Polygenicity and Epistasis Underlie Fitness-Proximal Traits in the Caenorhabditis elegans Multiparental Experimental Evolution (CeMEE) Panel

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 can be problematic for estimating heritability, for predicting individual phenotypes from genomic data, and for parameterizing models of phenotypic evolution. Here we report an advanced 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 at present, was created by hybridization of 16 wild isolates, experimental evolution 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 C. elegans mapping resources by providing fine resolution and 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, approaching 40% for fertility, can be explained by sign epistasis with main effects below the detection limit. In congruence, phenotype prediction from genomic similarity, while generally poor (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.

Description

The deposited article is a pre-print version and it has not been submitted to peer reviewing. This article version was provided by bioRxiv and is the preprint first posted online Mar. 26, 2017. This publication hasn't any creative commons license associated. The deposited article version contains attached the supplementary materials within the pdf.

Keywords

genetic architecture polygenicity epistasis experimental evolution body size fertility selfing GWAS heritability quantitative trait complex trait QTL MPP multiparental populations Multiparent Advanced Generation Inter-Cross (MAGIC)

URI

http://hdl.handle.net/10400.7/815

Citation

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 and Henrique Teotónio Genetics December 1, 2017 vol. 207 no. 4 1663-1685; https://doi.org/10.1534/genetics.117.300406