Physiological epistasis, ontogenetic conflict and natural selection on physiology and life history

Ontogenetic conflict arises when optima for alleles governingfitness variation differ between juveniles and adults or betweenadult sexes. Loci that govern development of alternative phenotypesin the sexes, hereafter termed morph-determining loci, mediatedevelopment through the endocrine system. Morphotypic selectionis defined to be multivariate selection favoring discrete alternativemorphotypes (e.g., optima). When the optimal combinations ofalleles for alternative morphs differ between the sexes, itgenerates conflicting selection pressure and thus ontogeneticconflict. Selection on morph alleles promotes ontogenetic conflictbecause it perturbs physiological epistasis that governs theexpression of male versus female traits. Expression of physiologicaltraits arises from homeostasis that maintains trait expressionwithin a normal range. The genetic basis of homeostasis is likelyto arise from interactions among several genes (e.g., geneticepistasis) or protein products (e.g., physiological epistasis).For example, endocrine regulation arises from interactions betweengondatropins, which are protein hormones produced by the hypothalamic-pituitaryglands, and steroid hormones, which are produced by the gonads(e.g., HPG axis). The side-blotched lizard system is discussedwith respect to physiological bases of ontogenetic conflict.We also describe a novel molecular marker strategy for uncoveringgenome-wide physiological epistasis in nature. Finally, ontogeneticconflict exerts selection on females to evolve mate selectionor cryptic choice that is reflected in different sires beingchosen for son versus daughter production. We describe how side-blotchedlizard females ameliorate ontogenetic conflict by cryptic choiceof male genotypes to produce sons versus daughters.     

Hypoxic Reptiles: Blood Gases, Body Temperature and Control of Breathing

Our contribution to this symposium is a review of recent modelsand experimental cdata on oxygen homeostasis in vertebrateswith normal intracardiac shunts; i.e., amphibians and reptiles.We focus on the interactions among hemoglobin function, bodytemperature regulation, and cardiovascular shunts under normalconditions (i.e., breathing fresh air at or near sea level)and during external hypoxia (e.g., altitude, burrows) and internalhypoxia (e.g., anemia, hemorrhage). Mathematical models andexperimental data suggest that animals with venous admixturefrom cardiovascular shunts will show biphasic arterial and mixedvenous Po₂ responses to warming; i.e., first increasing andthen, as the dissociation curve shifts too far to the right,decreasing. This has implications for many physiological functionsincluding oxygen consumption by tissues, control of breathing,as well as preferred body temperature and its regulation. Wepresent some of the recent experiments that have explored theseimplications.     

Cellular sociology regulates the hierarchical spatial patterning and organization of cells in organisms

Advances in single-cell biotechnology have increasingly revealed interactions of cells with their surroundings, suggesting a cellular society at the microscale. Similarities between cells and humans across multiple hierarchical levels have quantitative inference potential for reaching insights about phenotypic interactions that lead to morphological forms across multiple scales of cellular organization, namely cells, tissues and organs. Here, the functional and structural comparisons between how cells and individuals fundamentally socialize to give rise to the spatial organization are investigated. Integrative experimental cell interaction assays and computational predictive methods shape the understanding of societal perspective in the determination of the cellular interactions that create spatially coordinated forms in biological systems. Emerging quantifiable models from a simpler biological microworld such as bacterial interactions and single-cell organisms are explored, providing a route to model spatio-temporal patterning of morphological structures in humans. This analogical reasoning framework sheds light on structural patterning principles as a result of biological interactions across the cellular scale and up.     

Biomechanics of the lung parenchyma: critical roles of collagen and mechanical forces.

The biomechanical properties of connective tissues play fundamental roles in how mechanical interactions of the body with its environment produce physical forces at the cellular level. It is now recognized that mechanical interactions between cells and the extracellular matrix (ECM) have major regulatory effects on cellular physiology and cell-cycle kinetics that can lead to the reorganization and remodeling of the ECM. The connective tissues are composed of cells and the ECM, which includes water and a variety of biological macromolecules. The macromolecules that are most important in determining the mechanical properties of these tissues are collagen, elastin, and proteoglycans. Among these macromolecules, the most abundant and perhaps most critical for structural integrity is collagen. In this review, we examine how mechanical forces affect the physiological functioning of the lung parenchyma, with special emphasis on the role of collagen. First, we overview the composition of the connective tissue of the lung and their complex structural organization. We then describe how mechanical properties of the parenchyma arise from its composition as well as from the architectural organization of the connective tissue. We argue that, because collagen is the most important load-bearing component of the parenchymal connective tissue, it is also critical in determining the homeostasis and cellular responses to injury. Finally, we overview the interactions between the parenchymal collagen network and cellular remodeling and speculate how mechanotransduction might contribute to disease propagation and the development of small- and large-scale heterogeneities with implications to impaired lung function in emphysema.     

