The power to detect quantitative trait loci using resequenced, experimentally evolved populations of diploid, sexual organisms

Mol Biol Evol. 2014 Apr;31(4):1040-55. doi: 10.1093/molbev/msu048. Epub 2014 Jan 18.

Abstract

A novel approach for dissecting complex traits is to experimentally evolve laboratory populations under a controlled environment shift, resequence the resulting populations, and identify single nucleotide polymorphisms (SNPs) and/or genomic regions highly diverged in allele frequency. To better understand the power and localization ability of such an evolve and resequence (E&R) approach, we carried out forward-in-time population genetics simulations of 1 Mb genomic regions under a large combination of experimental conditions, then attempted to detect significantly diverged SNPs. Our analysis indicates that the ability to detect differentiation between populations is primarily affected by selection coefficient, population size, number of replicate populations, and number of founding haplotypes. We estimate that E&R studies can detect and localize causative sites with 80% success or greater when the number of founder haplotypes is over 500, experimental populations are replicated at least 25-fold, population size is at least 1,000 diploid individuals, and the selection coefficient on the locus of interest is at least 0.1. More achievable experimental designs (less replicated, fewer founder haplotypes, smaller effective population size, and smaller selection coefficients) can have power of greater than 50% to identify a handful of SNPs of which one is likely causative. Similarly, in cases where s ≥ 0.2, less demanding experimental designs can yield high power.

Keywords: QTL detection; adaptive evolution; evolve and resequence; experimental evolution; genomics; simulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Computer Simulation
  • Diploidy
  • Drosophila melanogaster / genetics
  • Evolution, Molecular
  • Gene Frequency
  • Genes, Insect
  • Genetic Drift
  • Genetic Markers
  • Lod Score
  • Models, Genetic*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Sequence Analysis, DNA

Substances

  • Genetic Markers