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PubMed2007

Black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens.

The evolution of bacterial pathogens from nonpathogenic ancestors is marked principally by the acquisition of virulence gene clusters on plasmids and pathogenicity islands via horizontal gene transfer. The flip side of this evolutionary force is the equally important adaptation of the newly minted pathogen to its new host niche. Pathoadaptive mutations take the form of modification of gene expression such that the pathogen is better fit to survive within the new niche. This mini-review describes the concept of pathoadaptation by loss of gene function. In this process, genes that are no longer compatible with the novel lifestyle of the pathogen are selectively inactivated either by point mutation, insertion, or deletion. These genes are called 'antivirulence genes'. Selective pressure sometimes leads to the deletion of large regions of the genome that contain antivirulence genes generating 'black holes' in the pathogen genome. Inactivation of antivirulence genes leads to a pathogen that is highly adapted to its host niche. Identification of antivirulence genes for a particular pathogen can lead to a better understanding of how it became a pathogen and the types of genetic traits that need to be silenced in order for the pathogen to colonize its new host niche successfully.

Adaptation, Biological↗
PubMed2000

Genetics. Transposons help sculpt a dynamic genome.

New research is showing that the mobile genetic elements called transposons cause more extensive restructuring of the genome than previously thought. Researchers have known for about 20 years that transposons can expand the genome, resulting in the repetitive DNA sequences sometimes called "junk," but the new work indicates that transposons can also contribute to substantial DNA losses. What's more, these changes can be rapid--at least on an evolutionary scale--and may help organisms adapt to their environments.

Adaptation, Physiological↗
PubMed1995

Importance of historical contingency in the stereochemistry of hydratase-dehydratase enzymes.

There are two stereochemical classes of hydratase-dehydratase enzymes. Those that catalyze the addition of water to alpha, beta-unsaturated thioesters give syn addition-elimination stereochemistry, whereas those that catalyze the addition of water to conjugated carboxylate substrates give anti stereochemistry. This dichotomy could reflect different adaptive advantages or contingencies of separate evolutionary histories. Determination of the nonenzymatic stereochemistry of deuterium oxide addition to fumarate and to S-crotonyl N-acetylcysteamine has provided direct evidence for the importance of the contingencies of evolutionary history, rather than chemical efficiency, in the pathways of these hydratase-dehydratase enzymes.

Biological Evolution↗
PubMed2005

Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

Animals↗
PubMed1997

The neuropathogenesis of Borna disease virus infections.

The unique genetic and biological properties of this small enveloped RNA virus indicate that Borna disease virus (BDV) is an evolutionary old pathogen. It appears perfectly adapted to persist inside the limbic system, a most delicate and sensitive old area of the mammalian brain involved in the control of mood, behavior, and memory. In many infected individuals, BDV remains a commensal during their lifetime. In a minority of vulnerable subjects, BDV becomes frequently activated, leading to episodes of distinct, more or less severe disturbances of information processing, behavioral and mood alterations. BDV research in humans is anticipated to initiate new insights into the interplay of exogenous and endogenous factors governing mood disorders. In nature BDV preferentially behaves as a neurotropic virus, but may latently and/or persistently infect cells of the reticuloendothelial system. This has been shown to be of great diagnostic importance, because now BDV 'footprints' can be followed in vivo in animals and man. BDV, which has long been considered as a classical animal virus, is present in humans, and has been found to be associated with some defined psychiatric disorders in particularly vulnerable individuals. An interaction of BDV proteins with neurotransmitter activities is plausible in the light of experimental animal data. Interference with normal behavior and the influence on mood and cognitive functions as demonstrated in animals and assumed in humans require extensive future research on the molecular etiopathogenesis. Aside from these clinical aspects, BDV is an unusual agent with outstanding features, namely replication in the nucleus of its target cells by an elusive, partially unknown mechanism, showing no cytopathogenicity or disturbance of vital cell functions, but altering luxury functions, and with a lifelong persistence giving rise to periods of long latency and short activation.

Animals↗
PubMed2000

Adaptive linkage crossover.

Problem-specific knowledge is often implemented in search algorithms using heuristics to determine which search paths are to be explored at any given instant. As in other search methods, utilizing this knowledge will more quickly lead a genetic algorithm (GA) towards better results. In many problems, crucial knowledge is not found in individual components, but in the interrelations between those components. For such problems, we develop an interrelation (linkage) based crossover operator that has the advantage of liberating GAs from the constraints imposed by the fixed representations generally chosen for problems. The strength of linkages between components of a chromosomal structure can be explicitly represented in a linkage matrix and used in the reproduction step to generate new individuals. For some problems, such a linkage matrix is known a priori from the nature of the problem. In other cases, the linkage matrix may be learned by successive minor adaptations during the execution of the evolutionary algorithm. This paper demonstrates the success of such an approach for several problems.

