Modeling Genomes to Phenomes to Populations in a Changing Climate: The Need for Collaborative Networks

Condensed Abstract Climate is changing globally and its impacts can arise at different levels of biological organization; yet, cross-level consequences of climate change are still poorly understood. Designing effective environmental management and adaptation plans requires implementation of mechanistic models that span the biological hierarchy. Because biological systems are inherently complex and dynamic in nature, dealing with complexities efficiently necessitates simplification of systems or approximation of relevant processes, but there is little consensus on mathematical approaches to scale from genes to populations. Here we present an effort that aims to bring together groups that often do not interact, but that are essential to illuminating the complexities of life: empirical scientists and mathematical modelers, spanning levels of biological organization from genomes to organisms to populations. Through interplay between theory, models, and data, we aim to facilitate the generation of a new synthesis and a conceptual framework for biology across levels

Cytoskeletal Regulation Dominates Temperature-Sensitive Proteomic Changes of Hibernation in Forebrain of 13-Lined Ground Squirrels

<div><p>13-lined ground squirrels, <i>Ictidomys tridecemlineatus</i>, are obligate hibernators that transition annually between summer homeothermy and winter heterothermy – wherein they exploit episodic torpor bouts. Despite cerebral ischemia during torpor and rapid reperfusion during arousal, hibernator brains resist damage and the animals emerge neurologically intact each spring. We hypothesized that protein changes in the brain underlie winter neuroprotection. To identify candidate proteins, we applied a sensitive 2D gel electrophoresis method to quantify protein differences among forebrain extracts prepared from ground squirrels in two summer, four winter and fall transition states. Proteins that differed among groups were identified using LC-MS/MS. Only 84 protein spots varied significantly among the defined states of hibernation. Protein changes in the forebrain proteome fell largely into two reciprocal patterns with a strong body temperature dependence. The importance of body temperature was tested in animals from the fall; these fall animals use torpor sporadically with body temperatures mirroring ambient temperatures between 4 and 21°C as they navigate the transition between summer homeothermy and winter heterothermy. Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly resembled the homeotherms, indicating that the changes observed in torpid hibernators are defined by body temperature, not torpor per se. Metabolic enzymes were largely unchanged despite varied metabolic activity across annual and torpor-arousal cycles. Instead, the majority of the observed changes were cytoskeletal proteins and their regulators. While cytoskeletal structural proteins tended to differ seasonally, i.e., between summer homeothermy and winter heterothermy, their regulatory proteins were more strongly affected by body temperature. Changes in the abundance of various isoforms of the microtubule assembly and disassembly regulatory proteins dihydropyrimidinase-related protein and stathmin suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy during torpor-arousal cycles.</p></div

Significant pathway enrichments in squirrel forebrain for two primary hierarchical clusters.

<p>Note. Hierarchical Cluster 1, with seven significantly enriched functional annotation clusters, contains proteins decreased in cold T_b, whereas hierarchical Cluster 2, with two significant functional annotation clusters, contains proteins increased at cold T_b, and decreased during euthermy (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071627#pone-0071627-g002" target="_blank">Fig. 2</a>). Enrichment score gives the mean <i>p</i>-value among members of each annotation cluster (negative log). Enrichment data were calculated by DAVID Bioinformatics Resources v6.7 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071627#pone.0071627-Huang1" target="_blank">[25]</a>.</p

The fall proteome tracks body temperature.

<p>Fall transition individuals were held in warm (T_a = 18–20°C, #41–46) or cold rooms (T_a = 4°C, #47–52). (A) Unsupervised classification of all states using the most important predictors determined in Fig. 3A maintains the segregation of states by T_b. The mixed physiology of Fall animals can test the effect of T_b. (B) Unsupervised classification quantified proximity of FT individuals based on the defined groups as training data. In all but three individuals, more than 50% of the FT proteome was similar to summer or spring euthermic ground squirrels (x-axis: animal ID). The three exceptions were cold torpid (* denotes torpid), and instead had proteomes more proximate to LT/EAr. The absence of a similar pattern in the two warm-housed but torpid individuals (T_b = 18–21°C), supports the hypothesis that the LT/EAr proteome is defined by T_b, and not torpor per se. (C) Proximity to the euthermic groups (SA+SpC+IBA) correlates significantly with T_b.</p

Sampled states of the hibernator’s year were defined by body temperature.

<p>Samples were collected from 7 states. Summer (SA, n = 6) and spring (SpC, n = 5) ground squirrels represented the homeothermic portions of the annual cycle. Winter states representing the heterothermic period (blue box, expanded for clarity) were collected throughout the winter hibernation season and were defined as follows by body temperature telemetry: entering torpor (Ent, n = 7) at 27°C>T_b >23°C; late torpor (LT, n = 7) at 80–95% previous bout duration; early arousing (EAr, n = 6) at 7°Cb <12.8°C; and 3–4 hours after T_b stabilized in inter-bout arousal (IBA, n = 5) period. Samples were also collected during the highly variable Fall transition period (FT, n = 12) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0071627#pone.0071627-Russell1" target="_blank">[16]</a>. Colors representing each state are used throughout.</p

Modeling Genomes to Phenomes to Populations in a Changing Climate: The Need for Collaborative Networks

Condensed Abstract Climate is changing globally and its impacts can arise at different levels of biological organization; yet, cross-level consequences of climate change are still poorly understood. Designing effective environmental management and adaptation plans requires implementation of mechanistic models that span the biological hierarchy. Because biological systems are inherently complex and dynamic in nature, dealing with complexities efficiently necessitates simplification of systems or approximation of relevant processes, but there is little consensus on mathematical approaches to scale from genes to populations. Here we present an effort that aims to bring together groups that often do not interact, but that are essential to illuminating the complexities of life: empirical scientists and mathematical modelers, spanning levels of biological organization from genomes to organisms to populations. Through interplay between theory, models, and data, we aim to facilitate the generation of a new synthesis and a conceptual framework for biology across levels