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Researchers combine molecular biology and math models to investigate variation in gene activity

National Science Foundation : 22 December, 2005  (Company News)
A population of genetically identical cells can exhibit random differences or 'noise' in gene activity that may ultimately contribute to differences in the physical characteristics of the so-called 'identical' cells. Such noise, which chimes in when cellular activity is out of sync among a population of cells, has been a nuisance to scientists studying the role genes play in a number of processes.
Now, Jeff Hasty at the University of California, San Diego has used advanced molecular biology techniques coupled with sophisticated mathematical models to tease apart the components that make up this noise, which appears to be involved in development, evolution and even some genetic conditions.

Hasty and his UCSD colleagues report their findings in the Dec. 22 issue of the journal Nature.

Joanne Tornow, the National Science Foundation program manager for this work said, 'Hasty's results epitomize the synergy created by interdisciplinary research. In this case, knowledge about a basic biological process advanced greatly when a physicist [Hasty] applied his expertise to a question seemingly unrelated to his field of training.'

The genome, we have all heard, is an organism's blueprint for life, but scientists are finding more to the story. Identical twins growing up in the same house, for example, can look and behave differently. Noisy gene expression, or variation in how cells process information when genes are turned on, provides part of the explanation.

The team used advanced computer programs to rigorously analyze the variation in gene activity in strains of yeast that were engineered to produce a green fluorescence on demand. By making cell-to-cell comparisons of fluorescence levels, the researchers were able to measure the effect of variation, or noise, on a population of genetically identical cells.

Hasty's group proved the dominant source of variability in gene expression in this experiment was extrinsic, that is, caused by factors not directly related to the expression process for the particular gene. Researchers typically thought that extrinsic variability was a consequence of random environmental fluctuations in or near the cell, but Hasty's results demonstrated that variable gene expression occurred because individual cells in a population are at various stages of their growth cycle.

The variability resulting from noise is a source of diversity in an otherwise identical population of cells, and diversity facilitates adaptability to environmental changes and potential evolutionary advantages. Alternatively, as a multi-celled organism develops, noise may send one or more genetically identical cells down different paths that may result in different physical characteristics.
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