution of sex: empirical insights into the roles of epistasis and drift. Nat Rev Genet 8: 139\u2013149.","journal-title":"Nat Rev Genet"},{"key":"BFhdy201215_CR16","first-page":"1959","volume":"57","author":"JAGM De Visser","year":"2003","unstructured":"De Visser JAGM, Hermisson J, Wagner GP, Ancel-Meyers L, Bagheri-Chaichian H, Blanchard JL et al. (2003). Perspective: Evolution and detection of genetic robustness. Evolution 57: 1959\u20131972.","journal-title":"Evolution"},{"key":"BFhdy201215_CR17","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1098\/rspb.2011.1537","volume":"10","author":"JAGM De Visser","year":"2011","unstructured":"De Visser JAGM, Cooper TF, Elena SF (2011). The causes of epistasis. Proc R Soc B 10: 3617\u20133624.","journal-title":"Proc R Soc B"},{"key":"BFhdy201215_CR18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1162\/106454604773563595","volume":"10","author":"JA Edlund","year":"2004","unstructured":"Edlund JA, Adami C (2004). Evolution of robustness in digital organisms. Artif Life 10: 167\u2013179.","journal-title":"Artif Life"},{"key":"BFhdy201215_CR19","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/PL00000082","volume":"49","author":"SF Elena","year":"1999","unstructured":"Elena SF (1999). Little evidence for synergism among deleterious mutations in a nonsegmented RNA virus. J Mol Evol 49: 703\u2013707.","journal-title":"J Mol Evol"},{"key":"BFhdy201215_CR20","doi-asserted-by":"publisher","first-page":"026106","DOI":"10.1063\/1.3449300","volume":"20","author":"SF Elena","year":"2010","unstructured":"Elena SF, Sol\u00e9 RV, Sardany\u00e9s J (2010). Simple genomes, complex interactions: epistasis in RNA virus. Chaos 20: 026106.","journal-title":"Chaos"},{"key":"BFhdy201215_CR21","doi-asserted-by":"publisher","first-page":"e1002134","DOI":"10.1371\/journal.pcbi.1002134","volume":"7","author":"J Franke","year":"2011","unstructured":"Franke J, Kl\u00f6zer A, de Visser JAGM, Krug J (2011). Evolutionary accessibility of mutational pathways. PLoS Comp Biol 7: e1002134.","journal-title":"PLoS Comp Biol"},{"key":"BFhdy201215_CR22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/978-1-60761-175-2_12","volume":"563","author":"S Killcoyne","year":"2009","unstructured":"Killcoyne S, Carter GW, Smith J, Boyle J (2009). Cytoscape: a community-based framework for network modeling. Meth Mol Biol 563: 219\u2013239.","journal-title":"Meth Mol Biol"},{"key":"BFhdy201215_CR23","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1093\/genetics\/136.4.1469","volume":"136","author":"AS Kondrashov","year":"1994","unstructured":"Kondrashov AS (1994). Muller\u2019s ratchet under epistatic selection. Genetics 136: 1469\u20131473.","journal-title":"Genetics"},{"key":"BFhdy201215_CR24","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/351314a0","volume":"351","author":"AS Kondrashov","year":"1991","unstructured":"Kondrashov AS, Crow JF (1991). Haploidy or diploidy: which is better. Nature 351: 314\u2013315.","journal-title":"Nature"},{"key":"BFhdy201215_CR25","doi-asserted-by":"publisher","first-page":"12089","DOI":"10.1073\/pnas.211214298","volume":"98","author":"FA Kondrashov","year":"2001","unstructured":"Kondrashov FA, Kondrashov AS (2001). Multidimensional epistasis and the disadvantage of sex. Proc Natl Acad Sci USA 98: 12089\u201312092.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFhdy201215_CR26","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.tree.2007.02.014","volume":"6","author":"RD Kouyos","year":"2007","unstructured":"Kouyos RD, Silander OK, Bonhoeffer S (2007). Epistasis between deleterious mutations and the evolution of recombination. Trends Ecol Evol 6: 308\u2013315.","journal-title":"Trends Ecol Evol"},{"key":"BFhdy201215_CR27","doi-asserted-by":"publisher","first-page":"e1002056","DOI":"10.1371\/journal.pgen.1002056","volume":"7","author":"DJ Kvitek","year":"2011","unstructured":"Kvitek DJ, Sherlock G (2011). Reciprocal sign epistasis between frequently experimentally evolved adaptive mutations causes a rugged fitness landscape. PLoS Genet 7: