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Polygenicity and epistasis underlie fitness-proximal traits in the Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel

View ORCID ProfileLuke M. Noble, View ORCID ProfileIvo Chelo, Thiago Guzella, Bruno Afonso, David D. Riccardi, Patrick Ammerman, Adel Dayarian, Sara Carvalho, Anna Crist, Ania Pino-Querido, View ORCID ProfileBoris Shraiman, View ORCID ProfileMatthew V. Rockman, Henrique Teotónio
doi: https://doi.org/10.1101/120865
Luke M. Noble
*Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA,
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Ivo Chelo
†Instituto Gulbenkian de Ciência, Oeiras, Portugal
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Thiago Guzella
§Institut de Biologie, École Normale Supérieure, CNRS UMR 8197, INSERM U1024, F-75005 Paris, France
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Bruno Afonso
§Institut de Biologie, École Normale Supérieure, CNRS UMR 8197, INSERM U1024, F-75005 Paris, France
†Instituto Gulbenkian de Ciência, Oeiras, Portugal
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David D. Riccardi
*Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA,
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Patrick Ammerman
*Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA,
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Adel Dayarian
**Kavli Institute for Theoretical Physics
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Sara Carvalho
†Instituto Gulbenkian de Ciência, Oeiras, Portugal
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Anna Crist
§Institut de Biologie, École Normale Supérieure, CNRS UMR 8197, INSERM U1024, F-75005 Paris, France
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Ania Pino-Querido
†Instituto Gulbenkian de Ciência, Oeiras, Portugal
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Boris Shraiman
**Kavli Institute for Theoretical Physics
‡Department of Physics, University of California, Santa Barbara, CA, 93106, USA
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Matthew V. Rockman
*Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, 10003, USA,
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Henrique Teotónio
§Institut de Biologie, École Normale Supérieure, CNRS UMR 8197, INSERM U1024, F-75005 Paris, France
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ABSTRACT

Understanding the genetic basis of complex traits remains a major challenge in biology. Polygenicity, phenotypic plasticity and epistasis contribute to phenotypic variance in ways that are rarely clear. This uncertainty is problematic for estimating heritability, for predicting individual phenotypes from genomic data, and for parameterizing models of phenotypic evolution. Here we report a recombinant inbred line (RIL) quantitative trait locus (QTL) mapping panel for the hermaphroditic nematode Caenorhabditis elegans, the C. elegans multiparental experimental evolution (CeMEE) panel. The CeMEE panel, comprising 507 RILs, was created by hybridization of 16 wild isolates, experimental evolution at moderate population sizes and predominant outcrossing for 140-190 generations, and inbreeding by selfing for 13-16 generations. The panel contains 22% of single nucleotide polymorphisms known to segregate in natural populations, and complements existing mapping resources for C. elegans by providing high nucleotide diversity across >95% of the genome. We apply it to study the genetic basis of two fitness components, fertility and hermaphrodite body size at time of reproduction, with high broad sense heritability in the CeMEE. While simulations show we should detect common alleles with additive effects as small as 5%, at gene-level resolution, the genetic architectures of these traits does not feature such alleles. We instead find that a significant fraction of trait variance, particularly for fertility, can be explained by sign epistasis with weak main effects. In congruence, phenotype prediction, while generally poor (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the highly recombinant, rapidly evolving chromosome arms.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 27, 2017.
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Polygenicity and epistasis underlie fitness-proximal traits in the Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel
Luke M. Noble, Ivo Chelo, Thiago Guzella, Bruno Afonso, David D. Riccardi, Patrick Ammerman, Adel Dayarian, Sara Carvalho, Anna Crist, Ania Pino-Querido, Boris Shraiman, Matthew V. Rockman, Henrique Teotónio
bioRxiv 120865; doi: https://doi.org/10.1101/120865
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Polygenicity and epistasis underlie fitness-proximal traits in the Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel
Luke M. Noble, Ivo Chelo, Thiago Guzella, Bruno Afonso, David D. Riccardi, Patrick Ammerman, Adel Dayarian, Sara Carvalho, Anna Crist, Ania Pino-Querido, Boris Shraiman, Matthew V. Rockman, Henrique Teotónio
bioRxiv 120865; doi: https://doi.org/10.1101/120865

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