Consistent blind protein structure generation from NMR chemical shift data

Abstract
In higher organisms, the phenotypic impacts of potentially harmful or beneficial mutations are often modulated by complex developmental networks. Stabilizing selection may favor the evolution of developmental canalization—that is, robustness despite perturbation—to insulate development against environmental and genetic variability. In contrast, directional selection acts to alter the developmental process, possibly undermining the molecular mechanisms that buffer a trait’s development, but this scenario has not been shown in nature. Here, we examined the developmental consequences of size increase in highland Ethiopian Drosophila melanogaster. Ethiopian inbred strains exhibited much higher frequencies of wing abnormalities than lowland populations, consistent with an elevated susceptibility to the genetic perturbation of inbreeding. We then used mutagenesis to test whether Ethiopian wing development is, indeed, decanalized. Ethiopian strains were far more susceptible to this genetic disruption of development, yielding 26 times more novel wing abnormalities than lowland strains in F2 males. Wing size and developmental perturbability cosegregated in the offspring of between-population crosses, suggesting that genes conferring size differences had undermined developmental buffering mechanisms. Our findings represent the first observation, to our knowledge, of morphological evolution associated with decanalization in the same tissue, underscoring the sensitivity of development to adaptive change. Significance Developmental buffering mechanisms that stabilize phenotypes against perturbations (such as harmful mutations or environmental stress) have previously been inferred. However, it is unclear whether this “canalization” can be maintained when adaptive evolution causes phenotypes and developmental processes to change. Here, we report a loss of canalization accompanying the evolution of larger wings in high-altitude fruit flies (Drosophila melanogaster). We redeploy a classic genetics technique (mutagenesis) to show that wing development of Ethiopian flies is less robust to new mutations and that large wing size is inherited together with decanalized wing development. These results represent the first example, to our knowledge, of adaptive evolution apparently undermining the developmental buffering of a recently evolved trait. Decanalized development, thus, represents a potential “cost of adaptation.”