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Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?

BACKGROUND: Medical and pre-professional health students ask questions about human health that can be answered in two ways, by giving proximate and evolutionary explanations. Proximate explanations, most common in textbooks and classes, describe the immediate scientifically known biological mechanisms of anatomical characteristics or physiological processes. These explanations are necessary but insufficient. They can be complemented with evolutionary explanations that describe the evolutionary processes and principles that have resulted in human biology we study today. The main goal of the science of Darwinian Medicine is to investigate human disease, disorders, and medical complications from an evolutionary perspective. DISCUSSION: This paper contrasts the differences between these two types of explanations by describing principles of natural selection that underlie medical questions. Thus, why is human birth complicated? Why does sickle cell anemia exist? Why do we show symptoms like fever, diarrhea, and coughing when we have infection? Why do we suffer from ubiquitous age-related diseases like arteriosclerosis, Alzheimer's and others? Why are chronic diseases like type II diabetes and obesity so prevalent in modern society? Why hasn't natural selection eliminated the genes that cause common genetic diseases like hemochromatosis, cystic fibrosis, Tay sachs, PKU and others? SUMMARY: In giving students evolutionary explanations professors should underscore principles of natural selection, since these can be generalized for the analysis of many medical questions. From a research perspective, natural selection seems central to leading hypotheses of obesity and type II diabetes and might very well explain the occurrence of certain common genetic diseases like cystic fibrosis, hemochromatosis, Tay sachs, Fragile X syndrome, G6PD and others because of their compensating advantages. Furthermore, armed with evolutionary explanations, health care professionals can bring practical benefits to patients by treating their symptoms of infection more specifically and judiciously. They might also help curtail the evolutionary arms race between pathogens and antibiotic defenses.

Adaptation, Biological↗

Evolution and the American social sciences: An evolutionary social scientist's view.

American social scientists rarely ever use evolutionary concepts to explain behavior, despite the potential of such concepts to elucidate major social problems. I argue that this observation can be understood as the product of three influences: an ideologically narrowed political liberalism; a fear of ''Social Darwinism'' as a scientific idea, rather than a scientific apostasy; and a widely believed criticism of evolutionary thinking as deterministic, reductionistic, and Panglossian. I ask what is to be done to encourage social scientists to learn and to apply evolutionary lessons. I answer with four solutions. First, evolutionary social scientists should more effectively educate their non-evolutionary students and colleagues. Second, they should publicize, even popularize, accessible refutations of perennially misleading criticisms. Third, they should more credibly assure skeptics that evolutionary theory not only keeps the ''social'' in social science but better explains social behavior than can any individual-level theory, such as rational-choice theory. Fourth, they should recall that biology took generations to become Darwinian, and they must understand that the social sciences may take as long to become evolutionary.

Journal Article↗

Behavioral genetics and evolutionary psychology: unified perspective on personality research.

Behavioral geneticists and evolutionary psychologists have generally pursued human behavioral analyses with little theoretical or methodological exchange. However, significant benefits might accrue from increased communication between these disciplines. The primary goals of this article are (1) to identify meaningful junctures between behavioral genetics and evolutionary psychology, (2) to describe behavioral genetic research designs and their applications to evolutionary analyses, and (3) to reassess current personality research in light of behavioral genetic and evolutionary concepts and techniques. The five-factor model of personality is conceptualized as subsuming variation in normative species-typical systems with adaptive functions in the human environment of evolutionary adaptation. Considered as universal evolved mechanisms, personality systems are often seen in dynamic conflict within individuals and as highly compartmentalized in their functioning between settings. However, genetically influenced individual differences in personality may also be understood within an evolutionary framework. Studies of the heritability of personality traits indicate broad-sense heritabilities in the 0.40-0.50 range with evidence of substantial nonadditive genetic variation and nonshared environmental influences. Evidence indicates that evolutionary theory (e.g., inclusive fitness theory) predicts patterns of social interaction (e.g., cooperation and bereavement) in relatives. Furthermore, variation in personality may constitute a range of viable strategies matching the opportunities available in the complex niche environment of human societies. Within this wide range of viable strategies, personality variation functions as a resource environment for individuals in the sense that personality variation is evaluated according to the interests of the evaluator (e.g., friendships, coalitions, or mate choice).

