Population genetics approach to the problem of the nonspecific biological resistance of the human body. I. Statement of the problem and basis for the approach. Distribution parameters of anthropometric markers of normal and ill newborn infants and nurslings

Distributions of two metrical characters-the weight and the body length at birth are considered in several groups of healthy, diseased and dead newborns and infants. Significant differences in statistical parameters of these distributions (mean, standard deviation, skewness and kurtosis) are demonstrated for normal and malformated children. The increased number of children with minimal deviations from the mean values of characters (adaptive norm) is observed among healthy newborns, while in groups of diseased and dead children the frequency of individuals with extreme (especially low) values is increased. The principle of classification of individuals based simultaneously on two characteris is suggested and the problem of "average phenotype" classification by the number of characters is discussed.     

Comparison of the reactions of male and female Wistar rats. To 5-day exposure to 2G hypergravity

Number of essential distinctions between male and female rats both before and after 5-day exposure to 2g were observed. These distinctions are not simple quantitative. One gets an impression that males and females have various "strategies" of homeostasis maintenance in the norm and various patterns of adaptive reactions in different situations including 2g hypergravity.     

Human adaptive phenotypes in physiology and medicine]

The study of pathological and physiological features associated with genetic syndromes has gained increasing momentum over the past two decades. In this paper, the definition of adaptive phenotypes is presented and the complexities and obstacles to progress in this field are summarized. This is a problem of general biology and is related to genetic specificity of every organism. The concept of individual norm of man's responses is to a certain extent associated with the doctrine of constitutions. From the practical point of view it is suggested to use in medicine and physiology an individual-constitutional approach and the term adaptophenotype (adaptive phenotype) which means a stable complex of genetic and phenotypical characteristics. It can be determined using clinical, physiological, genealogical, and dermatoglyphic methods, methods of genetic markers, phenotypical analysis, etc. A variety of developmental and physiological characteristics can form the "adaptophenotype" is used in general application, it is used to refer to a broad range of human functioning including pathological characteristics (somatic disorders), psychopathology (mental disorders), physiological and behavior problems. Genetic approaches help reveal not only individual hereditary parameters which manifest as signs but also latent pathological and physiological characteristics that may be used for professional selection. The delineation of adaptive phenotypes is a difficult enterprise, not that should not dissuade clinicians and researchers from undertaking it.     

The relation between the variability of polygenic morphological and monogenic biochemical traits as exemplified by Karakul sheep

A quantitative method for investigation of relationship between polygenic and monogenic traits has been proposed. It is based on examination of relationship between frequencies of distribution classes of an adaptive quantitative trait and frequencies of certain genetic character in the same classes. The method permits to locate a gene marker within a space of quantitative trait values. Using adaptively significant morpho-anatomic traits, it is possible to estimate indirectly adaptive values of gene markers under consideration, since, in accordance with the concept of adaptive norm, "average" phenotypes have maximal fitness, whereas deviative phenotypes transgress the bounds of the optimum. As a genetical character, genotype of certain biochemical locus, individual heterozygosity range or interlocus combinations of alleles could be used. The method has been applied to newborn Astrakhan lambs. Principal component analysis has been used to obtain complex characterization for six constitutional characters. Some regularities in location of homo- and heterozygous genotypes of the transferrin locus within a space of morphological characters' values have been revealed.     

