Population-Based Resequencing of Experimentally Evolved Populations Reveals the Genetic Basis of Body Size Variation in Drosophila melanogaster

Body size is a classic quantitative trait with evolutionarily significant variation within many species. Locating the alleles responsible for this variation would help understand the maintenance of variation in body size in particular, as well as quantitative traits in general. However, successful genome-wide association of genotype and phenotype may require very large sample sizes if alleles have low population frequencies or modest effects. As a complementary approach, we propose that population-based resequencing of experimentally evolved populations allows for considerable power to map functional variation. Here, we use this technique to investigate the genetic basis of natural variation in body size in Drosophila melanogaster. Significant differentiation of hundreds of loci in replicate selection populations supports the hypothesis that the genetic basis of body size variation is very polygenic in D. melanogaster. Significantly differentiated variants are limited to single genes at some loci, allowing precise hypotheses to be formed regarding causal polymorphisms, while other significant regions are large and contain many genes. By using significantly associated polymorphisms as a priori candidates in follow-up studies, these data are expected to provide considerable power to determine the genetic basis of natural variation in body size.

[1]  F. W. Robertson The ecological genetics of growth in Drosophila 6. The genetic correlation between the duration of the larval period and body size in relation to larval diet. , 1963 .

[2]  Brad T. Sherman,et al.  DAVID: Database for Annotation, Visualization, and Integrated Discovery , 2003, Genome Biology.

[3]  V. French,et al.  Correlated responses to selection on body size in Drosophila melanogaster. , 1999, Genetical research.

[4]  J. Wall,et al.  Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster. , 2003, Genetics.

[5]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[6]  J. Bull,et al.  Experimental evolution recapitulates natural evolution. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[7]  T. Day,et al.  An Evolutionary Cost of Separate Genders Revealed by Male‐Limited Evolution , 2006, The American Naturalist.

[8]  Mats E. Pettersson,et al.  Genome-Wide Effects of Long-Term Divergent Selection , 2010, PLoS genetics.

[9]  K. Harvey,et al.  Lgl, aPKC, and Crumbs Regulate the Salvador/Warts/Hippo Pathway through Two Distinct Mechanisms , 2010, Current Biology.

[10]  Annalise B. Paaby,et al.  Identification of a candidate adaptive polymorphism for Drosophila life history by parallel independent clines on two continents , 2010, Molecular ecology.

[11]  A. Hoffmann,et al.  A clinally varying promoter polymorphism associated with adaptive variation in wing size in Drosophila , 2010, Molecular ecology.

[12]  W. Rice,et al.  A Cost of Sexual Attractiveness to High-Fitness Females , 2009, PLoS biology.

[13]  Z. Bochdanovits,et al.  Latitudinal clines inDrosophila melanogaster: Body size, allozyme frequencies, inversion frequencies, and the insulin-signalling pathway , 2003, Journal of Genetics.

[14]  R. Kohler, Lords of the fly: Drosophila genetics and the experimental life. , 1995 .

[15]  S. Nuzhdin,et al.  Genome-enabled hitchhiking mapping identifies QTLs for stress resistance in natural Drosophila , 2007, Heredity.

[16]  R. Lande,et al.  Viable Populations for Conservation: Effective population size, genetic variation, and their use in population management , 1987 .

[17]  Juan Huang,et al.  Crumbs Regulates Salvador/Warts/Hippo Signaling in Drosophila via the FERM-Domain Protein Expanded , 2010, Current Biology.

[18]  Nilanjan Chatterjee,et al.  Estimation of effect size distribution from genome-wide association studies and implications for future discoveries , 2010, Nature Genetics.

[19]  L. Partridge,et al.  DIRECT AND CORRELATED RESPONSES TO SELECTION ON AGE AT REPRODUCTION IN DROSOPHILA MELANOGASTER , 1992, Evolution; international journal of organic evolution.

[20]  H. Handa,et al.  Drosophila FACT contributes to Hox gene expression through physical and functional interactions with GAGA factor. , 2003, Genes & development.

[21]  L. Riddiford,et al.  Size assessment and growth control: how adult size is determined in insects , 2007, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  M. Nordborg,et al.  Conditions Under Which Genome-Wide Association Studies Will be Positively Misleading , 2010, Genetics.

