Papers in the Biological Sciences


Natural Genetic Variation in Transcriptome Reflects Network Structure Inferred with Major Effect Mutations: Insulin/TOR and Associated Phenotypes in Drosophila melanogaster

Sergey Nuzhdin, University of Southern California, Los Angeles, CA
Jennifer A. Brisson, University of Nebraska - Lincoln
Andrew Pickering, University of Southern California, Los Angeles, CA
Marta Wayne, University of Florida, Gainesville F
Lawrence G. Harshman, University of Nebraska - Lincoln
Lauren McIntyre, University of Florida, Gainesville F

Published in BMC Genomics 2009, 10:124 doi:10.1186/1471-2164-10-124 This article is available from: Copyright © 2009 Nuzhdin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: A molecular process based genotype-to-phenotype map will ultimately enable us to predict how genetic variation among individuals results in phenotypic alterations. Building such a map is, however, far from straightforward. It requires understanding how molecular variation reshapes developmental and metabolic networks, and how the functional state of these networks modifies phenotypes in genotype specific way. We focus on the latter problem by describing genetic variation in transcript levels of genes in the InR/TOR pathway among 72 Drosophila melanogaster genotypes.
Results: We observe tight co-variance in transcript levels of genes not known to influence each other through direct transcriptional control. We summarize transcriptome variation with factor analyses, and observe strong co-variance of gene expression within the dFOXO-branch and within the TOR-branch of the pathway. Finally, we investigate whether major axes of transcriptome variation shape phenotypes expected to be influenced through the InR/TOR pathway. We find limited evidence that transcript levels of individual upstream genes in the InR/TOR pathway predict fly phenotypes in expected ways. However, there is no evidence that these effects are mediated through the major axes of downstream transcriptome variation.
Conclusion: In summary, our results question the assertion of the 'sparse' nature of genetic networks, while validating and extending candidate gene approaches in the analyses of complex traits.