Genetic Complexity and Quantitative Trait Loci Mapping of Yeast Morphological Traits

Overview

Journal PLoS Genet

Specialty Genetics

Date 2007 Feb 27

PMID 17319748

Citations 53

Authors

Satoru Nogami

Yoshikazu Ohya

Gael Yvert

Affiliations

Soon will be listed here.

Abstract

Functional genomics relies on two essential parameters: the sensitivity of phenotypic measures and the power to detect genomic perturbations that cause phenotypic variations. In model organisms, two types of perturbations are widely used. Artificial mutations can be introduced in virtually any gene and allow the systematic analysis of gene function via mutants fitness. Alternatively, natural genetic variations can be associated to particular phenotypes via genetic mapping. However, the access to genome manipulation and breeding provided by model organisms is sometimes counterbalanced by phenotyping limitations. Here we investigated the natural genetic diversity of Saccharomyces cerevisiae cellular morphology using a very sensitive high-throughput imaging platform. We quantified 501 morphological parameters in over 50,000 yeast cells from a cross between two wild-type divergent backgrounds. Extensive morphological differences were found between these backgrounds. The genetic architecture of the traits was complex, with evidence of both epistasis and transgressive segregation. We mapped quantitative trait loci (QTL) for 67 traits and discovered 364 correlations between traits segregation and inheritance of gene expression levels. We validated one QTL by the replacement of a single base in the genome. This study illustrates the natural diversity and complexity of cellular traits among natural yeast strains and provides an ideal framework for a genetical genomics dissection of multiple traits. Our results did not overlap with results previously obtained from systematic deletion strains, showing that both approaches are necessary for the functional exploration of genomes.

Citing Articles

Unraveling the genetics of arsenic toxicity with cellular morphology QTL.

OConnor C, Keele G, Martin W, Stodola T, Gatti D, Hoffman B PLoS Genet. 2024; 20(4):e1011248.

PMID: 38662777 PMC: 11075906. DOI: 10.1371/journal.pgen.1011248.

Cell morphology QTL reveal gene by environment interactions in a genetically diverse cell population.

OConnor C, Keele G, Martin W, Stodola T, Gatti D, Hoffman B bioRxiv. 2023; .

PMID: 38014303 PMC: 10680806. DOI: 10.1101/2023.11.18.567597.

The impact of genomic variation on protein phosphorylation states and regulatory networks.

Grossbach J, Gillet L, Clement-Ziza M, Schmalohr C, Schubert O, Schutter M Mol Syst Biol. 2022; 18(5):e10712.

PMID: 35574625 PMC: 9109056. DOI: 10.15252/msb.202110712.

Optimizing bulk segregant analysis of drug resistance using genetic crosses conducted in humanized mice.

Brenneman K, Li X, Kumar S, Delgado E, Checkley L, Shoue D iScience. 2022; 25(4):104095.

PMID: 35372813 PMC: 8971943. DOI: 10.1016/j.isci.2022.104095.

Decoupling gene functions from knockout effects by evolutionary analyses.

Liu L, Liu M, Zhang D, Deng S, Chen P, Yang J Natl Sci Rev. 2021; 7(7):1169-1180.

PMID: 34692141 PMC: 8288921. DOI: 10.1093/nsr/nwaa079.

References

Schadt E, Lamb J, Yang X, Zhu J, Edwards S, GuhaThakurta D . An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet. 2005; 37(7):710-7. PMC: 2841396. DOI: 10.1038/ng1589. View

Deutschbauer A, Davis R . Quantitative trait loci mapped to single-nucleotide resolution in yeast. Nat Genet. 2005; 37(12):1333-40. DOI: 10.1038/ng1674. View

Simon V, Karmon S, Pon L . Mitochondrial inheritance: cell cycle and actin cable dependence of polarized mitochondrial movements in Saccharomyces cerevisiae. Cell Motil Cytoskeleton. 1997; 37(3):199-210. DOI: 10.1002/(SICI)1097-0169(1997)37:3<199::AID-CM2>3.0.CO;2-2. View

