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Modularity and interactions in the genetics of gene expression.

ABSTRACT: Understanding the effect of genetic sequence variation on phenotype is a major challenge that lies at the heart of genetics. We developed GOLPH (GenOmic Linkage to PHenotype), a statistical method to identify genetic interactions, and used it to characterize the landscape of genetic interactions between gene expression quantitative trait loci. Our results reveal that allele-specific interactions, in which a gene only exerts an influence on the phenotype in the presence of a particular allele at the primary locus, are widespread and that genetic interactions are predominantly nonadditive. The data portray a complex picture in which interacting loci influence the expression of modules of coexpressed genes involved in coherent biological processes and pathways. We show that genetic variation at a single gene can have a major impact on the global transcriptional response, altering interactions between genes through shutdown or activation of pathways. Thus, different cellular states occur not only in response to the external environment but also result from intrinsic genetic variation.

SUBMITTER: Litvin O

PROVIDER: S-EPMC2672504 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Modularity and interactions in the genetics of gene expression.

Litvin Oren O Causton Helen C HC Chen Bo-Juen BJ Pe'er Dana D

Proceedings of the National Academy of Sciences of the United States of America 20090217 16

Understanding the effect of genetic sequence variation on phenotype is a major challenge that lies at the heart of genetics. We developed GOLPH (GenOmic Linkage to PHenotype), a statistical method to identify genetic interactions, and used it to characterize the landscape of genetic interactions between gene expression quantitative trait loci. Our results reveal that allele-specific interactions, in which a gene only exerts an influence on the phenotype in the presence of a particular allele at ...[more]

PMID: 19223586

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Project description:BackgroundThe oral and pharyngeal jaw of cichlid fishes are a classic example of evolutionary modularity as their functional decoupling boosted trophic diversification and contributed to the success of cichlid adaptive radiations. Most studies until now have focused on the functional, morphological, or genetic aspects of cichlid jaw modularity. Here we extend this concept to include transcriptional modularity by sequencing whole transcriptomes of the two jaws and comparing their gene coexpression networks.ResultsWe show that transcriptional decoupling of gene expression underlies the functional decoupling of cichlid oral and pharyngeal jaw apparatus and the two units are evolving independently in recently diverged cichlid species from Lake Tanganyika. Oral and pharyngeal jaw coexpression networks reflect the common origin of the jaw regulatory program as there is high preservation of gene coexpression modules between the two sets of jaws. However, there is substantial rewiring of genetic architecture within those modules. We define a global jaw coexpression network and highlight jaw-specific and species-specific modules within it. Furthermore, we annotate a comprehensive in silico gene regulatory network linking the Wnt and AHR signalling pathways to jaw morphogenesis and response to environmental cues, respectively. Components of these pathways are significantly differentially expressed between the oral and pharyngeal jaw apparatus.ConclusionThis study describes the concerted expression of many genes in cichlid oral and pharyngeal jaw apparatus at the onset of the independent life of cichlid fishes. Our findings suggest that - on the basis of an ancestral gill arch network-transcriptional rewiring may have driven the modular evolution of the oral and pharyngeal jaws, highlighting the evolutionary significance of gene network reuse. The gene coexpression and in silico regulatory networks presented here are intended as resource for future studies on the genetics of vertebrate jaw morphogenesis and trophic adaptation.

Dataset Information

Modularity and interactions in the genetics of gene expression.

Publications

Modularity and interactions in the genetics of gene expression.

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