Paper: Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait

Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic
Trait
Juliet Ansel1,2,3, Hélène Bottin1,2,3, Camilo Rodriguez-Beltran4, Christelle
Damon1,2,3, Muniyandi Nagarajan1,2,3, Steffen Fehrmann1,2,3, Jean François4,
Gaël Yvert1,2,3,4

1 Université de Lyon, Lyon, France2 Laboratoire de Biologie Moléculaire de
la Cellule, Ecole Normale Supérieure de Lyon, CNRS, Lyon, France3 IFR128
BioSciences Lyon-Gerland, Lyon, France4 Laboratoire de Biotechnologie et
Bioprocédés, Institut National des Sciences Appliquées, Toulouse, France

Abstract
The genetic control of common traits is rarely deterministic, with many
genes contributing only to the chance of developing a given phenotype. This
incomplete penetrance is poorly understood and is usually attributed to
interactions between genes or interactions between genes and environmental
conditions. Because many traits such as cancer can emerge from rare events
happening in one or very few cells, we speculate an alternative and
complementary possibility where some genotypes could facilitate these events
by increasing stochastic cell-to-cell variations (or 'noise'). As a very
first step towards investigating this possibility, we studied how natural
genetic variation influences the level of noise in the expression of a
single gene using the yeast S. cerevisiae as a model system. Reproducible
differences in noise were observed between divergent genetic backgrounds. We
found that noise was highly heritable and placed under a complex genetic
control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL)
of noise, one locus being explained by an increase in noise when
transcriptional elongation was impaired. Our results suggest that the level
of stochasticity in particular molecular regulations may differ between
multicellular individuals depending on their genotypic background. The
complex genetic architecture of noise buffering couples genetic to
non-genetic robustness and provides a molecular basis to the probabilistic
nature of complex traits.

Source: PLoS Genetics [Open Access]
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000049

Comment:
The Discussion is particularly enlightening and relevant to Evolutionary
Biology.

Posted by
Robert Karl Stonjek


.

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