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Access through your institution Buy or subscribe The authors' hypothesis was that the variable phenotypic outcome of a mutation is caused by stochastic, inter-individual expression
variation in the genetic interaction partners of the mutated gene. To examine this theory, fluorescent transcriptional reporter genes were used to relate gene expression variation during
early development to later phenotypes. Specifically, the authors examined variation in the larval phenotype caused by mutations in _tbx-9_, which encodes a T box transcription factor: ~50%
of larvae that are homozygous for a null _tbx-9_ allele have muscular and epidermal defects, whereas the remainder develop normally. The penetrance of _tbx-9_-null mutations is reduced when
_tbx-8_, an ancestral duplicate of _tbx-9_, is experimentally overexpressed. This buffering feedback mechanism was quantified at the expression and phenotypic level in embryos with
endogenous levels of _tbx-8_ expression: in _tbx-9_ mutants, _tbx-8_ transcription is upregulated ~1.6-fold in early development, and the degree of this upregulation correlates with the
degree of masking of the _tbx-9_ mutant defects. The same phenotypic compensation mechanism was seen between another pair of ancestral gene duplicates: those encoding the zinc finger
transcription factors FLH-1 and FLH-2. Together, these two examples support the idea that, in early development, variation in the expression of one gene contributes to the incomplete
penetrance of mutations in the other. They also indicate that ancient gene duplicates might be under selective pressure to be retained owing to their canalizing role in development. This is
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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support ORIGINAL RESEARCH PAPER * Burga, A., Casanueva, M. O.
& Lehner, B. Predicting mutation outcome from early stochastic variation in genetic interaction partners. _Nature_ 480, 250–255 (2011) Article CAS Google Scholar Download references
Authors * Tanita Casci View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS
ARTICLE Casci, T. Genetic support network to the rescue. _Nat Rev Genet_ 13, 74 (2012). https://doi.org/10.1038/nrg3154 Download citation * Published: 20 December 2011 * Issue Date: February
2012 * DOI: https://doi.org/10.1038/nrg3154 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not
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