e1002056.","journal-title":"PLoS Genet"},{"key":"BFhdy201215_CR28","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1111\/j.1558-5646.2011.01451.x","volume":"66","author":"J Mac\u00eda","year":"2012","unstructured":"Mac\u00eda J, Sol\u00e9 RV, Elena SF (2012). The causes of epistasis in genetic networks. Evolution 66: 586\u2013596.","journal-title":"Evolution"},{"key":"BFhdy201215_CR29","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1046\/j.1365-2958.2002.03173.x","volume":"46","author":"S Maisnier-Patin","year":"2002","unstructured":"Maisnier-Patin S, Berg OG, Lijas L, Andersson DI (2002). Compensatory adaptation to the deleterious effect of antibiotic resistance in Salmonella typhimurium. Mol Microbiol 46: 355\u2013366.","journal-title":"Mol Microbiol"},{"key":"BFhdy201215_CR30","doi-asserted-by":"publisher","first-page":"e18375","DOI":"10.1371\/journal.pone.0018375","volume":"6","author":"JP Mart\u00ednez","year":"2011","unstructured":"Mart\u00ednez JP, Bocharov G, Ignatovich A, Reiter J, Dittmar MT, Wain-Hobson S et al. (2011). Fitness ranking of individual mutants drives patterns of epistatic interactions in HIV-1. PLoS ONE 6: e18375.","journal-title":"PLoS ONE"},{"key":"BFhdy201215_CR31","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.virusres.2007.12.021","volume":"134","author":"J Mart\u00ednez-Picado","year":"2009","unstructured":"Mart\u00ednez-Picado J, Mart\u00ednez MA (2009). HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: a view from the clinic and ex vivo. Virus Res 134: 104\u2013123.","journal-title":"Virus Res"},{"key":"BFhdy201215_CR32","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1038\/nm0796-760","volume":"2","author":"A Molla","year":"1996","unstructured":"Molla A, Korneyeve M, Gao Q, Vasavanonda S, Schipper PJ, Mo HM et al. (1996). Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 2: 760\u2013766.","journal-title":"Nat Med"},{"key":"BFhdy201215_CR33","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.jmb.2009.07.015","volume":"392","author":"M Parera","year":"2009","unstructured":"Parera M, P\u00e9rez-\u00c1lvarez N, Clotet B, Mart\u00ednez MA (2009). Epistasis among deleterious mutations in the HIV-1 protease. J Mol Biol 392: 243\u2013250.","journal-title":"J Mol Biol"},{"key":"BFhdy201215_CR34","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1111\/j.1558-5646.2007.00143.x","volume":"67","author":"KM Pepin","year":"2007","unstructured":"Pepin KM, Wichman HA (2007). Variable epistatic effects between mutations at host recognition sites in \u03c6X174. Evolution 67: 1710\u20131724.","journal-title":"Evolution"},{"key":"BFhdy201215_CR35","first-page":"87","volume-title":"A-Z of Quantitative PCR, International University Line","author":"MV Pfaffl","year":"2004","unstructured":"Pfaffl MV (2004). Quantification strategies in real-time PCR. In Bustin SA ed A-Z of Quantitative PCR, International University Line. La Jolla USA. pp 87\u2013112."},{"key":"BFhdy201215_CR36","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/nrg2452","volume":"9","author":"PC Phillips","year":"2008","unstructured":"Phillips PC (2008). Epistasis \u2013 the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet 9: 855\u2013867.","journal-title":"Nat Rev Genet"},{"key":"BFhdy201215_CR37","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nature05451","volume":"445","author":"FJ Poelwijk","year":"2007","unstructured":"Poelwijk FJ, Kiviet DJ, Weinreich DM, Tans SJ (2007). Empirical fitness landscapes reveal accessible evolutionary paths. Nature 445: 383\u2013386.","journal-title":"Nature"},{"key":"BFhdy201215_CR38","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jtbi.2010.12.015","volume":"272","author":"FJ Poelwijk","year":"2011","unstructured":"Poelwijk FJ, Tanase-Nicola S, Kiviet DJ, Tans SJ (2011). Reciprocal sign epistasis is a necessary condition for multi-peaked fitness landscapes. J Theor Biol 272: 141\u2013144.","journal-title":"J Theor Biol"},{"key":"BFhdy201215_CR39","first-page":"2032","volume":"60","author":"AFY Poon","year":"2006","unstructured":"Poon AFY, Chao