Abstract
Genetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome in segregating populations.
The recent explosion of high-throughput data—measuring thousands of proteins and metabolites, deep sequencing, chromatin, and methyl-DNA immunoprecipitation—allows the study of the genetic variation underlying quantitative phenotypes, together termed xQTL. At the same time, mining information is not getting easier. To deal with the sheer amount of information, powerful statistical tools are needed to analyze multidimensional relationships. In the context of evolutionary computational biology, a well-designed experiment may help dissect a complex evolutionary trait using proven statistical methods for associating phenotypical variation with genomic locations.
Evolutionary expression QTL (eQTL) studies of the last years focus on gene expression adaptations, mapping the gene expression landscape, and, tentatively, eQTL networks. Here, we discuss the possibility of introducing an evolutionary prior, in the form of gene families displaying evidence of positive selection, and using that in the context of an eQTL experiment for elucidating host–pathogen protein–protein interactions. Through the example of an experimental design, we discuss the choice of xQTL platform, analysis methods, and scope of results. The resulting eQTL can be matched, resulting in putative interacting genes and their regulators. In addition, a prior may help distinguish QTL causality from reactivity, or independence of traits, by creating QTL networks.
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References
Nandi S, Subudhi P K, Senadhira D et al. (1997) Mapping QTLs for submergence tolerance in rice by AFLP analysis and selective genotyping. Mol Gen Genet. 255:1–8
Meaburn E, Butcher L M, Schalkwyk L C & Plomin R (2006) Genotyping pooled DNA using 100K SNP microarrays: a step towards genomewide association scans. Nucleic Acids Res. 34:e27p
Kim S, Plagnol V, Hu T T et al. (2007) Recombination and linkage disequilibrium in Arabidopsis thaliana. Nat Genet. 39:1151–1155. http://www.ncbi.nlm.nih.gov/pubmed/17676040
Dixon A L, Liang L, Moffatt M F et al. (2007) A genome-wide association study of global gene expression. Nat Genet. 39:1202–1207
Jansen R C & Nap J P (2001) Genetical genomics: the added value from segregation. Trends Genet. 17:388–391
Gibson G & Weir B (2005) The quantitative genetics of transcription. Trends Genet. 21:616–623
Li Y, Alvarez O A, Gutteling E W et al. (2006) Mapping determinants of gene expression plasticity by genetical genomics in C. elegans. PLoS Genet. 2:e222p
Jansen R C, Tesson B M, Fu J, Yang Y & Mcintyre L M (2009) Defining gene and QTL networks. Curr Opin Plant Biol. 12:241–246
Brem R B & Kruglyak L (2005) The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proc Natl Acad Sci USA. 102:1572–1577
Fraser H B, Moses A M & Schadt E E (2010) Evidence for widespread adaptive evolution of gene expression in budding yeast. Proc Natl Acad Sci U S A. 107:2977–2982
Zou Y, Su Z, Yang J, Zeng Y & Gu X (2009) Uncovering genetic regulatory network divergence between duplicate genes using yeast eqtl landscape. J Exp Zool B Mol Dev Evol. 312:722–733
Li Y, Breitling R & Jansen R C (2008) Generalizing genetical genomics: getting added value from environmental perturbation. Trends Genet. 24:518–524. http://www.ncbi.nlm.nih.gov/pubmed/18774198
Kliebenstein D J, West M A, van Leeuwen H et al. (2006) Identification of QTLs controlling gene expression networks defined a priori. BMC Bioinformatics. 7:308p
Gilad Y, Rifkin S A & Pritchard J K (2008) Revealing the architecture of gene regulation: the promise of eQTL studies. Trends Genet. 24:408–415
Alberts R, Terpstra P, Li Y et al. (2007) Sequence polymorphisms cause many false cis eqtls. PLoS One. 2:e622p
Franke L, Bakel H v, Fokkens L et al. (2006) Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes. Am J Hum Genet. 78:1011–1025
Chen X, Hackett C A, Niks R E et al. (2010) An eqtl analysis of partial resistance to puccinia hordei in barley. PLoS One. 5:e8598p
