Abstract
Identifying the genetic architecture of complex traits is of interest to many geneticists, including those interested in human disease, plant and animal breeding and evolutionary genetics. Despite advances in sequencing technologies and GWAS statistical methods improving our ability to identify variants with smaller effect sizes, many of these identified polymorphisms fail to be replicated in subsequent studies. In addition to sampling variation, this reflects the complexities introduced by factors including environmental variation, genetic background and differences in allele frequencies among populations. Using Drosophila melanogaster wing shape, we ask if we can replicate allelic effects of polymorphisms first identified in a GWAS (Pitchers et al. 2019) in three genes: dachsous (ds), extra-macrochaete (emc) and neuralized (neur), using artificial selection in the lab and bulk segregant mapping in natural populations. We demonstrate that shape changes associated with these genes is aligned with major axes of phenotypic and genetic variation in natural populations. Following 7 generations of artificial selection along ds and emc shape change vectors, we observe genetic differentiation of variants in ds and in genomic regions with other genes in the hippo signaling pathway, indicating available genetic diversity of a population summarized in G influences alleles captured by selection. Despite the success with artificial selection, bulk segregant analysis using natural populations did not detect these same variants, likely due to the contribution of environmental variation, low minor allele frequencies coupled with small effect sizes of the contributing variants.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵* Co-first authors