Algorithms↗
PubMed2001

A convergence analysis of unconstrained and bound constrained evolutionary pattern search.

We present and analyze a class of evolutionary algorithms for unconstrained and bound constrained optimization on R(n): evolutionary pattern search algorithms (EPSAs). EPSAs adaptively modify the step size of the mutation operator in response to the success of previous optimization steps. The design of EPSAs is inspired by recent analyses of pattern search methods. We show that EPSAs can be cast as stochastic pattern search methods, and we use this observation to prove that EPSAs have a probabilistic, weak stationary point convergence theory. This convergence theory is distinguished by the fact that the analysis does not approximate the stochastic process of EPSAs, and hence it exactly characterizes their convergence properties.

Algorithms↗
PubMed1999

Kennel enrichment: exercise and socialization of dogs.

In the last 50 years, there has been a growing need for storage and management systems for the production and maintenance of large numbers of dogs. Unwanted dogs and strays, detained in kennels, stay for various lengths of time. Large kennels also produce dogs for sale as companion animals, for the service dog industry (police and guide dogs), for biomedical research, and for use by dog food companies. Across the United States, literally tens of thousands of dogs are born in kennels and spend their lives in kennels. The laboratory dog, the kennel dog, the service dog, and the companion dog are in an evolutionary transition period, accompanied by concomitant adaptation to stresses signaled by a high frequency of genetic disease and behavioral abnormalities. For kennel enrichment programs, such as socialization and exercise, the modern kenneled dog is a genetically moving target. Specific recommendations apply neither to all breeds nor to the variations within a single breed.

Journal Article↗
PubMed2001

What do the MMPI scales fundamentally measure? Some hypotheses.

I consider the question of whether all psychopathological behaviors can, on an evolutionary foundation, be considered as positive adaptations. I proposed that higher functions can be differentiated from their associated emotional modulations at simultaneous subjective, behavioral, and neural levels and that organizing analyses in this way will enable us to fill in our understanding of both the effects and relief of traumatic experiences. I then present each of the 8 clinical scales of the MMPI (Hathaway & McKinley, 1943) as a dimension of positive adaptation with simultaneous cognitive-emotional, operant-classical, and neocortical-limbic elements. A variety of life-experience paradigms are then offered to explain the factors that operate to increase MMPI scale elevations as well as countermeasures that can operate to reduce such elevations. Understanding all such behaviors as adaptive leads to a notable enhancement of empathy.

Antisocial Personality Disorder↗
PubMed1995

Biological research on sexual orientation: a critique of the critics.

Evolutionary biologists are tired of being accused of being too biologically deterministic, by critics who have little understanding of what biological or evolutionary theories actually imply. Misunderstandings came about because social-science disciplines often do not share evolutionary biology's tendency to build into their models multiple "normal" paths of development. Sociobiologists first explained homosexuality adaptively because they first try to explain everything adaptively. Most nonbiologists are unaware of this very strong evolutionary tradition. It is now fashionable to discount scientific objectivity, but there are many examples of where such an attack is unwarranted. Kinsey produced a nontypological theory of sexual orientation in spite of his history as a taxonomist. Sociobiologists produced a nonpathological explanation of nonreproductive homosexuality in spite of the centrality of reproductive success in their models. In judging whether a discipline is particularly likely to be misused in social debates, one must perform the appropriate intellectual "controls". One must examine appropriate uses as well as misuses, and one must examine other disciplines to see whether there are differences in the relative likelihood of abuse. Indeed, many social-science theories have been even more clearly abused than biological ones.

Animals↗
PubMed2004

[Illusions: a window into perception].

Perception is the active construction of a neural state that correlates with biologically relevant elements present in the environment. This correlation, far from affording a one-to-one mapping, nonetheless guides our actions towards adaptive behaviors, thus being forged under evolutionary constraints. Since the construction of a percept is an intrinsically ambiguous process, perceptual discrepancies can arise from identical stimulation patterns. The recognition of these discrepancies is termed illusion, which originates, however, from the same physiological mechanisms that ordinarily lead to standard perception. Emanating from different sources, such as optical, sensory and cognitive factors, visual illusions are useful tools in accessing the physiological basis of perceptual processes and their interaction with motor planning and execution. Here we examine the biological roots of visual illusions and their interplay with some neurobiological, philosophical and esthetical issues.

Form Perception↗
PubMed1980

Sociobiology: another biological determinism.

