An eco-evo-devo genetic network model of stress response.

The capacity of plants to resist abiotic stresses is of great importance to agricultural, ecological and environmental sustainability, but little is known about its genetic underpinnings. Existing genetic tools can identify individual genetic variants mediating biochemical, physiological, and cellular defenses, but fail to chart an overall genetic atlas behind stress resistance. We view stress response as an eco-evo-devo process by which plants adaptively respond to stress through complex interactions of developmental canalization, phenotypic plasticity, and phenotypic integration. As such, we define and quantify stress response as the developmental change of adaptive traits from stress-free to stress-exposed environments. We integrate composite functional mapping and evolutionary game theory to reconstruct omnigenic, information-flow interaction networks for stress response. Using desert-adapted Euphrates poplar as an example, we infer salt resistance-related genome-wide interactome networks and trace the roadmap of how each SNP acts and interacts with any other possible SNPs to mediate salt resistance. We characterize the previously unknown regulatory mechanisms driving trait variation; i.e. the significance of a SNP may be due to the promotion of positive regulators, whereas the insignificance of a SNP may result from the inhibition of negative regulators. The regulator-regulatee interactions detected are not only experimentally validated by two complementary experiments, but also biologically interpreted by their encoded protein-protein interactions. Our eco-evo-devo model of genetic interactome networks provides an approach to interrogate the genetic architecture of stress response and informs precise gene editing for improving plants' capacity to live in stress environments.

A quantitative decision theory of animal conflict.

Interactions between individuals are thought to shape evolution and speciation through natural selection, but little is known about how an individual (or player) strategically interacts with others to maximize its payoff. We develop a simple decision-theoretic model that generates four hypotheses about the choice of an optimal behavioral strategy by a player in response to the strategies of other players. The golden threshold hypothesis suggests that 62% is the critical threshold determining the transition of a larger player's strategy in reaction to its smaller dove-like partner. Below this critical point, the larger one exploits the smaller one, whereas above it, the larger one chooses to cooperate with the smaller one. The competition-to-cooperation shift hypothesis states that a larger player never cooperates with a smaller hawk-like player unless the former is reversely surpassed in size by the latter by 75%. The Fibonacci retracement mark hypothesis proposes that, faced with a larger dove-like player, a smaller player chooses to either cooperate or cheat, depending on whether its size relative to the larger player is less or more than 38%. The surrender-resistance hypothesis suggests that, in reaction to a larger hawk-like player, a smaller player can either gain some benefit from resistance or is sacrificed by choosing to surrender. We test these hypotheses by re-analyzing body mass data of full-sib fishes that were co-cultured in a common water pool. Pairwise analysis of these co-existing fishes broadly suggests the prediction of our hypotheses. Taken together, our model unveils detectable yet previously unknown quantitative mechanisms that mediate the strategic choice of animal behavior in populations or communities. Given the ubiquitous nature of biological interactions occurring at different levels of organizations and the paucity of quantitative approaches to understand them, results by our decision-theoretic model represent an initial step towards the deeper understanding of how biological entities interact with each other to drive their evolution.

Modeling genome-wide by environment interactions through omnigenic interactome networks.

How genes interact with the environment to shape phenotypic variation and evolution is a fundamental question intriguing to biologists from various fields. Existing linear models built on single genes are inadequate to reveal the complexity of genotype-environment (G-E) interactions. Here, we develop a conceptual model for mechanistically dissecting G-E interplay by integrating previously disconnected theories and methods. Under this integration, evolutionary game theory, developmental modularity theory, and a variable selection method allow us to reconstruct environment-induced, maximally informative, sparse, and casual multilayer genetic networks. We design and conduct two mapping experiments by using a desert-adapted tree species to validate the biological application of the model proposed. The model identifies previously uncharacterized molecular mechanisms that mediate trees' response to saline stress. Our model provides a tool to comprehend the genetic architecture of trait variation and evolution and trace the information flow of each gene toward phenotypes within omnigenic networks.

A behavioral model for mapping the genetic architecture of gut-microbiota networks.