Biological Evolution↗

Cladistic approaches to identifying determinants of variability in multifactorial phenotypes and the evolutionary significance of variation in the human genome.

Genetic surveys based on detailed restriction site mapping or DNA sequencing allow one to identify many different classes of mutational change at the molecular level and to estimate the evolutionary history of the genetic variation (a haplotype tree). These two sources of information can be combined in a powerful fashion to test hypotheses about the evolutionary significance of genetic variation and to identify mutations that are associated with diseases. Hypotheses about selection on various classes of genetic variation can be tested by examining the distribution patterns of different mutational classes upon the haplotype tree. The power of this procedure can be enhanced if it is coupled with comparative data from other, closely related species. With respect to disease associations, all mutations that affect phenotypic variation in a population occurred at some point in the evolutionary history of the region of the gene containing the mutations. Even if this evolutionary history is estimated from mutations other than those causing phenotypic effects, the phenotypically important mutations are imbedded in this same evolutionary history. Hence, whole branches (clades) of the haplotype tree should display homogeneous phenotypic effects and this fact is utilized to search for phenotypic associations of haplotypes by using nested clades in a haplotype tree. This procedure has more power than alternatives that do not use evolutionary history, and it avoids several statistical and interpretative problems associated with single-marker analyses. All of these methods could be used more extensively if more human genetic surveys concentrated on greater genetic resolution in small DNA regions and included non-human apes.

Animals↗

The mine--body problem in an evolutionary perspective.

Charles Darwin realized that his theory of evolution, jointly with the psychoneural identity hypothesis, implies the conjecture that behaviour and ideation evolve alongside anatomical and physiological traits. He was therefore the founder of evolutionary psychology. However, this science has not been pursued with vigour: not even its name has attained currency. In fact most psychologists still think in a pre-evolutionary fashion and seldom ask questions about the adaptive value and possible evolution of behavioural and mental traits. One reason for the underdevelopment of evolutionary psychology is that, on the whole, psychology is still separate from biology. In turn, one reason for this estrangement between close relatives is that psychology is still to some extent in the grip of psychoneural dualism, or the prehistoric belief that mind and body are separate entities. This doctrine is bound to block the advance of evolutionary psychology because a dualist must either deny mental evolution or speculate that it proceeds by some mechanism other than genic variation and natural (and social) selection. On the other hand the psychoneural identity hypothesis fits in with biology and, in particular, with evolutionary biology. Moreover, by construing ideation as a brain process, psychoneural monism explains how ideas (via behaviour) can become a motor of evolution as well as an outcome of it. So, it is in the interest of evolutionary psychologists to pay closer attention to the mind-body problem and to adopt the psychoneural identity hypothesis and turn it into a full-fledged scientific theory.

Animals↗

Genetic and evolutionary fitness.

The advantages and disadvantages of evolutionary fitness (probability that a single mutant line will not become extinct) and genetic fitness (mean fecundity) are compared. For deterministic processes the two are equivalent, but for stochastic branching processes they may be totally unrelated except that an absolute genetic fitness of unity or less implies an evolutionary fitness of zero. To know the variance as well as the mean family size does not in general uniquely determine the evolutionary fitness. Except where genetic fitness is close to unity, the impact of selection is shown to be rapid for the binomial, Poisson, negative binomial, and truncated negative binomial distributions. Evolutionary fitness, though somewhat cumbersome, has greater relevance to evolution, genetic counseling, and voluntary population control; but genetic fitness which is much easier to handle is the more appropriate measure where a large number of mutants is involved. Some empirical data on the transmission of various types of characters from parent to child are analyzed to allow comparison of genetic fitness, Crow's index, and a Malthusian parameter, with evolutionary fitness. There is a fair, but far from perfect, agreement among them. Multiple correlation of evolutionary fitness with mean and variance of family size taken jointly suggests a much more satisfactory approximation. It thus appears that, at the least, the population geneticist cannot afford to ignore the variance (which is not adequately represented in Crow's index). These relationships, based on two sets of data only may be accidental and should be invoked with caution. It seems more than likely that other aspects of the distribution of family size (eg, even higher moments) may contain relevant information in certain cases.

