In model organism research, both pedigree analyses and genetic crosses in which linkage mapping is used to localize QTL almost always lead to the identification of multiple variants influencing the quantitative trait of interest20. This is as true of threshold-dependent characters and cryptic variation93 as it is of continuous variation. Furthermore, the phenomenon of transgressive segregation in mapping populations of mice and flies established from eight founder strains provides strong empirical support for the existence of common polygenes94–96. The overwhelming evidence from classical quantitative genetics is that traits are regulated by many loci with a wide range of effect sizes. A counterargument is that in any cross or pedigree, there is no information about the frequency of contributing QTL alleles in the population, so some fraction of the mapped factors are likely to be rare variants – and if the parents were selected from a base population, possibly most are unusual rare variants, including mutations that were unconsciously selected in the laboratory. In the past year, re-sequencing of evolved outbred populations of Drosophila melanogaster has provided strong support for selection on thousands of variants being responsible for changes in the highly complex traits of body size and fecundity97,98.
