Powerful decomposition of complex traits in a diploid model.
Explaining trait differences between individuals is a core and challenging aim of life sciences. Here, we introduce a powerful framework for complete decomposition of trait variation into its underlying genetic causes in diploid model organisms. We sequence and systematically pair the recombinant gametes of two intercrossed natural genomes into an array of diploid hybrids with fully assembled and phased genomes, termed Phased Outbred Lines (POLs). We demonstrate the capacity of this approach by partitioning fitness traits of 6,642 Saccharomyces cerevisiae POLs across many environments, achieving near complete trait heritability and precisely estimating additive (73%), dominance (10%), second (7%) and third (1.7%) order epistasis components. We map quantitative trait loci (QTLs) and find nonadditive QTLs to outnumber (3:1) additive loci, dominant contributions to heterosis to outnumber overdominant, and extensive pleiotropy. The POL framework offers the most complete decomposition of diploid traits to date and can be adapted to most model organisms.
Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, 06107 Nice, France.
Johan
J
Hallin
Institute of Computer Science, University of Tartu, 50090 Tartu, Estonia.
Kaspar
K
Märtens
Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, UK.
Alexander I
AI
Young
Department of Chemistry and Molecular Biology, Gothenburg University, 405 30 Gothenburg, Sweden.
Martin
M
Zackrisson
Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, 06107 Nice, France.
Francisco
0000-0002-8391-8145
F
Salinas
Institute of Computer Science, University of Tartu, 50090 Tartu, Estonia.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA Hinxton, UK.
Leopold
L
Parts
Department of Chemistry and Molecular Biology, Gothenburg University, 405 30 Gothenburg, Sweden.|Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, 1430 Ås, Norway.
Jonas
0000-0001-6144-2740
J
Warringer
Institute for Research on Cancer and Aging, Nice (IRCAN), CNRS UMR7284, INSERM U1081, University of Nice Sophia Antipolis, 06107 Nice, France.
Gianni
G
Liti
D002874:Chromosome Mapping; D004171:Diploidy; D006823:Hybrid Vigor / Q000235:genetics; D006824:Hybridization, Genetic; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D012441:Saccharomyces cerevisiae / Q000235:genetics*