Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information

Abstract

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

Figure 1

Genetic architecture of startle response controlled directly by highly significant 22 QTSs and 29 QTTs, and indirectly by 39 tQTTs and 14 tQTSs. The red nodes represent QTSs and green nodes are transcripts. The label above the node denotes the gene name. A “Y” shape line between two nodes denotes the epistasis effect. Red and green lines denote positive effects, while black and blue lines denote negative effects. Yellow lines denote positive effect in female and negative effect in male, and orange lines denote positive effect in male and negative effect in female. The width of lines denotes the value of estimate with a wider line representing a higher estimate.