L (2006). Functional origins of fitness effect-sizes of compensatory mutations in the DNA bacteriophage \u03c6X174. Evolution 60: 2032\u20132043.","journal-title":"Evolution"},{"key":"BFhdy201215_CR40","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1086\/426873","volume":"165","author":"SR Proulx","year":"2005","unstructured":"Proulx SR, Phillips PC (2005). The opportunity for canalization and the evolution of genetic networks. Am Nat 165: 147\u2013162.","journal-title":"Am Nat"},{"key":"BFhdy201215_CR41","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/ng1324","volume":"36","author":"SK Remold","year":"2004","unstructured":"Remold SK, Lenski RE (2004). Pervasive joint influence of epistasis and plasticity on mutational effects in Escherichia coli. Nat Genet 36: 423 426.","journal-title":"Nat Genet"},{"key":"BFhdy201215_CR42","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/j.1558-5646.1989.tb04220.x","volume":"43","author":"WR Rice","year":"1989","unstructured":"Rice WR (1989). Analyzing tables of statistical tests. Evolution 43: 223\u2013225.","journal-title":"Evolution"},{"key":"BFhdy201215_CR43","unstructured":"Rodrigo G, Carrera J, Ruiz-Ferrer V, Del Toro FJ, Llave C, Voinnet O et al. (2011). Characterization of the Arabidopsis thaliana interactome targeted by viruses. Santa Fe Institute Working Paper 11-10-049."},{"key":"BFhdy201215_CR44","doi-asserted-by":"publisher","first-page":"e1002075","DOI":"10.1371\/journal.pgen.1002075","volume":"7","author":"DR Rokyta","year":"2011","unstructured":"Rokyta DR, Joyce P, Caudle B, Miller C, Beisel CJ, Wichman HA (2011). Epistasis between beneficial mutations and the phenotype-to-fitness map for a ssDNA virus. PLoS Genet 7: e1002075.","journal-title":"PLoS Genet"},{"key":"BFhdy201215_CR45","doi-asserted-by":"publisher","first-page":"e1001321","DOI":"10.1371\/journal.pgen.1001321","volume":"7","author":"MLM Salverda","year":"2011","unstructured":"Salverda MLM, Dellus E, Gorter FA, Debets AJM, Van der Oost J, Hoekstra RF et al. (2011). Initial mutations direct alternative pathways of protein evolution. PLoS Genet 7: e1001321.","journal-title":"PLoS Genet"},{"key":"BFhdy201215_CR46","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1099\/vir.0.81585-0","volume":"87","author":"R Sanju\u00e1n","year":"2006","unstructured":"Sanju\u00e1n R (2006). Quantifying antagonistic epistasis in a multifunctional RNA secondary structure of the Rous sarcoma virus. J Gen Virol 87: 1595\u20131602.","journal-title":"J Gen Virol"},{"key":"BFhdy201215_CR47","doi-asserted-by":"publisher","first-page":"14402","DOI":"10.1073\/pnas.0604543103","volume":"103","author":"R Sanju\u00e1n","year":"2006","unstructured":"Sanju\u00e1n R, Elena SF (2006). Epistasis correlates to genomic complexity. Proc Natl Acad Sci USA 103: 14402\u201314405.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFhdy201215_CR48","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1093\/molbev\/msl083","volume":"23","author":"R Sanju\u00e1n","year":"2006","unstructured":"Sanju\u00e1n R, Forment J, Elena SF (2006). In silico predicted robustness of viroids RNA secondary structure. II. Interaction between mutation pairs. Mol Biol Evol 23: 2123\u20132130.","journal-title":"Mol Biol Evol"},{"key":"BFhdy201215_CR49","doi-asserted-by":"publisher","first-page":"15376","DOI":"10.1073\/pnas.0404125101","volume":"101","author":"R Sanju\u00e1n","year":"2004","unstructured":"Sanju\u00e1n R, Moya A, Elena SF (2004). The contribution of epistasis to the architecture of fitness in an RNA virus. Proc Natl Acad Sci USA 101: 15376\u201315379.