Variability in gene expression underlies incomplete penetrance
The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also gene...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/76649 |
| _version_ | 1826195851728388096 |
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| author | van Oudenaarden, Alexander Rifkin, Scott A. Raj, Arjun Andersen, Erik C. |
| author2 | Massachusetts Institute of Technology. Department of Physics |
| author_facet | Massachusetts Institute of Technology. Department of Physics van Oudenaarden, Alexander Rifkin, Scott A. Raj, Arjun Andersen, Erik C. |
| author_sort | van Oudenaarden, Alexander |
| collection | MIT |
| description | The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation. |
| first_indexed | 2024-09-23T10:16:34Z |
| format | Article |
| id | mit-1721.1/76649 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:16:34Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/766492022-09-26T16:55:16Z Variability in gene expression underlies incomplete penetrance van Oudenaarden, Alexander Rifkin, Scott A. Raj, Arjun Andersen, Erik C. Massachusetts Institute of Technology. Department of Physics van Oudenaarden, Alexander Rifkin, Scott A. Raj, Arjun Andersen, Erik C. The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation. National Institutes of Health (U.S.). Pioneer Award Mathematical Sciences Postdoctoral Research Fellowships (DMS-0603392) National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (5F32GM080966) 2013-01-30T15:44:43Z 2013-01-30T15:44:43Z 2010-02 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/76649 Raj, Arjun et al. “Variability in Gene Expression Underlies Incomplete Penetrance.” Nature 463.7283 (2010): 913–918. en_US http://dx.doi.org/10.1038/nature08781 Nature Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | van Oudenaarden, Alexander Rifkin, Scott A. Raj, Arjun Andersen, Erik C. Variability in gene expression underlies incomplete penetrance |
| title | Variability in gene expression underlies incomplete penetrance |
| title_full | Variability in gene expression underlies incomplete penetrance |
| title_fullStr | Variability in gene expression underlies incomplete penetrance |
| title_full_unstemmed | Variability in gene expression underlies incomplete penetrance |
| title_short | Variability in gene expression underlies incomplete penetrance |
| title_sort | variability in gene expression underlies incomplete penetrance |
| url | http://hdl.handle.net/1721.1/76649 |
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