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Synchronization of stochastic expressions drives the clustering of functionally related genes.

ABSTRACT: Functionally related genes tend to be chromosomally clustered in eukaryotic genomes even after the exclusion of tandem duplicates, but the biological significance of this widespread phenomenon is unclear. We propose that stochastic expression fluctuations of neighboring genes resulting from chromatin dynamics are more or less synchronized such that their expression ratio is more stable than that for unlinked genes. Consequently, chromosomal clustering could be advantageous when the expression ratio of the clustered genes needs to stay constant, for example, because of the accumulation of toxic compounds when this ratio is altered. Evidence from manipulative experiments on the yeast GAL cluster, comprising three chromosomally adjacent genes encoding enzymes catalyzing consecutive reactions in galactose catabolism, unequivocally supports this hypothesis and elucidates how disorder in one biological phenomenon-gene expression noise-could prompt the emergence of order in another-genome organization.

SUBMITTER: Xu H

PROVIDER: S-EPMC6785257 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Synchronization of stochastic expressions drives the clustering of functionally related genes.

Xu Haiqing H Liu Jing-Jing JJ Liu Zhen Z Li Ying Y Jin Yong-Su YS Zhang Jianzhi J

Science advances 20191009 10

Functionally related genes tend to be chromosomally clustered in eukaryotic genomes even after the exclusion of tandem duplicates, but the biological significance of this widespread phenomenon is unclear. We propose that stochastic expression fluctuations of neighboring genes resulting from chromatin dynamics are more or less synchronized such that their expression ratio is more stable than that for unlinked genes. Consequently, chromosomal clustering could be advantageous when the expression ra ...[more]

PMID: 31633028

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Project description:BackgroundThe previous studies of genome-wide expression patterns show that a certain percentage of genes are cell cycle regulated. The expression data has been analyzed in a number of different ways to identify cell cycle dependent genes. In this study, we pose the hypothesis that cell cycle dependent genes are considered as oscillating systems with a rhythm, i.e. systems producing response signals with period and frequency. Therefore, we are motivated to apply the theory of multivariate phase synchronization for clustering cell cycle specific genome-wide expression data.ResultsWe propose the strategy to find groups of genes according to the specific biological process by analyzing cell cycle specific gene expression data. To evaluate the propose method, we use the modified Kuramoto model, which is a phase governing equation that provides the long-term dynamics of globally coupled oscillators. With this equation, we simulate two groups of expression signals, and the simulated signals from each group shares their own common rhythm. Then, the simulated expression data are mixed with randomly generated expression data to be used as input data set to the algorithm. Using these simulated expression data, it is shown that the algorithm is able to identify expression signals that are involved in the same oscillating process. We also evaluate the method with yeast cell cycle expression data. It is shown that the output clusters by the proposed algorithm include genes, which are closely associated with each other by sharing significant Gene Ontology terms of biological process and/or having relatively many known biological interactions. Therefore, the evaluation analysis indicates that the method is able to identify expression signals according to the specific biological process. Our evaluation analysis also indicates that some portion of output by the proposed algorithm is not obtainable by the traditional clustering algorithm with Euclidean distance or linear correlation.ConclusionBased on the evaluation experiments, we draw the conclusion as follows: 1) Based on the theory of multivariate phase synchronization, it is feasible to find groups of genes, which have relevant biological interactions and/or significantly shared GO slim terms of biological process, using cell cycle specific gene expression signals. 2) Among all the output clusters by the proposed algorithm, the cluster with relatively large size has a tendency to include more known interactions than the one with relatively small size. 3) It is feasible to understand the cell cycle specific gene expression patterns as the phenomenon of collective synchronization. 4) The proposed algorithm is able to find prominent groups of genes, which are not obtainable by traditional clustering algorithm.

Project description:Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its "preferred" frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions.

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Synchronization of stochastic expressions drives the clustering of functionally related genes.

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Synchronization of stochastic expressions drives the clustering of functionally related genes.

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