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFhdy201215_CR50","doi-asserted-by":"publisher","first-page":"e2663","DOI":"10.1371\/journal.pone.0002663","volume":"3","author":"R Sanju\u00e1n","year":"2008","unstructured":"Sanju\u00e1n R, Nebot MR (2008). A network model for the correlation between epistasis and genomic complexity. PLoS ONE 3: e2663.","journal-title":"PLoS ONE"},{"key":"BFhdy201215_CR51","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1098\/rspb.1997.0178","volume":"264","author":"SJ Schrag","year":"1997","unstructured":"Schrag SJ, Perrot V, Levin BR (1997). Adaptation to the fitness cost of antibiotic resistance in E. coli. Proc R Soc B 264: 1287\u20131291.","journal-title":"Proc R Soc B"},{"key":"BFhdy201215_CR52","doi-asserted-by":"publisher","first-page":"6678","DOI":"10.1128\/JVI.02547-05","volume":"80","author":"T Van Opijnen","year":"2006","unstructured":"Van Opijnen T, Boerlijst MC, Berkhout B (2006). Effects of random mutations in the Human immunodeficiency virus type 1 transcriptional promoter on viral fitness in different host cell environments. J Virol 80: 6678\u20136685.","journal-title":"J Virol"},{"key":"BFhdy201215_CR53","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1534\/genetics.104.036830","volume":"171","author":"DM Weinreich","year":"2005","unstructured":"Weinreich DM (2005). The rank ordering of genotypic fitness values predicts genetic constraints on natural selection on landscapes lacking sign epistasis. Genetics 171: 1397\u20131405.","journal-title":"Genetics"},{"key":"BFhdy201215_CR54","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1126\/science.1123539","volume":"312","author":"DM Weinreich","year":"2006","unstructured":"Weinreich DM, Delaney NF, DePristo MA, Hartl DL (2006). Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312: 111\u2013114.","journal-title":"Science"},{"key":"BFhdy201215_CR55","first-page":"1165","volume":"59","author":"DM Weinreich","year":"2005","unstructured":"Weinreich DM, Watson RA, Chao L (2005). Perspective: sign epistasis and genetic constraint on evolutionary trajectories. Evolution 59: 1165\u20131174.","journal-title":"Evolution"},{"key":"BFhdy201215_CR56","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.jtbi.2004.11.027","volume":"234","author":"JJ Welch","year":"2005","unstructured":"Welch JJ, Waxman D (2005). The nk model and population genetics. J Theor Biol 234: 329\u2013340.","journal-title":"J Theor Biol"},{"key":"BFhdy201215_CR57","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1098\/rspb.2001.1690","volume":"298","author":"CO Wilke","year":"2001","unstructured":"Wilke CO, Adami C (2001). Interaction between directional epistasis and average mutational effects. Proc R Soc B 298: 1469\u20131474.","journal-title":"Proc R Soc B"},{"key":"BFhdy201215_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2148-3-3","volume":"3","author":"CO Wilke","year":"2003","unstructured":"Wilke CO, Lenski RE, Adami C (2003). Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding. BMC Evol Biol 3: 1\u201314.","journal-title":"BMC Evol Biol"},{"key":"BFhdy201215_CR59","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1146\/annurev.es.26.110195.003125","volume":"26","author":"MC Withlock","year":"1995","unstructured":"Withlock MC, Phillips PC, Moore FBG, Tonsor SJ (1995). Multiple fitness peaks and epistasis. Annu Rev Ecol Evol Syst 26: 601\u2013629.","journal-title":"Annu Rev Ecol Evol Syst"},{"key":"BFhdy201215_CR60","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/genetics\/160.4.1273","volume":"160","author":"L You","year":"2002","unstructured":"You L, Yin J (2002). Dependence of epistasis on environment and mutation severity as revealed by in silico mutagenesis of phage T7. Genetics 160: 1273\u20131281.","journal-title":"Genetics"}],"container-title":["Heredity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/hdy201215.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/hdy201215","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/hdy201215.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:44:45Z","timestamp":1684431885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/hdy201215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,11]]},"references-count":60,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["BFhdy201215"],"URL":"https:\/\/doi.org\/10.1038\/hdy.2012.15","relation":{},"ISSN":["0018-067X","1365-2540"],"issn-type":[{"value":"0018-067X","type":"print"},{"value":"1365-2540","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,11]]}}}