View Program - 63rd Annual Drosophila Research Conference

DNA in the nucleus is nonrandomly organized into chromosomal territories, compartments, and topological associated domains or TADs. Chromosomal rearrangements have the potential to reorganize this structure, which could potentially lead to altered gene expression. In humans, genome rearrangements can lead to altered phenotypes, genetic diseases, and cancer due to the misregulation of genes. Unlike in humans, paracentric inversions in Drosophila are quite frequent because they do not have the negative effects associated with the formation of unbalanced gametes because males do not recombine, and in females, aberrant meiotic products are lost in polar bodies. As a result, Drosophila populations can harbor extensive gene arrangement variation in populations. However, it is not clear whether natural selection acts to remove genome rearrangements because breakpoints alter gene expression because of changes in chromatin architecture. Liao et al. (2021) found that TAD structure is conserved over long- evolutionary time between D. melanogaster and D. pseudoobscura. We used the recent inversion events within D. pseudoobscura to determine if chromatin architecture (TAD structure) constrains where breakpoints occur over short-evolutionary time. D. pseudoobscura has an abundance of different gene arrangements on the third chromosome. Several hypotheses have been proposed for how new mutations are established in populations including the position effect hypothesis that suggests that inversion breakpoints produce variation for selection to act. We test whether the third chromosome breakpoints alter TAD structure in D. pseudoobscura and whether these disruptions altered gene expression. To determine whether breakpoints are constrained, we used seven pairs of inversion breakpoints in D. pseudoobscura to determine whether they disrupt TADs or fall between adjacent TADs using the TAD maps of Liao et al. (2021). Five of the 13 breakpoints occur at TAD boundaries, which is unlikely due to chance, while eight breakpoints disrupt TADs. We used RNA-Seq data from Fuller et al. (2016) to determine if there are differentially expressed genes in disrupted TADs. Of the eight disrupted TADs, seven had differentially expressed genes. Some breakpoints alter gene expression when TADs are disrupted supporting the hypothesis that position effects may contribute to inversion establishment by generating variation for selection to act.

Chromatin Architecture Constrains Where Inversion Breakpoints Occur Over a Short-Time Scale in D. pseudoobscura