Genetic Changes to a Transcriptional Silencer Element Confers Phenotypic Diversity within and between Drosophila Species

Winslow C. Johnson , Alison J. Ordway , Masayoshi Watada, Jonathan N. Pruitt, Thomas M. Williams, Mark Rebeiz

Author Summary

One of the greatest challenges in understanding the relationship between genotype and phenotype is to discern how changes in DNA affect the normal functioning of genes. Mutations may generate a new function for a gene, yet it is frequently observed that they inactivate some aspect of a gene’s normal capacity. Investigations focused on understanding the developmental basis for the evolution of anatomical structures has found a prevalent role for mutations that alter developmental gene regulation. In animals, genes are transcriptionally activated in specific tissues during development by regulatory sequences distributed across their expansive non-protein coding regions. Regulatory elements known as silencers act to prevent genes from being expressed in certain tissues, providing a mechanism for precise control. Here, we show how a silencer that prevents expression of a pigment-producing enzyme in certain Drosophila species has repeatedly been subject to inactivating mutations that increased this gene’s expression. This example illustrates how such negative-acting regulatory sequences can represent a convenient target for increasing gene expression through the loss of a genetic element.

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005279