Abstract
It is now well established that natural populations of Drosophila melanogaster harbor substantial genetic variation associated with physiological measures of immune function. In no case, however, have intermediate measures of immune function, such as transcriptional activity of immune-related genes, been tested as mediators of phenotypic variation in immunity. In this study, we measured bacterial load sustained after infection of D. melanogaster with Serratia marcescens, Providencia rettgeri, Enterococcus faecalis, and Lactococcus lactis in a panel of 94 third-chromosome substitution lines. We also measured transcriptional levels of 329 immune-related genes eight hours after infection with E. faecalis and S. marcescens in lines from the phenotypic tails of the test panel. We genotyped the substitution lines at 137 polymorphic markers distributed across 25 genes in order to test for statistical associations among genotype, bacterial load, and transcriptional dynamics. We find that genetic polymorphisms in the pathogen recognition genes (and particularly in PGRP-LC, GNBP1, and GNBP2) are most significantly associated with variation in bacterial load. We also find that overall transcriptional induction of effector proteins is a significant predictor of bacterial load after infection with E. faecalis, and that a marker upstream of the recognition gene PGRP-SD is statistically associated with variation in both bacterial load and transcriptional induction of effector proteins. These results show that polymorphism in genes near the top of the immune system signaling cascade can have a disproportionate effect on organismal phenotype due to the amplification of minor effects through the cascade.
Highlights
Drosophila, like other insects, use a generalized immune response to combat pathogens
We find that statistical associations between genetic variants and bacterial load tend to cluster in genes encoding proteins involved in microbial recognition
Variation in suppression of bacterial growth is determined in part by genetic variation in the expression of downstream components of the immune system that function to directly kill bacteria, despite finding no genetic variation in any single of these effector gene significantly associated with phenotype
Summary
Drosophila, like other insects, use a generalized immune response to combat pathogens. Despite considerable knowledge of the molecular basis of the Drosophila immune response, and increasing understanding of the extent of natural genetic variation for immunocompetence in this system [2,3,4], relatively little is known about the role of network structure in shaping the phenotypic consequences of genetic variation. Other studies in Drosophila have identified transcriptional variation associated with male reproductive success [6], male body size [7], aggressive behavior [8] and locomotive behavior [9]. While in some cases it has been possible to show that genetically determined transcriptional differences are statistically correlated with phenotypic differences, these studies have generally not identified causal genetic variants
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