Format

Send to

Choose Destination
Genetics. 2017 Dec;207(4):1663-1685. doi: 10.1534/genetics.117.300406. Epub 2017 Oct 24.

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

Author information

1
Center for Genomics and Systems Biology, Department of Biology, New York University, New York 10003 lmn3@nyu.edu mrockman@nyu.edu teotonio@biologie.ens.fr.
2
Instituto Gulbenkian de Ciência, P-2781-901 Oeiras, Portugal.
3
Institut de Biologie, École Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) UMR 8197, Institut National de la Santé et de la Recherche Médicale (INSERM) U1024, F-75005 Paris, France.
4
Center for Genomics and Systems Biology, Department of Biology, New York University, New York 10003.
5
Kavli Institute for Theoretical Physics, University of California, Santa Barbara, California 93106.
6
Department of Physics, University of California, Santa Barbara, California 93106.
7
Institut de Biologie, École Normale Supérieure, Centre National de la Recherche Scientifique (CNRS) UMR 8197, Institut National de la Santé et de la Recherche Médicale (INSERM) U1024, F-75005 Paris, France lmn3@nyu.edu mrockman@nyu.edu teotonio@biologie.ens.fr.

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 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 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 that we should detect common alleles with additive effects as small as 5%, at gene-level resolution, the genetic architectures of these traits do 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 ([Formula: see text]), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.

KEYWORDS:

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

PMID:
29066469
PMCID:
PMC5714472
DOI:
10.1534/genetics.117.300406
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center