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Pleiotropic scaling of gene effects and the ‘cost of complexity’

Abstract

As perceived by Darwin, evolutionary adaptation by the processes of mutation and selection is difficult to understand for complex features that are the product of numerous traits acting in concert, for example the eye or the apparatus of flight. Typically, mutations simultaneously affect multiple phenotypic characters. This phenomenon is known as pleiotropy. The impact of pleiotropy on evolution has for decades been the subject of formal analysis1,2,3,4,5,6. Some authors have suggested that pleiotropy can impede evolutionary progress (a so-called ‘cost of complexity’5). The plausibility of various phenomena attributed to pleiotropy depends on how many traits are affected by each mutation and on our understanding of the correlation between the number of traits affected by each gene substitution and the size of mutational effects on individual traits. Here we show, by studying pleiotropy in mice with the use of quantitative trait loci (QTLs) affecting skeletal characters, that most QTLs affect a relatively small subset of traits and that a substitution at a QTL has an effect on each trait that increases with the total number of traits affected. This suggests that evolution of higher organisms does not suffer a ‘cost of complexity’ because most mutations affect few traits and the size of the effects does not decrease with pleiotropy.

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Figure 1: Distribution of QTL effects on 70 skeletal traits in the mouse.

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Acknowledgements

We thank A. Pyle, A. Kondrashov and B. Walsh for suggestions that have improved this manuscript. We thank the members of the Wagner and Cheverud laboratories for critical discussion. J.P. and D.W. thank members of the evolution group at Sussex. J.M.C. is funded by the National Institutes of Health and the National Science Foundation (NSF), G.P.W. acknowledges funding from the NSF, the Humboldt Foundation and the John Templeton Foundation, M.P. is funded by the Austrian Science Foundation (FWF) Fellowship, and the work of D.W. was supported by the Leverhulme Trust.

Author Contributions G.P.W. conceived this study, participated in the statistical analysis and wrote the manuscript. J.P.K.-H. collected the morphological data and performed the QTL analysis. M.P. did the statistical analyses. J.M.C. was responsible for generating the mouse populations and the genotype data used in the original mapping and advised on the pleiotropic scaling analysis. J.P. and D.W. performed a theoretical analysis of the scaling of trait effects with pleiotropy. All authors participated in the preparation of the manuscript.

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Correspondence to Günter P. Wagner or James M. Cheverud.

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The file contains Supplementary Figures S1-S4 with Legends, Supplementary Table T1 and Supplementary Notes with additional references. (PDF 356 kb)

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Wagner, G., Kenney-Hunt, J., Pavlicev, M. et al. Pleiotropic scaling of gene effects and the ‘cost of complexity’. Nature 452, 470–472 (2008). https://doi.org/10.1038/nature06756

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