[23]  Kevin R. Thornton,et al.  Genome-wide analysis of a long-term evolution experiment with Drosophila , 2010, Nature.

[24]  Ayellet V. Segrè,et al.  Hundreds of variants clustered in genomic loci and biological pathways affect human height , 2010, Nature.

[25]  S. Pitnick,et al.  Harm to females increases with male body size in Drosophila melanogaster , 2002, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[26]  V. French,et al.  EVOLUTION AND DEVELOPMENT OF BODY SIZE AND CELL SIZE IN DROSOPHILA MELANOGASTER IN RESPONSE TO TEMPERATURE , 1994, Evolution; international journal of organic evolution.

[27]  Bjarni J. Vilhjálmsson,et al.  Genome-wide association study of 107 phenotypes in Arabidopsis thaliana inbred lines , 2010 .

[28]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[29]  F. W. Robertson,et al.  Studies in quantitative inheritance , 1952, Journal of Genetics.

[30]  J. Bundgaard,et al.  The influence of male and female body size on copulation duration and fecundity in Drosophila melanogaster. , 2004, Hereditas.

[31]  Karl Johan Åström,et al.  Autonomous Control , 1992, 25th Anniversary of INRIA.

[32]  P. Capy,et al.  Phenotypic and genetic variability of morphometrical traits in natural populations of Drosophila melanogaster and D simulans. I. Geographic variations , 1993, Genetics Selection Evolution.

[33]  V. Loeschcke,et al.  Consequences of outbreeding on phenotypic plasticity in Drosophila mercatorum wings , 2009, Evolutionary Ecology.

[34]  Neil Hall,et al.  Antagonistic coevolution accelerates molecular evolution , 2010, Nature.

[35]  I. Hariharan Growth Regulation: A Beginning for the Hippo Pathway , 2006, Current Biology.

[36]  D. Goldstein,et al.  Nonclinality of molecular variation implicates selection in maintaining a morphological cline of Drosophila melanogaster. , 2001, Genetics.

[37]  W. Rice,et al.  Inter-locus antagonistic coevolution as an engine of speciation: Assessment with hemiclonal analysis , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[38]  E. Hafen,et al.  Autonomous Control of Cell and Organ Size by CHICO, a Drosophila Homolog of Vertebrate IRS1–4 , 1999, Cell.

[39]  M. Soulé,et al.  Viable Populations for Conservation , 1987 .

[40]  D. Hogness,et al.  The L63 gene is necessary for the ecdysone-induced 63E late puff and encodes CDK proteins required for Drosophila development. , 2000, Developmental biology.

[41]  R. Garofalo,et al.  The Drosophila insulin receptor is required for normal growth. , 1996, Endocrinology.

[42]  K. Morikawa,et al.  Phosphorylated Intrinsically Disordered Region of FACT Masks Its Nucleosomal DNA Binding Elements* , 2009, The Journal of Biological Chemistry.

[43]  David Osumi-Sutherland,et al.  FlyBase: enhancing Drosophila Gene Ontology annotations , 2008, Nucleic Acids Res..

[44]  L. Partridge,et al.  Lifetime mating success of male fruitflies (Drosophila melanogaster) is related to their size , 1983, Animal Behaviour.

[45]  Jeffrey E. Barrick,et al.  Genome evolution and adaptation in a long-term experiment with Escherichia coli , 2009, Nature.

[46]  W. Rice,et al.  Negative genetic correlation for adult fitness between sexes reveals ontogenetic conflict in Drosophila. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[47]  P. Visscher,et al.  Common SNPs explain a large proportion of heritability for human height , 2011 .

[48]  J. M. Smith,et al.  The hitch-hiking effect of a favourable gene. , 1974, Genetical research.

[49]  M. A. Russell The ecological genetics of growth in Drosophila , 1969 .

[50]  V. Loeschcke,et al.  TEMPERATURE‐INDUCED SHIFTS IN ASSOCIATIONS OF LONGEVITY WITH BODY SIZE IN DROSOPHILA MELANOGASTER , 2002, Evolution; international journal of organic evolution.

[51]  L. Gilbert,et al.  Developmental arrest and ecdysteroid deficiency resulting from mutations at the dre4 locus of Drosophila. , 1992, Genetics.