Tabor H, Risch N, Myers R . Candidate-gene approaches for studying complex genetic traits: practical considerations. Nat Rev Genet. 2002; 3(5):391-7. DOI: 10.1038/nrg796. View

Valdar W, Solberg L, Gauguier D, Burnett S, Klenerman P, Cookson W . Genome-wide genetic association of complex traits in heterogeneous stock mice. Nat Genet. 2006; 38(8):879-87. DOI: 10.1038/ng1840. View

Carlborg O, de Koning D, Manly K, Chesler E, Williams R, Haley C . Methodological aspects of the genetic dissection of gene expression. Bioinformatics. 2004; 21(10):2383-93. DOI: 10.1093/bioinformatics/bti241. View

Auwerx J, Avner P, Baldock R, Ballabio A, Balling R, Barbacid M . The European dimension for the mouse genome mutagenesis program. Nat Genet. 2004; 36(9):925-7. PMC: 2716028. DOI: 10.1038/ng0904-925. View

Winzeler E, Richards D, Conway A, Goldstein A, Kalman S, McCullough M . Direct allelic variation scanning of the yeast genome. Science. 1998; 281(5380):1194-7. DOI: 10.1126/science.281.5380.1194. View

Ohya Y, Sese J, Yukawa M, Sano F, Nakatani Y, Saito T . High-dimensional and large-scale phenotyping of yeast mutants. Proc Natl Acad Sci U S A. 2005; 102(52):19015-20. PMC: 1316885. DOI: 10.1073/pnas.0509436102. View

10.

Yvert G, Brem R, Whittle J, Akey J, Foss E, Smith E . Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors. Nat Genet. 2003; 35(1):57-64. DOI: 10.1038/ng1222. View

11.

Schadt E, Monks S, Drake T, Lusis A, Che N, Colinayo V . Genetics of gene expression surveyed in maize, mouse and man. Nature. 2003; 422(6929):297-302. DOI: 10.1038/nature01434. View

12.

Halme A, Bumgarner S, Styles C, Fink G . Genetic and epigenetic regulation of the FLO gene family generates cell-surface variation in yeast. Cell. 2004; 116(3):405-15. DOI: 10.1016/s0092-8674(04)00118-7. View

13.

Brem R, Kruglyak L . The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proc Natl Acad Sci U S A. 2005; 102(5):1572-7. PMC: 547855. DOI: 10.1073/pnas.0408709102. View

14.

Brem R, Yvert G, Clinton R, Kruglyak L . Genetic dissection of transcriptional regulation in budding yeast. Science. 2002; 296(5568):752-5. DOI: 10.1126/science.1069516. View

15.

Homann O, Cai H, Becker J, Lindquist S . Harnessing natural diversity to probe metabolic pathways. PLoS Genet. 2006; 1(6):e80. PMC: 1342634. DOI: 10.1371/journal.pgen.0010080. View

16.

Fay J, Benavides J . Evidence for domesticated and wild populations of Saccharomyces cerevisiae. PLoS Genet. 2005; 1(1):66-71. PMC: 1183524. DOI: 10.1371/journal.pgen.0010005. View

17.

Mackay T . The genetic architecture of quantitative traits: lessons from Drosophila. Curr Opin Genet Dev. 2004; 14(3):253-7. DOI: 10.1016/j.gde.2004.04.003. View

18.

Churchill G, Airey D, Allayee H, Angel J, Attie A, Beatty J . The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 2004; 36(11):1133-7. DOI: 10.1038/ng1104-1133. View

19.

Pruyne D, BRETSCHER A . Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. J Cell Sci. 2000; 113 ( Pt 3):365-75. DOI: 10.1242/jcs.113.3.365. View

20.

Perlstein E, Ruderfer D, Ramachandran G, Haggarty S, Kruglyak L, Schreiber S . Revealing complex traits with small molecules and naturally recombinant yeast strains. Chem Biol. 2006; 13(3):319-27. DOI: 10.1016/j.chembiol.2006.01.010. View