The gut microbiota may play an important role in affecting human health. To explore the genetic mechanisms underlying microbiota-host relationships, many genome-wide association studies have begun to identify host genes that shape the microbial composition of the gut. It is becoming increasingly clear that the gut microbiota impacts host processes not only through the action of individual microbes but also their interaction networks. However, a systematic characterization of microbial interactions that occur in densely packed aggregates of the gut bacteria has proven to be extremely difficult. We develop a computational rule of thumb for addressing this issue by integrating ecological behavioral theory and genetic mapping theory. We introduce behavioral ecology theory to derive mathematical descriptors of how each microbe interacts with every other microbe through a web of cooperation and competition. We estimate the emergent properties of gut-microbiota networks reconstructed from these descriptors and map host-driven mutualism, antagonism, aggression, and altruism QTLs. We further integrate path analysis and mapping theory to detect and visualize how host genetic variants affect human diseases by perturbing the internal workings of the gut microbiota. As the proof of concept, we apply our model to analyze a published dataset of the gut microbiota, showing its usefulness and potential to gain new insight into how microbes are organized in human guts. The new model provides an analytical tool for revealing the "endophenotype" role of microbial networks in linking genotype to end-point phenotypes.

SEGN: Inferring real-time gene networks mediating phenotypic plasticity.

The capacity of an organism to alter its phenotype in response to environmental perturbations changes over developmental time and is a process determined by multiple genes that are co-expressed in intricate but organized networks. Characterizing the spatiotemporal change of such gene networks can offer insight into the genomic signatures underlying organismic adaptation, but it represents a major methodological challenge. Here, we integrate the holistic view of systems biology and the interactive notion of evolutionary game theory to reconstruct so-called systems evolutionary game networks (SEGN) that can autonomously detect, track, and visualize environment-induced gene networks along the time axis. The SEGN overcomes the limitations of traditional approaches by inferring context-specific networks, encapsulating bidirectional, signed, and weighted gene-gene interactions into fully informative networks, and monitoring the process of how networks topologically alter across environmental and developmental cues. Based on the design principle of SEGN, we perform a transcriptional plasticity study by culturing Euphrates poplar, a tree that can grow in the saline desert, in saline-free and saline-stress conditions. SEGN characterize previously unknown gene co-regulation that modulates the time trajectories of the trees' response to salt stress. As a marriage of multiple disciplines, SEGN shows its potential to interpret gene interdependence, predict how transcriptional co-regulation responds to various regimes, and provides a hint for exploring the mass, energetic, or signal basis that drives various types of gene interactions.

A Drive to Driven Model of Mapping Intraspecific Interaction Networks.

Community ecology theory suggests that an individual's phenotype is determined by the phenotypes of its coexisting members to the extent at which this process can shape community evolution. Here, we develop a mapping theory to identify interaction quantitative trait loci (QTL) governing inter-individual dependence. We mathematically formulate the decision-making strategy of interacting individuals. We integrate these mathematical descriptors into a statistical procedure, enabling the joint characterization of how QTL drive the strengths of ecological interactions and how the genetic architecture of QTL is driven by ecological networks. In three fish full-sib mapping experiments, we identify a set of genome-wide QTL that control a range of societal behaviors, including mutualism, altruism, aggression, and antagonism, and find that these intraspecific interactions increase the genetic variation of body mass by about 50%. We showcase how the interaction QTL can be used as editors to reconstruct and engineer new social networks for ecological communities.

Interrogation of Internal Workings in Microbial Community Assembly: Play a Game through a Behavioral Network?

Increasing evidence shows that the influence of microbiota on biogeochemical cycling, plant development, and human health is executed through a complex network of microbe-microbe interactions. However, characterizing how microbes interact and work together within closely packed and highly heterogeneous microbial ecosystems is extremely challenging. Here, we describe a rule-of-thumb framework for visualizing polymicrobial interactions and extracting general principles that underlie microbial communities. We integrate elements of metabolic ecology, behavioral ecology, and game theory to quantify the interactive strategies by which microbes at any taxonomic level compete for resources and cooperate symbiotically with each other to form and stabilize ecological communities. We show how the framework can chart an omnidirectional landscape of microbial cooperation and competition that may drive various natural processes. This framework can be implemented into genome-wide association studies to unravel the genetic mechanisms underlying microbial interaction networks and their evolutionary consequences along spatiotemporal gradients.IMPORTANCE Identifying general biological rules that underlie the complexity and heterogeneity of microbial communities has proven to be highly challenging. We present a rule-of-thumb framework for studying and characterizing how microbes interact with each other across different taxa to determine community behavior and dynamics. This framework is computationally simple but conceptually meaningful, and it can provide a starting point to generate novel biological hypotheses about microbial interactions and explore internal workings of microbial community assembly in depth.