Towards a general theory of adaptive walks on rugged landscapes

Adaptive evolution, to a large extent, is a complex combinatorial optimization process. In this article we take beginning steps towards developing a general theory of adaptive "walks" via fitter variants in such optimization processes. We introduce the basic idea of a space of entities, each a 1-mutant neighbor of many other entities in the space, and the idea of a fitness ascribed to each entity. Adaptive walks proceed from an initial entity, via fitter neighbors, to locally or globally optimal entities that are fitter than their neighbors. We develop a general theory for the number of local optima, lengths of adaptive walks, and the number of alternative local optima accessible from any given initial entity, for the baseline case of an uncorrelated fitness landscape. Most fitness landscapes are correlated, however. Therefore we develop parts of a universal theory of adaptation on correlated landscapes by adaptive processes that have sufficient numbers of mutations per individual to "jump beyond" the correlation lengths in the underlying landscape. In addition, we explore the statistical character of adaptive walks in two independent complex combinatorial optimization problems, that of evolving a specific cell type in model genetic networks, and that of finding good solutions to the traveling salesman problem. Surprisingly, both show similar statistical features, encouraging the hope that a general theory for adaptive walks on correlated and uncorrelated landscapes can be found. In the final section we explore two limits to the efficacy of selection. The first is new, and surprising: for a wide class of systems, as the complexity of the entities under selection increases, the local optima that are attainable fall progressively closer to the mean properties of the underlying space of entities. This may imply that complex biological systems, such as genetic regulatory systems, are "close" to the mean properties of the ensemble of genomic regulatory systems explored by evolution. The second limit shows that with increasing complexity and a fixed mutation rate, selection often becomes unable to pull an adapting population to those local optima to which connected adaptive walks via fitter variants exist. These beginning steps in theory development are applied to maturation of the immune response, and to the problem of radiation and stasis. Despite the limitations of the adaptive landscape metaphor, we believe that further development along the lines begun here will prove useful.     

Estimation and prediction of functional changes in organisms in space flight

The article is devoted to theoretical and applied problems of estimation of the organism functional state and a level of health. Transitive states between health and illness, between norm and a pathology, so-called prenosological states are considered. The level of health is determined by adaptable opportunities of an organism, a degree of regulatory systems tension and their functional reserve. As the basic methodical approach to an estimation of a degree of regulatory systems tension the method of heart variability analysis is described. The applied aspect of a considered problem is submitted by results of the researches which have been carried out in conditions of space flight. Changes of organism functional state at different stages of adaptation to conditions of long weightlessness are described. The mathematical model of functional states is submitted. Four types of the vegetative regulation, differing on the adaptive reactions in conditions of space flight are allocated. Results of researches of crew members of the International space station are submitted.     

Hemo- and lymphomicrocirculatory bed of the broad ligament of the uterus in the presence of collateral circulation

Structural adaptation of the vascular bed in the broad ligament of the dog uterus has been studied at various time of the experimental phlebohypertension. Restitution of the circulation after the posterior vena cava occulsion occurs phasically. The venous collateralies are not formed at one time and it is connected with the venous pressure level in the inferiocaval system and with some changes in the construction of the microcirculatory bed. Basing on the morphometry data, a general equation has been derived which reflects dynamics of the microangiological parameters and demonstrates unidirectionness of the adaptive reactions in the vascular bed at the disturbed venous circulation. Using principles of the system-structural analysis and the mathematical graph theory, we consider the microcirculatory system of the broad ligament of the uterus as a graph-system and study the reorganization of the microcirculatory network at a venous congestion. Realization of the compensatory possibilities is reached in the microcirculatory bed by a changed relationships in the number of the intervascular connections. The latter are estimated according to the graph-schemes of the microvascular bed. Morphokinetics of the connections between the vessels is characterized by widening or narrowing the borders of the "adaptive norm" and by changing the microangioarchitectonics. At the same time, there is noted formation of specialized microhemoangioconstructions. Morphofunctional state of the lymphatic system is connected with reorganization of the angioarchitectonics. This is certain manifestation of the law of the lymphatic and blood beds "synergism". Thus, the structural changes of the vascular bed are aimed to support a certain hemodynamic level.     

