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A mutation accumulation assay reveals a broad capacity for rapid evolution of gene expression

Abstract

Mutation is the ultimate source of biological diversity because it generates the variation that fuels evolution1. Gene expression is the first step by which an organism translates genetic information into developmental change. Here we estimate the rate at which mutation produces new variation in gene expression by measuring transcript abundances across the genome during the onset of metamorphosis in 12 initially identical Drosophila melanogaster lines that independently accumulated mutations for 200 generations2. We find statistically significant mutational variation for 39% of the genome and a wide range of variability across corresponding genes. As genes are upregulated in development their variability decreases, and as they are downregulated it increases, indicating that developmental context affects the evolution of gene expression. A strong correlation between mutational variance and environmental variance shows that there is the potential for widespread canalization3. By comparing the evolutionary rates that we report here with differences between species4,5, we conclude that gene expression does not evolve according to strictly neutral models. Although spontaneous mutations have the potential to generate abundant variation in gene expression, natural variation is relatively constrained.

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Figure 1: Mutational heritability.
Figure 2: Mutational variance and differences between species.
Figure 3: Opportunity for canalization.
Figure 4: Developmental context of mutational heritability.

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Acknowledgements

We thank G. Wagner, S. Rice, J. Powell, M. Lynch, J. Fry, G. Gibson, P. Gibbs, T.-R. Li, J. D. Lambert and members of the Kim and White laboratories for suggestions, help and comments. This work was supported by a National Library of Medicine fellowship (to S.A.R.), an NIH grant (to J.K.), and grants from the W.M. Keck Foundation, the Arnold and Mabel Beckman Foundation, and the NIH and National Human Genome Research Institute (to K.P.W.). Author Contributions S.A.R. and J.K. planned and designed the project in consultation with D.H. and K.P.W. Expression data was collected by S.A.R. using spotted microarrays developed by K.P.W. D.H. generated and maintained the mutation accumulation lines. S.A.R. and J.K. developed the computational analyses and carried out the quantitative genetics modelling. S.A.R. wrote the paper with contributions from all authors.

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Correspondence to Junhyong Kim or Kevin P. White.

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Microarray data have been deposited in the Gene Expression Omnibus under accession numbers GSE2126 (mutation accumulation lines), GSE2641 (technical error) and GSE2642 (comparative data update and extension). Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Data 1

Estimates from the genome-wide mixed model analyses of the full and jackknifed datasets. (TXT 4289 kb)

Supplementary Data 2

SAS PROC MIXED calls for the model hierarchy. (DOC 35 kb)

Supplementary Methods

Additional details of the methods used in this study. (PDF 57 kb)

Supplementary Figure 1

Schematic of sample collection. (DOC 393 kb)

Supplementary Figure 2

Mutational heritability versus expression level. (DOC 72 kb)

Supplementary Figure 3

Experimental design. (DOC 192 kb)

Supplementary Figure 4

Likelihood ratio tests order along the model hierarchy. (DOC 220 kb)

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Rifkin, S., Houle, D., Kim, J. et al. A mutation accumulation assay reveals a broad capacity for rapid evolution of gene expression. Nature 438, 220–223 (2005). https://doi.org/10.1038/nature04114

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