Position Effect Variegation In Natural Populations Not Explained By Common Variation In Known Modifiers

Abstract

Changes in chromatin state may drive changes in gene expression, and it is of growing interest to understand the population genetic forces that drive differences in chromatin state. Here, we use the phenomenon of position effect variegation (PEV), a well-studied proxy for chromatin state, to explore the genetic architecture of natural variation in factors that modify chromatin state. While previous mutation screens have identified over 150 suppressors and enhancers of PEV, it remains unknown to what extent allelic variation in these modifiers mediates inter-individual variation in chromatin state. Is natural variation in PEV mediated by segregating variation in known Su(var) and E(var) genes, or is the trait polygenic, with many variants mapping elsewhere in the genome? We designed a mapping study that directly answers this question and suggests that the bulk of the variance in PEV does not map to genes with prior annotated impact to PEV. Instead, we find enrichment of top P-value ranked associations that suggest impact to active promoter and transcription start site proximal regions. This work provides a quantitative view of the role naturally segregating autosomal variants play in modifying PEV, a phenomenon that continues to shape our understanding of chromatin state and epigenetics.