Adaptation to spatially heterogeneous modifying and adaptive environments

The development of an individual's phenotype is influenced by environmental factors (the modifying environment) which may differ from those factors (the adaptive environment) that decide on the adaptational value of the developed phenotype. The shapes of adaptationally optimal norms of reaction are therefore essentially determined by associations between these two environmental components together with the degree of adaptational sensitivity of the developed phenotypes. Two complementary aspects of optimality are accounted for: (a) environments can be optimal for a given norm of reaction and (b) norms of reaction can be optimal for a given environment. The results are obtained for random distribution of genotypes over environmental conditions and under the physiologically reasonable premise that fitness is a function of the costs of modification and adaptation. It turned out that the associations of adaptive and modifying environments are the primary sources of adaptational optimization. More specifically, it is shown that (i) independence between the two environmental components constitutes an adaptationally optimal environment only for norms of reaction in which all phenotypes are adaptively insensitive; (ii) if costs of modification do not depend on the environment, and if the two environmental components are not associated, adaptationally optimal norms of reaction can always be realized through phenogenetic invariance; (iii) as a rule, adaptively sensitive phenotypes developed under strong environmental associations necessitate phenogenetic plasticity for the optimal norm of reaction; (iv) a norm of reaction which is adaptationally optimal in its adaptationally optimal environment can always be realized through phenogenetic invariance, if costs of modification do not vary with the environment. These results reveal an important role of patterns of adaptive sensitivity of phenotypes, which may even surpass that of shapes of norms of reaction in adaptational processes.     

Genetic evolution,plasticity, and bet‐hedging as adaptive responses to temporally autocorrelated fluctuating selection: A quantitative genetic model

Adaptive responses to autocorrelated environmental fluctuations through evolution in mean reaction norm elevation and slope and an independent component of the phenotypic variance are analyzed using a quantitative genetic model. Analytic approximations expressing the mutual dependencies between all three response modes are derived and solved for the joint evolutionary outcome. Both genetic evolution in reaction norm elevation and plasticity are favored by slow temporal fluctuations, with plasticity, in the absence of microenvironmental variability, being the dominant evolutionary outcome for reasonable parameter values. For fast fluctuations, tracking of the optimal phenotype through genetic evolution and plasticity is limited. If residual fluctuations in the optimal phenotype are large and stabilizing selection is strong, selection then acts to increase the phenotypic variance (bet‐hedging adaptive). Otherwise, canalizing selection occurs. If the phenotypic variance increases with plasticity through the effect of microenvironmental variability, this shifts the joint evolutionary balance away from plasticity in favor of genetic evolution. If microenvironmental deviations experienced by each individual at the time of development and selection are correlated, however, more plasticity evolves. The adaptive significance of evolutionary fluctuations in plasticity and the phenotypic variance, transient evolution, and the validity of the analytic approximations are investigated using simulations.     

The problem of adaptive individual choice in cultural evolution

This paper tries to explain how individuals manage adaptive individual choice (i.e., the decision to acquire a fitter than average behavior or idea rapidly and tractably) in cultural evolution, despite the fact that acquiring fitness information is very difficult. I argue that the means of solving this problem suggested in the cultural evolution literature largely are various types of decision rules employing representations of fitness correlated properties or states of affairs. I argue that the problem of adaptive individual choice is best solved where some of these learning rule representations are socially transmitted and some are biologically transmitted.

Physiological phenotypes of immune resistance and their significance in assessment of health level

The health status was assessed in virtually healthy residents of the Far East south by the parameters describing the organism’s resistance on the integration level of the immune system and systems of lipid peroxidation and antioxidant protection (LPO-AOP). New data on the immunophysiological mechanisms in the development of the regional adaptive norm of immune system and LPO-AOP of cell membranes are presented. System analysis showed that the immunophysiological norm in the population was presented by eight main functional phenotypes of immune resistance: resistant, T-hyposuppressor, T-helper, resistant and nonresistant T-suppressor, compensated and subcompensated hyporesistant, and deficient. The prospects of immune resistance phenotype determination for the assessment of individual and population health level are discussed. The concept presented is a theoretical base for a new approach to the health assessment which deals with diagnostics and the early prevention of premorbid disorders considering the regional dynamic stereotype of physiological functions.     