MODULARITY AND RATES OF EVOLUTIONARY CHANGE IN A POWER‐AMPLIFIED PREY CAPTURE SYSTEM

The dynamic interplay among structure, function, and phylogeny form a classic triad of influences on the patterns and processes of biological diversification. Although these dynamics are widely recognized as important, quantitative analyses of their interactions have infrequently been applied to biomechanical systems. Here we analyze these factors using a fundamental biomechanical mechanism: power amplification. Power‐amplified systems use springs and latches to generate extremely fast and powerful movements. This study focuses specifically on the power amplification mechanism in the fast raptorial appendages of mantis shrimp (Crustacea: Stomatopoda). Using geometric morphometric and phylogenetic comparative analyses, we measured evolutionary modularity and rates of morphological evolution of the raptorial appendage's biomechanical components. We found that “smashers” (hammer‐shaped raptorial appendages) exhibit lower modularity and 10‐fold slower rates of morphological change when compared to non‐smashers (spear‐shaped or undifferentiated appendages). The morphological and biomechanical integration of this system at a macroevolutionary scale and the presence of variable rates of evolution reveal a balance between structural constraints, functional variation, and the “roles of development and genetics” in evolutionary diversification.     

Emergent cell and tissue dynamics from subcellular modeling of active biomechanical processes

Cells and the tissues they form are not passive material bodies. Cells change their behavior in response to external biochemical and biomechanical cues. Behavioral changes, such as morphological deformation, proliferation and migration, are striking in many multicellular processes such as morphogenesis, wound healing and cancer progression. Cell-based modeling of these phenomena requires algorithms that can capture active cell behavior and their emergent tissue-level phenotypes. In this paper, we report on extensions of the subcellular element model to model active biomechanical subcellular processes. These processes lead to emergent cell and tissue level phenotypes at larger scales, including (i) adaptive shape deformations in cells responding to slow stretching, (ii) viscous flow of embryonic tissues, and (iii) streaming patterns of chemotactic cells in epithelial-like sheets. In each case, we connect our simulation results to recent experiments.     

Molecular Ecology of Teleost Fish Hemoglobins Strategies for Adapting to Changing Environments

Animals live in environments where physical chemical and biologicalparameters are continually changing. If homeostasis is to bemaintained animals must adapt. The respiratory complex (and specifically hemoglobins) is perhapsthe best system to use to study adaptation to environmentalstress because it exists at the organism environment interface.Fish are particularly useful in such studies since they responddirectly to such variables as temperature oxygen pH and salinity. Maintenance of respiratory homeostasis is achieved by a hostof molecular cellular and physiological mechanisms. The linkagebetween these molecular interactions the animals and the physicochemicalenvironment. I have termed Molecular Ecology. In the followingpaper I will consider some of these relationships.     

Morpho-histology and genotype dependence of in vitro morphogenesis in mature embryo cultures of wheat

Cellular totipotency is one of the basic principles of plant biotechnology. Currently, the success of the procedure used to produce transgenic plants is directly proportional to the successful insertion of foreign DNA into the genome of suitable target tissue/cells that are able to regenerate plants. The mature embryo (ME) is increasingly recognized as a valuable explant for developing regenerable cell lines in wheat biotechnology. We have previously developed a regeneration procedure based on fragmented ME in vitro culture. Before we can use this regeneration system as a model for molecular studies of the morphogenic pathway induced in vitro and investigate the functional links between regenerative capacity and transformation receptiveness, some questions need to be answered. Plant regeneration from cultured tissues is genetically controlled. Factors such as age/degree of differentiation and physiological conditions affect the response of explants to culture conditions. Plant regeneration in culture can be achieved through embryogenesis or organogenesis. In this paper, the suitability of ME tissues for tissue culture and the chronological series of morphological data observed at the macroscopic level are documented. Genetic variability at each step of the regeneration process was evaluated through a varietal comparison of several elite wheat cultivars. A detailed histological analysis of the chronological sequence of morphological events during ontogeny was conducted. Compared with cultures of immature zygotic embryos, we found that the embryogenic pathway occurs slightly earlier and is of a different origin in our model. Cytological, physiological, and some biochemical aspects of somatic embryo formation in wheat ME culture are discussed.     

Biomechanics and mechanobiology in functional tissue engineering

The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements.     

Evolutionary consequences of many-to-one mapping of jaw morphology to mechanics in labrid fishes

Many physiological traits consist of two hierarchically related levels: physical structures and the emergent functional properties of those structures. Because selection tends to act on the emergent functional traits, the evolution of structural phenotypes will depend on the nature of the form-function relationship. Complex physiological or biomechanical traits are often characterized by many-to-one mapping: numerous structural phenotypes can yield equivalent functions. We suggest that this redundancy can promote the evolution of phenotypic diversity, and we illustrate this effect with a combination of empirical and analytical studies of a complex biomechanical trait, the four-bar linkage found in the jaws of labrid fishes. We show that labrid jaws are subject to many-to-one mapping of form-to-jaw mechanical properties but that some mechanical types have higher levels of morphological redundancy than others. This variation in redundancy has affected the diversity and distribution of labrid jaw shapes: labrid species are disproportionately concentrated around functional traits with higher potential for redundancy. Many-to-one mapping can also mitigate evolutionary constraints imposed by mechanical trade-offs by allowing a species to simultaneously optimize multiple functional properties. Many-to-one mapping may be an important factor in generating the uneven patterns of diversity in physiological traits.     

