General statistics of stochastic process of gene expression in eukaryotic cells.
Thousands of genes are expressed at such very low levels (< or =1 copy per cell) that global gene expression analysis of rarer transcripts remains problematic. Ambiguity in identification of rarer transcripts creates considerable uncertainty in fundamental questions such as the total number of genes expressed in an organism and the biological significance of rarer transcripts. Knowing the distribution of the true number of genes expressed at each level and the corresponding gene expression level probability function (GELPF) could help resolve these uncertainties. We found that all observed large-scale gene expression data sets in yeast, mouse, and human cells follow a Pareto-like distribution model skewed by many low-abundance transcripts. A novel stochastic model of the gene expression process predicts the universality of the GELPF both across different cell types within a multicellular organism and across different organisms. This model allows us to predict the frequency distribution of all gene expression levels within a single cell and to estimate the number of expressed genes in a single cell and in a population of cells. A random "basal" transcription mechanism for protein-coding genes in all or almost all eukaryotic cell types is predicted. This fundamental mechanism might enhance the expression of rarely expressed genes and, thus, provide a basic level of phenotypic diversity, adaptability, and random monoallelic expression in cell populations.
Laboratory of Integrative and Medical Biophysics, National Institute of Child Health and Human Development/NIH, Bldg. 13, Rm. 3W16, Bethesda, MD 20892-5772, USA. vk28u@nih.gov
V A
VA
Kuznetsov
G D
GD
Knott
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RF
Bonner
D000818:Animals; D002460:Cell Line; D005057:Eukaryotic Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D013269:Stochastic Processes; D014158:Transcription, Genetic