Evolution and maintenance of the environmental component of the phenotypic variance: benefit of plastic traits under changing environments

How environmental variances in quantitative traits are influenced by variable environments is an important problem in evolutionary biology. In this study, the evolution and maintenance of phenotypic variance in a plastic trait under stabilizing selection are investigated. The mapping from genotypic value to phenotypic value of the quantitative trait is approximated by a linear reaction norm, with genotypic effects on its phenotypic mean and sensitivity to environment. The environmental deviation is assumed to be decomposed into environmental quality, which interacts with genotypic value, and residual developmental noise, which is independent of genotype. Environmental quality and the optimal phenotype of stabilizing selection are allowed to randomly fluctuate in both space and time, and individuals migrate equally before development and reproduction among different niches. Analyses show that phenotypic plasticity is adaptive within variable environments if correlations have become established between the optimal phenotype and environmental quality in space and/or time. The evolved plasticity increases with variances in optimal phenotypes and correlations between optimal phenotype and environmental quality; this further induces increases in mean fitness and the environmental variance in the trait. Under certain circumstances, however, the environmental variance may decrease with increase in variation in environmental quality.     

Biometeorological norm as tolerance interval of man to weather stimuli

The paper discusses the problem of a biometeorological norm as the tolerance interval of the human organism to weather stimuli. The methodical approach is based on the normal distribution of variables. In this study thermal sensation (Effective Temperature) and daily numbers of traffic accidents were correlated. The results confirm the weak stimulus effect of meteorological conditions when they lie within the normal ±0.0 to ±1.5 standard deviation range.     

Rapid adaptive divergence of life-history traits in response to abiotic stress within a natural population of a parthenogenetic nematode

Sexual reproduction is acknowledged to facilitate adaptation to novel environments while asexual eukaryotes are often regarded as having low adaptive potential. This view has been challenged in a number of studies, but the adaptive potential of asexual populations in the field is poorly documented. We investigated the response of natural populations of the parthenogenetic nematode Acrobeloides nanus to imposed divergent selective pressures. For this purpose, we employed a replicated evolution experiment in the field. After 20 years of evolution under abiotic stress and control conditions, life-history traits were assessed in reaction norm- and reciprocal transplant experiments. Both these experiments indicated adaptive divergence within the population of A. nanus. Namely, the transplant experiment demonstrated that in the stressed soil environment, body growth rate was more reduced in the nematodes originating from the control treatment. In the reaction norm experiment, survival and reproduction were higher under test conditions corresponding to the native environment of the nematodes. The differences in the analysed traits are discussed in the context of life-history theory. Overall, our results strongly support high adaptive potential of A. nanus and suggest that population structure and distribution of asexual species is shaped by local adaptation events.     

Accurate computation of the stable solitary wave for the FitzHugh-Nagumo equations

Comparisons are made between three different methods for computing the stable solitary wave solution for the FitzHugh-Nagumo equations which consist of a nonlinear diffusion equation coupled to an ordinary differential equation in time. They model the Hodgkin-Huxley equations which describe the propagation of the nerve impulse down the axon. Two of the methods involve the travelling wave equations. Previous accurate numerical computations of these equations as an initial-value problem using a shooting method lead to inaccurate values for the wave speed; however, nonlinear corrections to the initial values are shown to yield accurate values. A boundary-value method applies asymptotic boundary conditions and uses a spline-collocation code called COLSYS for numerical solution of boundary-value problems which leads to accurate wave profiles and speeds. The third method is to solve an initial-boundary-value problem with an adaptive outgoing wave condition for the partial differential equations where the solitary wave emerges as the stable long time solution. The concept of a wave integral is introduced and they are derived to determine the wave speed used in the adaptive boundary condition and to measure the closeness of the computed solutions to the exact solitary wave solution.This work was supported in part by the Natural Sciences and Engineering Research Council Canada under Grant A4559 and by the John Simon Guggenheim Memorial Foundation     

Patterns in the transition from normal to neurosis in dogs with different typological traits in food and defensive situations

At comparison of the formation of neurosis in dogs with different typological characteristics in conditions with alimentary and pain reinforcement, a resemblance was revealed of transition from norm to the initial stage of pathology. In strong animals a development was seen of compensatory tachycardia at circular changes of conditioned activity. Weak type dogs are characterized by a lowering or full disappearance of reflexes in combination with bradycardia. The method of differentiation, allowing in situations with alimentary reinforcement to classify the tested animals according to the type of higher nervous activity and differentiate the states of "norm" and "initial stage of neurosis", proved to be effective for the analogous aims also in studies with defensive reinforcement.     

