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Analysis of the leaf metabolome in Arabidopsis thaliana mutation accumulation lines reveals association of metabolic disruption and fitness consequence

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Abstract

Understanding the mechanisms by which mutations affect fitness and the distribution of mutational effects are central goals in evolutionary biology. Mutation accumulation (MA) lines have long been an important tool for understanding the effect of new mutations on fitness, phenotypic variation, and mutational parameters. However, there is a clear gap in predicting the effect of specific new mutations to their effects on fitness. In an attempt to directly connect the effect of spontaneous mutations to their fitness effects, we quantified the metabolic expression of 386 known compounds in primary and secondary metabolism in Arabidopsis thaliana MA lines that had consistently higher and lower relative fitness than the progenitor. The high and low fitness lines do not have a difference in the average number of mutations and share the same types of metabolic pathways disrupted. However, compared to the progenitor, low fitness lines have significantly more metabolic subpathways disrupted than lines with higher fitness. These results suggest that the effect of a new mutation on fitness depends less on the specific metabolic pathways disrupted and potentially more on the number of disrupted pathways. We fail to identify any direct connection of mutations in or near well annotated genes to their effect on well-characterized biochemical pathways, possibly due to incomplete annotations of molecular function or to non-genetic variation controlling metabolic expression. Our findings indicate that organisms can explore a considerable amount of physiological space with only a few mutations.

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Data Availability

All data used in this study (including raw metabolic measures) is represented in the supplementary tables. The datasets will also be uploaded to the Dryad repository upon acceptance.

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Acknowledgements

We thank Detlef Weigel for thoughtful comments and for the generation of the sequencing data. This work was supported by the National Science Foundation (DEB 2017485 to C.F.O.-M, OIA EPSCoR 1920954, DEB 1257902 to C.B.F., DEB 0844820 to C.B.F., DEB 1258053 to M.T.R., and DEB 0845413 to M.T.R.); and the National Institute of Health (INBRE 2P20GM103443-19). A previous version of this paper was available on BioR**v (Kreutzmann, Sydney, Elizabeth Pompa, Nhan Nguyen, Liya Tilahun, Matthew T. Rutter, Mao-Lun Weng, Charles B. Fenster, and Carrie F. Olson-Manning. 2021. “Pleiotropy Is Associated with Fitness Consequences of New Mutations in Mutation Accumulation Lines.” bioRxiv. https://doi.org/10.1101/2021.06.28.450192.)

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Authors and Affiliations

  1. Department of Biology, Augustana University, Sioux Falls, SD, 57105, USA

    Sydney Kreutzmann & Carrie F. Olson-Manning

  2. Department of Chemistry and Biochemistry, Augustana University, Sioux Falls, SD, 57105, USA

    Elizabeth Pompa & Nhan D. Nguyen

  3. Make School, Dominican University of California, San Francisco, CA, 94102, USA

    Liya Tilahun

  4. Department of Biology, College of Charleston, Charleston, SC, 29424, USA

    Matthew T. Rutter

  5. Department of Biology, Westfield State University, Westfield, MA, 01086, USA

    Mao-Lun Weng

  6. South Dakota State University, Oak Lake Field Station, Brookings, SD, 57007, USA

    Charles B. Fenster

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Contributions

All authors contributed to the writing, discussion, and revisions of this manuscript. Author C.F.O.-M., M-L.W. and C.B.F. contributed to experimental design and took part in every contribution listed below. Authors S.K., E.P, N.D.N., and L.T. contributed to data collection and analysis. Author M.T.R. contributed to data analysis.

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Correspondence to Carrie F. Olson-Manning.

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Kreutzmann, S., Pompa, E., Nguyen, N.D. et al. Analysis of the leaf metabolome in Arabidopsis thaliana mutation accumulation lines reveals association of metabolic disruption and fitness consequence. Evol Ecol 36, 845–857 (2022). https://doi.org/10.1007/s10682-022-10210-8

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