Macroscopic variations are routinely observed in the genetically identical cells of organisms ranging in complexity from bacteria to mammals. "Watchmakers can neither make individual watches with intrinsically perfect accuracy, nor perfectly synchronize any two watches to eliminate extrinsic variations," said Hasty. "And intrinsic and extrinsic variation in gene expression also prevents genetically identical cells growing side-by-side from ticking in unison."
Intrinsic noise resulting from low copy numbers of molecules has been the focus of earlier studies by Hasty's group. Its Nature paper focuses on extrinsic noise, an even larger source of variation between identical cells growing side-by-side in identical conditions. "This extrinsic noise originates from cells being out of phase in their growth cycle," said Hasty. "It's unavoidable. This study also established an 'extrinsic-noise floor' in 11 genes for which intrinsic noise is negligible."
The group measured the noise floor by used genetically engineered strains of yeast with a green fluorescence marker linked to a gene involved in the metabolism of the sugar galactose. The galactose gene and 10 others were chosen because they are expressed in yeast cells in high copy numbers, a feature that makes intrinsic noise in their expression statistically insignificant. By making cell-to-cell comparisons of the activation of the galactose-fluorescence gene pair in experiments with one to five copies of the gene pair per cell, the team was able to measure the extrinsic-noise floor, a parameter that is needed to create a mathematical algorithm describing gene-expression variation in yeast.
"This may sound relatively straightforward: extrinsic variability is due to individual cells growing out of phase with one another," said Hasty. "However, this study is the first rigorous description of this
Source:University of California - San Diego