RESUMO
Zygosity of diploid genome (i.e., degree to which two parental alleles of a gene have varied genetic sequences) adds another dimension to stochastic gene expression. The allelic imbalance in chromatin accessibility or divergence in regulatory sequences leads to fitness effects but the quantitative aspects thereof are largely left unexplored. We investigate diploid gene expression systems with homozygous (the same) and heterozygous (varied) combination of alleles in cis-regulatory sequences, not in structural gene loci, and characterize the zygosity-associated stochastic fluctuations in protein abundance. An emerging feat of heterozygosity is its counterintuitive capacity for genetic noise control. Especially when the noise is dominantly contributed to by the fluctuations in duty cycle ("reliability") rather than in process speed ("productivity") of gene expression machinery, its interallelic discrepancy acts to reduce the gene expression noise. These findings offer a novel insight into the rich repertoire of balancing selection enriched in the regulatory elements of immune response genes.
Assuntos
Cromatina , Regulação da Expressão Gênica , Alelos , Expressão Gênica , HeterozigotoRESUMO
Despite stochastic fluctuations, some genetic switches are able to retain their expression states through multiple cell divisions, providing epigenetic memory. We propose a novel rationale for tuning the functional stability of a simple synthetic gene switch through protein dimerization. Introducing an approximation scheme to access long-time stochastic dynamics of multiple-component gene circuits, we find that the spontaneous switching rate may exhibit greater than 8 orders of magnitude variation. The manipulation of the circuit's biochemical properties offers a practical strategy for designing robust epigenetic memory with synthetic circuits.
Assuntos
DNA/genética , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Modelos Genéticos , DNA/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Dimerização , Cinética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Processos EstocásticosRESUMO
We investigate the kinetic roughening of Ar+ ion-sputtered Pd(001) surface both experimentally and theoretically. In situ real-time x-ray reflectivity and in situ scanning tunneling microscopy show that nanoscale adatom islands form and grow with increasing sputter time t. Surface roughness W(t) and lateral correlation length xi(t) follow the scaling laws W(t) approximately t(beta) and xi(t) approximately t(1/z) with the exponents beta approximately 0.20 and 1/z approximately 0.20, for an ion beam energy epsilon=0.5 keV, which is inconsistent with the prediction of the Kuramoto-Sivashinsky (KS) model. We thereby extend the KS model by applying the coarse-grained continuum approach of the Sigmund theory to the order of O(inverted Delta(4),h(2)), where h is the surface height, and derive a new term of the form inverted Delta(2)(inverted Delta h)(2) which plays a decisive role in describing the observed morphological evolution of the sputtered surface.