Composite Effects of Polymorphisms near Multiple Regulatory Elements Create a Major-Effect QTL

Composite Effects of Polymorphisms near Multiple Regulatory Elements Create a Major-Effect QTL: "Author Summary

Genes responsible for quantitative variation have been identified for a diverse range of phenotypes. However, much remains to be learned about the distribution of causative genetic variation within a locus. In this study, we investigated a locus that contributes to natural variation in abdominal pigmentation in Drosophila melanogaster. We found that the large phenotypic effect of this locus results from the cumulative action of many small-effect polymorphisms that are concentrated in three distinct functional regions: a promoter, a tissue-specific enhancer, and a Polycomb response element (a region involved in chromatin remodeling). The same regions influence the adult phenotype and transcript abundance, indicating that the causative sequence variants act by modulating transcription. Interestingly, these polymorphisms cluster near, but not within, the functionally validated regulatory regions, suggesting that DNA sequences surrounding core functional elements may play a key role in quantitative variation.

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