Genetic basis of transcriptome diversity in Drosophila melanogaster.
Understanding how DNA sequence variation is translated into variation for complex phenotypes has remained elusive but is essential for predicting adaptive evolution, for selecting agriculturally important animals and crops, and for personalized medicine. Gene expression may provide a link between variation in DNA sequence and organismal phenotypes, and its abundance can be measured efficiently and accurately. Here we quantified genome-wide variation in gene expression in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP), increasing the annotated Drosophila transcriptome by 11%, including thousands of novel transcribed regions (NTRs). We found that 42% of the Drosophila transcriptome is genetically variable in males and females, including the NTRs, and is organized into modules of genetically correlated transcripts. We found that NTRs often were negatively correlated with the expression of protein-coding genes, which we exploited to annotate NTRs functionally. We identified regulatory variants for the mean and variance of gene expression, which have largely independent genetic control. Expression quantitative trait loci (eQTLs) for the mean, but not for the variance, of gene expression were concentrated near genes. Notably, the variance eQTLs often interacted epistatically with local variants in these genes to regulate gene expression. This comprehensive characterization of population-scale diversity of transcriptomes and its genetic basis in the DGRP is critically important for a systems understanding of quantitative trait variation.
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Wen
W
Huang
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Mary Anna
MA
Carbone
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Michael M
MM
Magwire
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Jason A
JA
Peiffer
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Richard F
RF
Lyman
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Eric A
EA
Stone
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695.
Robert R H
RR
Anholt
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695; Program in Genetics, North Carolina State University, Raleigh, NC 27695; W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC 27695 trudy_mackay@ncsu.edu.
Trudy F C
TF
Mackay
D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics*; D004843:Epistasis, Genetic; D040641:Quantitative Trait Loci; D059467:Transcriptome
epistasis; genome-wide association; mean eQTLs; novel transcribed regions; variance eQTLs