TY - JOUR
T1 - Polygenicity and epistasis underlie fitness-proximal traits in the Caenorhabditis elegans multiparental experimental evolution (CeMEE) panel
AU - Noble, Luke M.
AU - Chelo, Ivo
AU - Guzella, Thiago
AU - Afonso, Bruno
AU - Riccardi, David D.
AU - Ammerman, Patrick
AU - Dayarian, Adel
AU - Carvalho, Sara
AU - Crist, Anna
AU - Pino-Querido, Ania
AU - Shraiman, Boris
AU - Rockman, Matthew V.
AU - Teotónio, Henrique
N1 - Publisher Copyright:
© 2017 by the Genetics Society of America.
PY - 2017/12
Y1 - 2017/12
N2 - 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 (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.
AB - 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 (r2 < 10%), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.
KW - Body size
KW - Complex trait
KW - Epistasis
KW - Experimental evolution
KW - Fertility
KW - GWAS
KW - Genetic architecture
KW - Heritability
KW - MPP
KW - Multiparent advanced Generation Inter-Cross (MAGIC)
KW - Multiparental populations
KW - Polygenicity
KW - QTL
KW - Quantitative trait
KW - Selfing
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U2 - 10.1534/genetics.117.300406
DO - 10.1534/genetics.117.300406
M3 - Article
C2 - 29066469
AN - SCOPUS:85037053965
SN - 0016-6731
VL - 207
SP - 1663
EP - 1685
JO - Genetics
JF - Genetics
IS - 4
ER -