Reaction norms for metamorphic traits in natterjack toads to larval density and pond duration

The evolution of environmentally-induced changes in phenotype or reaction norm implies both the existence at some time of genetic variation within a population for that plasticity measured by the presence of genotype x environment interaction (G x E), and that phenotypic variation affects fitness. Otherwise, the genetic structure of polygenic traits may restrict the evolution of the reaction norm by the lack of independent evolution of a given trait in different environments or by genetic trade-offs with other traits that affect fitness. In this paper, we analyze the existence of G x E in metamorphic traits to two environmental factors, larval density and pond duration in a factorial experiment with Bufo calamita tadpoles in semi-natural conditions and in the laboratory. Results showed no plastic temporal response in metamorphosis to pond durability at low larval density. The rank of genotypes did not change across different hydroperiods, implying a high genetic correlation that may constrain the evolution of the reaction norm. At high larval density a significant G x E interaction was found, suggesting the potential for the evolution of the reaction norm. A sibship (#1) attained the presumed “optimal” reaction norm by accelerating developmental rate in short duration ponds and delaying it in longer ponds. This could be translated in fitness by an increment in metamorphic survival and size at metamorphosis in short and long ponds respectively with respect to non-plastic sibships. However, genetic variability for plasticity suggests that optimal reaction norm for developmental rates may be variable and hard to achieve in the heterogeneous pond environment. Mass at metamorphosis was not plastic across different pond durations but decreased at high larval density. Significant adaptive plasticity for growth rates appeared in environments that differed drastically in level of crowding conditions, both in the field and in the laboratory. The fact that survival of juveniles metamorphosed at high density ponds was a monotonic function of metamorphic size, implies that response to selection may occur in this population of natterjacks and that genetic variability in plasticity may be a reliable mechanism maintaining adaptive genetic variation in growth rates in the highly variable pond environment.     

Characteristics of the motor potentials in disorders of the subcortical motor structures of the human brain

Properties of motor potentials (MPs) were studied in patients with disturbance of function of subcortical motor structures--disturbance causing parkinsonism manifestations. MPs components are singled out preceding movement--"readiness potential" (N1), "motor potential" (N2) and MP components which are electrophysiological correlates of realization processes (component P2) and movement completion (component N3). It is revealed that MPs in patients with parkinsonism are changed in comparison with the norm; the most significant differences are observed in components N1, P2, N3, what is expressed in prolongation and a certain amplitude decrease of these components. Amplitude-temporal parameters most similar to the norm belong to the component N2, which is considered as an electrophysiological correlate of movement triggering. A hypothesis is suggested on its cortical origin.     

Individual variation in the development of the common toad, Bufo bufo (Anura, Bufonidae): 2. Diagnostic characters of the axial skeleton

Analysis of individual variation in diagnostic characters of the axial skeleton has been performed in all offspring (1633 ind.) from the same spawn of one pair of common toads under conditions of laboratory rearing, with natural elimination being reduced to a minimum. More than 50 skeletal anomalies have been recorded. Factual data are presented that characterize deviations from the species norm in the frequency of “background anomalies” (Kovalenko, 2003). Correlations between manifestations of different variants of character states are considered. The problem of norm and anomaly in individual variation is discussed.     

Mirror brain systems, concepts and language: the price for anthropogenesis

The paper discusses the problem of cognitive evolution and the basis for the origin of language and mind, genetic history of Homo sapiens and whether the basic concepts are inborn or effected by experience, sensory or cognitive per se. The problem of localization of higher functions and Theory of Mind in norm and pathology is analyzed.