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Dissecting dynamic genetic variation that controls temporal gene response in yeast.

ABSTRACT: Inter-individual variation in regulatory circuits controlling gene expression is a powerful source of functional information. The study of associations among genetic variants and gene expression provides important insights about cell circuitry but cannot specify whether and when potential variants dynamically alter their genetic effect during the course of response. Here we develop a computational procedure that captures temporal changes in genetic effects, and apply it to analyze transcription during inhibition of the TOR signaling pathway in segregating yeast cells. We found a high-order coordination of gene modules: sets of genes co-associated with the same genetic variant and sharing a common temporal genetic effect pattern. The temporal genetic effects of some modules represented a single state-transitioning pattern; for example, at 10-30 minutes following stimulation, genetic effects in the phosphate utilization module attained a characteristic transition to a new steady state. In contrast, another module showed an impulse pattern of genetic effects; for example, in the poor nitrogen sources utilization module, a spike up of a genetic effect at 10-20 minutes following stimulation reflected inter-individual variation in the timing (rather than magnitude) of response. Our analysis suggests that the same mechanism typically leads to both inter-individual variation and the temporal genetic effect pattern in a module. Our methodology provides a quantitative genetic approach to studying the molecular mechanisms that shape dynamic changes in transcriptional responses.

SUBMITTER: Brodt A

PROVIDER: S-EPMC4256076 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Dissecting dynamic genetic variation that controls temporal gene response in yeast.

Brodt Avital A Botzman Maya M David Eyal E Gat-Viks Irit I

PLoS computational biology 20141204 12

Inter-individual variation in regulatory circuits controlling gene expression is a powerful source of functional information. The study of associations among genetic variants and gene expression provides important insights about cell circuitry but cannot specify whether and when potential variants dynamically alter their genetic effect during the course of response. Here we develop a computational procedure that captures temporal changes in genetic effects, and apply it to analyze transcription ...[more]

PMID: 25474467

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Project description:Sandy beach ecological theory states that physical features of the beach control macrobenthic community structure on all but the most dissipative beaches. However, few studies have simultaneously evaluated the relative importance of physical, chemical and biological factors as potential explanatory variables for meso-scale spatio-temporal patterns of intertidal community structure in these systems. Here, we investigate macroinfaunal community structure of a micro-tidal sandy beach that is located on an oligotrophic subtropical coast and is influenced by seasonal estuarine input. We repeatedly sampled biological and environmental variables at a series of beach transects arranged at increasing distances from the estuary mouth. Sampling took place over a period of five months, corresponding with the transition between the dry and wet season. This allowed assessment of biological-physical relationships across chemical and nutritional gradients associated with a range of estuarine inputs. Physical, chemical, and biological response variables, as well as measures of community structure, showed significant spatio-temporal patterns. In general, bivariate relationships between biological and environmental variables were rare and weak. However, multivariate correlation approaches identified a variety of environmental variables (i.e., sampling session, the C?N ratio of particulate organic matter, dissolved inorganic nutrient concentrations, various size fractions of photopigment concentrations, salinity and, to a lesser extent, beach width and sediment kurtosis) that either alone or combined provided significant explanatory power for spatio-temporal patterns of macroinfaunal community structure. Overall, these results showed that the macrobenthic community on Mtunzini Beach was not structured primarily by physical factors, but instead by a complex and dynamic blend of nutritional, chemical and physical drivers. This emphasises the need to recognise ocean-exposed sandy beaches as functional ecosystems in their own right.

Dataset Information

Dissecting dynamic genetic variation that controls temporal gene response in yeast.

Publications

Dissecting dynamic genetic variation that controls temporal gene response in yeast.

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