composite effects of polymorphisms near multiple regulatory elements create a major-effect qtl复合多态性的影响附近多个监管元素创建一个主要影响qtl.pdfVIP

Composite Effects of Polymorphisms near Multiple Regulatory Elements Create a Major-Effect QTL 1,2 3 2 Ryan D. Bickel *, Artyom Kopp , Sergey V. Nuzhdin 1 School of Biological Science, University of Nebraska – Lincoln, Lincoln, Nebraska, United States of America, 2 Program in Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America, 3 Department of Evolution and Ecology, University of California Davis, Davis, California, United States of America Abstract Many agriculturally, evolutionarily, and medically important characters vary in a quantitative fashion. Unfortunately, the genes and sequence variants accounting for this variation remain largely unknown due to a variety of biological and technical challenges. Drosophila melanogaster contains high levels of sequence variation and low linkage disequilibrium, allowing us to dissect the effects of many causative variants within a single locus. Here, we take advantage of these features to identify and characterize the sequence polymorphisms that comprise major effect QTL alleles segregating at the bric-a- brac locus. We show that natural bric-a-brac alleles with large effects on cuticular pigmentation reflect a cumulative impact of polymorphisms that affect three functional regions: a promoter, a tissue-specific enhancer, and a Polycomb response element. Analysis of allele-specific expression at the bric-a-brac locus confirms that these polymorphisms modulate transcription at the cis-regulatory level. Our results establish that a single QTL can act through a confluence of multiple molecular mechanisms and that sequence variation in regions flanking experimentally valida