Qin L, Kudla U, Roze E H et al. (2004) Plant degradation: a nematode expansin acting on plants. Nature. 427:30p. doi:10.1038/427030a
Saijo Y & Schulze-lefert P (2008) Manipulation of the eukaryotic transcriptional machinery by bacterial pathogens. Cell Host Microbe. 4:96–99
Chen L Q, Hou B H, Lalonde S et al. (2010) Sugar transporters for intercellular exchange and nutrition of pathogens. Nature. 468:527–532
Hewitson J P, Grainger J R & Maizels R M (2009) Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol Biochem Parasitol. 167:1–11
Bird P I, Trapani J A & Villadangos J A (2009) Endolysosomal proteases and their inhibitors in immunity. Nat Rev Immunol. 9:871–882. doi:10.1038/nri2671
Bevan M, Bancroft I, Bent E et al. (1998) Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana. Nature. 391:485–488. doi:10.1038/35140
Bishop J G, Dean A M & Mitchell-olds T (2000) Rapid evolution in plant chitinases: molecular targets of selection in plant–pathogen coevolution. Proc Natl Acad Sci USA. 97:5322–5327
Dangl J L & Jones J D (2001) Plant pathogens and integrated defence responses to infection. Nature. 411:826–833. doi:10.1038/35081161
Flor H (1956) The complementary genic systems in flax and flax rust*. Advances in Genetics. 8:29–54. doi:10.1016/S0065-2660(08)60498-8
Bakker E G, Toomajian C, Kreitman M & Bergelson J (2006) A genome-wide survey of R gene polymorphisms in Arabidopsis. Plant Cell. 18:1803–1818. doi:10.1105/tpc.106.042614
Mackey D, Belkhadir Y, Alonso J M, Ecker J R & Dangl J L (2003) Arabidopsis rin4 is a target of the type iii virulence effector avrrpt2 and modulates rps2-mediated resistance. Cell. 112:379–389
Richly E, Kurth J & Leister D (2002) Mode of amplification and reorganization of resistance genes during recent arabidopsis thaliana evolution. Mol Biol Evol. 19:76–84
Medzhitov R & Janeway C A J (1997) Innate immunity: impact on the adaptive immune response. Curr Opin Immunol. 9:4–9
Holub E B (2001) The arms race is ancient history in Arabidopsis, the wildflower. Nat Rev Genet. 2:516–527. doi:10.1038/35080508
Xiao S, Emerson B, Ratanasut K et al. (2004) Origin and maintenance of a broad-spectrum disease resistance locus in Arabidopsis. Mol Biol Evol. 21:1661–1672. doi:10.1093/molbev/msh165
Mondragon-Palomino M, Meyers B C, Michelmore R W & Gaut B S (2002) Patterns of positive selection in the complete NBS-LRR gene family of Arabidopsis thaliana. Genome Res. 12:1305–1315. doi:10.1101/gr.159402
Sun X, Cao Y & Wang S (2006) Point mutations with positive selection were a major force during the evolution of a receptor-kinase resistance gene family of rice. Plant Physiol. 140:998–1008. doi:10.1104/pp.105.073080
Yang Z (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci. 13:555–556. http://www.ncbi.nlm.nih.gov/pubmed/9367129
Kosiol, C., & Anisimova, M. (2012) Selection on the protein coding genome. In: Anisimova, M., (ed.), Evolutionary genomics: statistical and computational methods (volume 1). Methods in Molecular Biology, Springer Science+Business Media New York
Prins, P., Belhachemi, D., Möller, S. & Smant, G. (2012) Scalable computing in evolutionary genomics. In: Anisimova, M., (ed.), Evolutionary genomics: statistical and computational methods (volume 1). Methods in Molecular Biology, Springer Science+Business Media New York
Altschul S F, Madden T L, Schaffer A A et al. (1997) Gapped blast and psi-blast: a new generation of protein database search programs. Nucleic Acids Res. 25:3389–3402
Edgar R C (2004) Muscle: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32:1792–1797. doi:10.1093/nar/gkh340
Suyama M, Torrents D & Bork P (2006) Pal2nal: robust conversion of protein sequence alignments into the corresponding codon alignments. Nucleic Acids Res. 34:W609-W612. doi:10.1093/nar/gkl315
Goto N, Prins P, Nakao M et al. (2010) BioRuby: bioinformatics software for the Ruby programming language. Bioinformatics. 26:2617–2619. doi:10.1093/bioinformatics/btq475
Altschul S F, Madden T L, Schaffer A A et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25:3389–3402
