Pelletier, K. | bioRxiv Science

bioRxiv2022

Complexities of recapitulating polygenic effects in natural populations: replication of genetic effects on wing shape in artificially selected and wild caught populations of Drosophila melanogaster.

Identifying the genetic architecture of complex traits is important to many geneticists, including those interested in human disease, plant and animal breeding, and evolutionary genetics. Advances in sequencing technology and statistical methods for genome-wide association studies (GWAS) have allowed for the identification of more variants with smaller effect sizes, however, many of these identified polymorphisms fail to be replicated in subsequent studies. In addition to sampling variation, this failure to replicate 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 multivariate wing shape changes associated with these genes are aligned with major axes of phenotypic and genetic variation in natural populations. Following seven generations of artificial selection along the ds shape change vector, we observe genetic differentiation of variants in ds and genomic regions containing other genes in the hippo signaling pathway. This suggests a shared direction of effects within a developmental network. We also performed artificial selection with the emc shape change vector, which is not a part of the hippo signaling network, but showed a largely shared direction of effects. The response to selection along the emc vector was similar to that of ds, suggesting that the available genetic diversity of a population, summarized by the genetic (co)variance matrix (G), influenced 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 and low minor allele frequencies, coupled with small effect sizes of the contributing variants.

genetics↗

bioRxiv2022

Reexamining Waddington: Canalization and new mutations are not required for the evolution of genetic assimilation

Over 65 years ago, Waddington demonstrated ancestrally phenotypically plastic traits can evolve to become constitutive, a process he termed genetic assimilation. Genetic assimilation evolves rapidly, assumed to be in large part due to segregating genetic variation only expressed in rare/novel environments, but otherwise phenotypically cryptic. Despite previous work suggesting a substantial role of cryptic genetic variation contributing to the evolution of genetic assimilation, some have argued for a prominent role for new mutations of large effect concurrent with selection. Interestingly, Waddington was less concerned by the relative contribution of CGV or new variants, but aimed to test the role of canalization, an evolved form of robustness. While canalization has been extensively studied, its role in the evolution of genetic assimilation is disputed, in part because explicit tests of evolved robustness are lacking. To address these questions, we recreated Waddingtons selection experiments on an environmentally sensitive change in Drosophila wing morphology (crossvein development), using many independently evolved replicate lineages. Using these, we show that 1) a polygenic CGV, but not new variants of large effect are largely responsible for the evolved response demonstrated using both genomic and genetic approaches. 2) Using both environmental manipulations and mutagenesis of the evolved lineages that there is no evidence for evolved changes in canalization contributing to genetic assimilation. Finally, we demonstrate that 3) CGV has potentially pleiotropic and fitness consequences in natural populations and may not be entirely "cryptic".

evolutionary biology↗