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Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions.

ABSTRACT: Genetic regulatory networks (GRNs) have been widely studied, yet there is a lack of understanding with regards to the final size and properties of these networks, mainly due to no network currently being complete. In this study, we analyzed the distribution of GRN structural properties across a large set of distinct prokaryotic organisms and found a set of constrained characteristics such as network density and number of regulators. Our results allowed us to estimate the number of interactions that complete networks would have, a valuable insight that could aid in the daunting task of network curation, prediction, and validation. Using state-of-the-art statistical approaches, we also provided new evidence to settle a previously stated controversy that raised the possibility of complete biological networks being random and therefore attributing the observed scale-free properties to an artifact emerging from the sampling process during network discovery. Furthermore, we identified a set of properties that enabled us to assess the consistency of the connectivity distribution for various GRNs against different alternative statistical distributions. Our results favor the hypothesis that highly connected nodes (hubs) are not a consequence of network incompleteness. Finally, an interaction coverage computed for the GRNs as a proxy for completeness revealed that high-throughput based reconstructions of GRNs could yield biased networks with a low average clustering coefficient, showing that classical targeted discovery of interactions is still needed.

SUBMITTER: Campos AI

PROVIDER: S-EPMC6403251 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions.

Campos Adrian I AI Freyre-González Julio A JA

Scientific reports 20190306 1

Genetic regulatory networks (GRNs) have been widely studied, yet there is a lack of understanding with regards to the final size and properties of these networks, mainly due to no network currently being complete. In this study, we analyzed the distribution of GRN structural properties across a large set of distinct prokaryotic organisms and found a set of constrained characteristics such as network density and number of regulators. Our results allowed us to estimate the number of interactions t ...[more]

PMID: 30842463

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Project description:BACKGROUND: The structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression. RESULTS: We observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization. CONCLUSIONS: Albeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates that modularity may be a general feature of biological gene regulatory networks.

Project description:In situ adaptation to climate change will be critical for the persistence of many ectotherm species due to their relative lack of dispersal capacity. Climate change is causing increases in both the mean and the variance of environmental temperature, each of which may act as agents of selection on different traits. Importantly, these traits may not be heritable or have the capacity to evolve independently from one another. When genetic constraints prevent the "baseline" values of thermal performance traits from evolving rapidly, phenotypic plasticity driven by gene expression might become critical. We review the literature for evidence that thermal performance traits in ectotherms are heritable and have genetic architectures that permit their unconstrained evolution. Next, we examine the relationship between gene expression and both the magnitude and duration of thermal stress. Finally, we identify genes that are likely to be important for adaptation to a changing climate and determine whether they show patterns consistent with thermal adaptation. Although few studies have measured narrow-sense heritabilities of thermal performance traits, current evidence suggests that the end points of thermal reaction norms (tolerance limits) are moderately heritable and have the potential to evolve rapidly. By contrast, performance at intermediate temperatures has substantially lower evolutionary potential. Moreover, evolution in many species appears to be constrained by genetic correlations such that populations can adapt to either increases in mean temperature or temperature variability, but not both. Finally, many species have the capacity for plastic expression of the transcriptome in response to temperature shifts, with the number of differentially expressed genes increasing with the magnitude, but not the duration, of thermal stress. We use these observations to develop a conceptual model that describes the likely trajectory of genome evolution in response to changes in environmental temperature. Our results indicate that extreme weather events, rather than gradual increases in mean temperature, are more likely to drive genetic and phenotypic change in wild ectotherms.

Dataset Information

Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions.

Publications

Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions.

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