Sociobiology is a form of biological determinism which argues that human social organization is constrained by genes that have been selected in evolution. In particular, it regards male dominance, hierarchical society, entrepreneurial economic activity, territoriality, and aggression as a consequences of human genes. It is shown that sociobiological theory is carefully constructed to make it impossible to test, that it makes a number of fundamental errors in attempting to describe "human nature," that there is no evidence for inheritance of human social traits, and that the evolutionary arguments used are merely fanciful, adaptive stories.

Animals↗
PubMed2002

Genetics of obesity and type 2 diabetes: tracking pathogenic traits during the predisease period.

The modern generalization of sedentary life and caloric abundance has created new physiological conditions capable of changing the level of expression of a number of genes involved in fuel metabolism and body weight regulation. It is likely that the genetic variants or alleles of these genes have in the past participated in the adaptation of human physiology to its evolutionary constraints. The nature and prevalence of polymorphisms responsible for the quantitative variation of complex metabolic traits may have been different among human populations, depending on their environment and ancestral genetic background. These polymorphisms could likely explain differences in disease susceptibility and prevalence among groups of humans. From complex traits to potentially complex alleles, understanding the molecular genetic basis underlying quantitative variation will continue to be a growing concern among geneticists dealing with obesity and type 2 diabetes, the main fuel disorders of the modern era. Genomics and genetic epidemiology now allow high-level linkage and association studies to be designed. But the pooling of large trans-geographic cohorts may in fact increase the genetic heterogeneity of studied traits and dilute genotype-phenotype associations. In this article, we underscore the importance of selecting the traits to be subjected to quantitative genetic analysis. Although this is not possible for most other multifactorial diseases, obesity and type 2 diabetes can be subjected to a pregenetic dissection of complexity into simpler quantitative traits (QTs). This dissection is based on the pathogenic mechanisms, and the time course of the traits, and the individuals' age, within the predisease period rather than on descriptive parameters after disease diagnosis. We defend that this approach of phenotypes may ease future associations to be established between QTs of intermediate complexity and genetic polymorphisms.

Diabetes Mellitus↗
PubMed2005

Experimental evidence for multivariate stabilizing sexual selection.

Stabilizing selection is a fundamental concept in evolutionary biology. In the presence of a single intermediate optimum phenotype (fitness peak) on the fitness surface, stabilizing selection should cause the population to evolve toward such a peak. This prediction has seldom been tested, particularly for suites of correlated traits. The lack of tests for an evolutionary match between population means and adaptive peaks may be due, at least in part, to problems associated with empirically detecting multivariate stabilizing selection and with testing whether population means are at the peak of multivariate fitness surfaces. Here we show how canonical analysis of the fitness surface, combined with the estimation of confidence regions for stationary points on quadratic response surfaces, may be used to define multivariate stabilizing selection on a suite of traits and to establish whether natural populations reside on the multivariate peak. We manufactured artificial advertisement calls of the male cricket Teleogryllus commodus and played them back to females in laboratory phonotaxis trials to estimate the linear and nonlinear sexual selection that female phonotactic choice imposes on male call structure. Significant nonlinear selection on the major axes of the fitness surface was convex in nature and displayed an intermediate optimum, indicating multivariate stabilizing selection. The mean phenotypes of four independent samples of males, from the same population as the females used in phonotaxis trials, were within the 95% confidence region for the fitness peak. These experiments indicate that stabilizing sexual selection may play an important role in the evolution of male call properties in natural populations of T. commodus.

Analysis of Variance↗
PubMed2006

Functional origins of fitness effect-sizes of compensatory mutations in the DNA bacteriophage phiX174.

Epistasis is an important and poorly understood aspect of mutations and strongly influences the evolutionary impact of genetic variation on adaptation and fitness. Although recent studies have begun to characterize the distribution of epistatic effects between mutations affecting fitness, there is currently a lack of empirical information on the underlying biological causes of these epistatic interactions. What are the functional constraints that determine the effectiveness of a compensatory mutation at restoring fitness? We have measured the effect-sizes of 52 compensatory mutations affecting nine different deleterious mutations in the major capsid and spike proteins of the DNA bacteriophage phiX174. On average, an experimentally detectable compensatory mutation recovers about two-thirds of the fitness cost of the preceding deleterious mutation. Variation in fitness effect-sizes is only weakly associated with measures of the distance separating the deleterious and compensatory mutations in the amino acid sequence or the folded protein structure. However, there is a strong association of fitness effect-size with the correlation in the effects of the mutations on the biochemical properties of amino acids. A compensatory mutation has the largest effect-size, on average, when both the compensatory and deleterious mutations have radical effects on the overall biochemical make-up of the amino acids. By examining the relative contributions of specific biochemical properties to variation in fitness effect-size, we find that the area and charge of amino acids have a major influence, which suggests that the complexity of the amino acid phenotype is simplified by selection into a reduced number of phenotypic components.

Bacteriophage phi X 174↗