Laboratory evolution of adenylyl cyclase independent learning in Drosophila and missing heritability

Cressy, M., Valente, D., Altick, A., Kockenmesiter, E., Honegger, K., Qin, H., Mitra, P. P., Dubnau, J. (May 2014) Laboratory evolution of adenylyl cyclase independent learning in Drosophila and missing heritability. Genes, Brain and Behavior, 13 (6). pp. 565-577. ISSN 16011848

DOI: 10.1111/gbb.12146


Gene interactions are acknowledged to be a likely source of missing heritability in large-scale genetic studies of complex neurological phenotypes. However, involvement of rare variants, de novo mutations, genetic lesions that are not easily detected with commonly used methods and epigenetic factors also are possible explanations. We used a laboratory evolution study to investigate the modulatory effects of background genetic variation on the phenotypic effect size of a null mutation with known impact on olfactory learning. To accomplish this, we first established a population that contained variation at just 23 loci and used selection to evolve suppression of the learning defect seen with null mutations in the rutabaga adenylyl cyclase. We thus biased the system to favor relatively simplified outcomes by choosing a Mendelian trait and by restricting the genetic variation segregating in the population. This experimental design also assures that the causal effects are among the known 23 segregating loci. We observe a robust response to selection that requires the presence of the 23 variants. Analyses of the underlying genotypes showed that interactions between more than two loci are likely to be involved in explaining the selection response, with implications for the missing heritability problem.

Item Type: Paper
Subjects: organism description > animal > insect > Drosophila
organism description > animal behavior > learning
CSHL Authors:
Communities: CSHL labs > Dubnau lab
CSHL labs > Mitra lab
School of Biological Sciences > Publications
Depositing User: Matt Covey
Date: 31 May 2014
Date Deposited: 13 Jun 2014 15:38
Last Modified: 03 Apr 2015 16:49
PMCID: PMC4108996
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