A 3D Architectural and Process-based Model of Maize Development

A 3D architectural and process-based model of maize developmentwas implemented on the basis of the L-system software Graphtal,interfaced with physical models computing microclimate distributedon the 3D canopy structure. In a first step, we incorporatedin the software Graphtal additional functions that enable bi-directionalcommunication with external modules. A simple model for distributedphotosynthetically active radiation and the model for apex temperatureby Cellieret al. (Agricultural and Forest Meteorology63: 35–54,1993) were interfaced with Graphtal. In a second step we developeda L-system model for maize, where production rules for growthand development of organs are based on the current state ofknowledge of maize development as a function of temperature.Visual representation of the plant is based on the geometricalmodel of leaf shape by Prévot, Aries and Monestiez (Agronomie11:491–503, 1991). Finally, various data sets were used toevaluate the physiological aspects and the geometrical representation.It is concluded that environmental L-systems are a convenienttool to integrate biophysical processes from organ to canopylevel, and provide a framework to model growth of individualplants in relation to local conditions and ability to foragefor resources. However, progress is needed to improve both theknowledge of physiological processes at the organ level andthe calculation of physical environmental parameters; some directionsfor future research are proposed.Copyright 1998 Annals of BotanyCompany Growth model; 3D plant architecture;Zea maysL.; corn; temperature; L-system modelling; developmental physiology; virtual plant.     

Fluid–structure interaction (FSI) simulation for studying the impact of atherosclerosis on hemodynamics,arterial tissue remodeling,and initiation risk of intracranial aneurysms

The biomechanical and hemodynamic effects of atherosclerosis on the initiation of intracranial aneurysms (IA) are not yet clearly discovered. Also, studies for the observation of hemodynamic variation due to atherosclerotic stenosis and its impact on arterial remodeling and aneurysm genesis remain a controversial field of vascular engineering. The majority of studies performed are relevant to computational fluid dynamic (CFD) simulations. CFD studies are limited in consideration of blood and arterial tissue interactions. In this work, the interaction of the blood and vessel tissue because of atherosclerotic occlusions is studied by developing a fluid and structure interaction (FSI) analysis for the first time. The FSI presents a semi-realistic simulation environment to observe how the blood and vessels' structural interactions can increase the accuracy of the biomechanical study results. In the first step, many different intracranial vessels are modeled for an investigation of the biomechanical and hemodynamic effects of atherosclerosis in arterial tissue remodeling. Three physiological conditions of an intact artery, the artery with intracranial atherosclerosis (ICAS), and an atherosclerotic aneurysm (ACA) are employed in the models with required assumptions. Finally, the obtained outputs are studied with comparative and statistical analyses according to the intact model in a normal physiological condition. The results show that existing occlusions in the cross-sectional area of the arteries play a determinative role in changing the hemodynamic behavior of the arterial segments. The undesirable variations in blood velocity and pressure throughout the vessels increase the risk of arterial tissue remodeling and aneurysm formation.

     

Quantifying the sensitivity of barley seed germination to oxygen, abscisic acid, and gibberellin using a population-based threshold model

Barley (Hordeum vulgare L.) seeds (grains) exhibit dormancyat maturity that is largely due to the presence of the glumellae(hulls) that reduce the availability of oxygen (O₂) to the embryo.In addition, abscisic acid (ABA) and gibberellins (GAS) interactwith O₂ to regulate barley seed dormancy. A population-basedthreshold model was applied to quantify the sensitivities ofseeds and excised embryos to O₂, ABA, and GA, and to their interactiveeffects. The median O₂ requirement for germination of dormantintact barley seeds was 400-fold greater than for excised embryos,indicating that the tissues enclosing the embryo markedly limitO₂ penetration. However, embryo O₂ thresholds decreased by anotherorder of magnitude following after-ripening. Thus, increasesin both permeability of the hull to O₂ and embryo sensitivityto O₂ contribute to the improvement in germination capacityduring after-ripening. Both ABA and GA had relatively smalleffects on the sensitivity of germination to O₂, but ABA andGA thresholds varied over several orders of magnitude in responseto O₂ availability, with sensitivity to ABA increasing and sensitivityto GA decreasing with hypoxia. Simple additive models of O₂–ABAand O₂–GA interactions required consideration of theseO₂ effects on hormone sensitivity to account for actual germinationpatterns. These quantitative and interactive relationships amongO₂, ABA, and GA sensitivities provide insight into how dormancyand germination are regulated by a combination of physical (O₂diffusion through the hull) and physiological (ABA and GA sensitivities)factors. Key words: Abscisic acid, barley, germination, gibberellin, Hordeum vulgare L., model, oxygen, sensitivity Received 2 August 2007; Revised 14 November 2007 Accepted 19 November 2007