Rhee S Y, Beavis W, Berardini T Z et al. (2003) The Arabidopsis Information Resource (TAIR): a model organism database providing a centralized, curated gateway to Arabidopsis biology, research materials and community. Nucleic Acids Res. 31:224–228. http://www.ncbi.nlm.nih.gov/pubmed/12519987
Anisimova M, Nielsen R & Yang Z (2003) Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. Genetics. 164:1229–1236
(2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature. 408:796–815
Michelmore R W & Meyers B C (1998) Clusters of resistance genes in plants evolve by divergent selection and a birth-and-death process. Genome Res. 8:1113–1130. http://www.ncbi.nlm.nih.gov/pubmed/9847076
Salinas J & Sanchez-serrano J (2006) Arabidopsis protocols. Humana Pr Inc, Totowa, NJ
Fu J & Jansen R C (2006) Optimal design and analysis of genetic studies on gene expression. Genetics. 172:1993–1999. doi:10.1534/genetics.105.047001
Mortazavi A, Williams B A, Mccue K, Schaeffer L & Wold B (2008) Mapping and quantifying mammalian transcriptomes by rna-seq. Nat Methods. 5:621–628. doi:10.1038/nmeth.1226
Eklund A C, Turner L R, Chen P et al. (2006) Replacing cRNA targets with cDNA reduces microarray cross-hybridization. Nat Biotechnol. 24:1071–1073. doi:10.1038/nbt0906-1071
Hoen P A, Ariyurek Y, Thygesen H H et al. (2008) Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms. Nucleic Acids Res. 36:e141p. doi:10.1093/nar/gkn705
Keurentjes J J, Sulpice R, Gibon Y et al. (2008) Integrative analyses of genetic variation in enzyme activities of primary carbohydrate metabolism reveal distinct modes of regulation in Arabidopsis thaliana. Genome Biol. 9:R129p. doi:10.1186/gb-2008-9-8-r129
Fu J, Swertz M A, Keurentjes J J & Jansen R C (2007) Metanetwork: a computational protocol for the genetic study of metabolic networks. Nat Protoc. 2:685–694. doi:10.1038/nprot.2007.96
Fu J, Keurentjes J J, Bouwmeester H et al. (2009) System-wide molecular evidence for phenotypic buffering in Arabidopsis. Nat Genet. 41:166–167. doi:10.1038/ng.308
Breitling R, Li Y, Tesson B M et al. (2008) Genetical genomics: spotlight on QTL hotspots. PLoS Genet. 4:e1000232p. doi:10.1371/journal.pgen.1000232
Development core team R (2010) R: a language and environment for statistical computing. http://www.R-project.org
Broman K & Sen (2009) A guide to QTL mapping with R/qtl. Springer Verlag, New York, NY
Arends D, Prins P, Jansen R C & Broman K W (2010) R/qtl: high-throughput multiple QTL mapping. Bioinformatics. 26:2990–2992. doi:10.1093/bioinformatics/btq565
Tierney L, Rossini A & Li N (2009) SNOW: a parallel computing framework for the R system. International Journal of Parallel Programming. 37:78–90
Arends D, Prins P, Broman K W & Jansen R C (2010) Tutorial – Multiple-QTL Mapping (MQM) Analysis. http://www.rqtl.org/tutorials/MQM-tour.pdf
Li Y, Tesson B M, Churchill G A & Jansen R C (2010) Critical reasoning on causal inference in genome-wide linkage and association studies. Trends Genet. 26:493–498. doi:10.1016/j.tig.2010.09.002
Wayne M L & Mcintyre L M (2002) Combining mapping and arraying: an approach to candidate gene identification. Proc Natl Acad Sci USA. 99:14903–14906. doi:10.1073/pnas.222549199
Westra HJ, Jansen RC, Fehrmann RS, te Meerman GJ, van Heel D, Wijmenga C, Franke L. (2011) MixupMapper: correcting sample mix-ups in genome-wide datasets increases power to detect small genetic effects. Bioinformatics. Aug 1;27(15):2104–11. Epub 2011 Jun 7. http://www.ncbi.nlm.nih.gov/pubmed/21653519
Acknowledgments
The European Commission’s Integrated Project BIOEXPLOIT (FOOD-2005-513959 to GS and PP); the Netherlands Organization for Scientific Research/TTI Green Genetics (1CC029RP to PP); the EU 7th Framework Programme under the Research Project PANACEA (222936 to RJ).
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Prins, P., Smant, G., Jansen, R.C. (2012). Genetical Genomics for Evolutionary Studies. In: Anisimova, M. (eds) Evolutionary Genomics. Methods in Molecular Biology, vol 856. Humana Press. https://doi.org/10.1007/978-1-61779-585-5_19
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