Biological Evolution↗

Kowalevsky, comparative evolutionary embryology, and the intellectual lineage of evo-devo.

Alexander Kowalevsky was one of the most significant 19th century biologists working at the intersection of evolution and embryology. The reinstatement of the Alexander Kowalevsky Medal by the St. Petersburg Society of Naturalists for outstanding contributions to understanding evolutionary relationships in the animal kingdom, evolutionary developmental biology, and comparative zoology is timely now that Evo-devo has emerged as a major research discipline in contemporary biology. Consideration of the intellectual lineage of comparative evolutionary embryology explicitly forces a reconsideration of some current conceptions of the modern emergence of Evo-devo, which has tended to exist in the shadow of experimental embryology throughout the 20th century, especially with respect to the recent success of developmental biology and developmental genetics. In particular we advocate a sharper distinction between the heritage of problems and the heritage of tools for contemporary Evo-devo. We provide brief overviews of the work of N. J. Berrill and D. T. Anderson to illustrate comparative evolutionary embryology in the 20th century, which provides an appropriate contextualization for a conceptual review of our research on the sea urchin genus Heliocidaris over the past two decades. We conclude that keeping research questions rather than experimental capabilities at the forefront of Evo-devo may be an antidote to any repeat of the stagnation experienced by the first group of evolutionary developmental biologists over one hundred years ago and acknowledges Kowalevsky's legacy in evolutionary embryology.

Animals↗

Combining evolutionary and structural information for local protein structure prediction.

We study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non-redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position-specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS-type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile-profile comparison. We show that the COMPASS-type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side-chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log-odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log-odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile-to-profile alignment by COMPASS.

Algorithms↗

Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota.

The evolutionary origin of "orphan" genes, genes that lack sequence similarity to any known gene, remains a mystery. One suggestion has been that most orphan genes evolve rapidly so that similarity to other genes cannot be traced after a certain evolutionary distance. This can be tested by examining the divergence rates of genes with different degrees of lineage specificity. Here the lineage specificity (LS) of a gene describes the phylogenetic distribution of that gene's orthologues in related species. Highly lineage-specific genes will be distributed in fewer species in a phylogeny. In this study, we have used the complete genomes of seven ascomycotan fungi and two animals to define several levels of LS, such as Eukaryotes-core, Ascomycota-core, Euascomycetes-specific, Hemiascomycetes-specific, Aspergillus-specific, and Saccharomyces-specific. We compare the rates of gene evolution in groups of higher LS to those in groups with lower LS. Molecular evolutionary analyses indicate an increase in nonsynonymous nucleotide substitution rates in genes with higher LS. Several analyses suggest that LS is correlated with the evolutionary rate of the gene. This correlation is stronger than those of a number of other factors that have been proposed as predictors of a gene's evolutionary rate, including the expression level of genes, gene essentiality or dispensability, and the number of protein-protein interactions. The accelerated evolutionary rates of genes with higher LS may reflect the influence of selection and adaptive divergence during the emergence of orphan genes. These analyses suggest that accelerated rates of gene evolution may be responsible for the emergence of apparently orphan genes.

Ascomycota↗

Remarks on branching-extinction evolutionary cycles.

We show in this paper that the evolution of cannibalistic consumer populations can be a never ending story involving alternating levels of polymorphism. More precisely, we show that a monomorphic population can evolve toward high levels of cannibalism until it reaches a so-called branching point, where the population splits into two sub-populations characterized by different, but initially very close, cannibalistic traits. Then, the two traits coevolve until the more cannibalistic sub-population undergoes evolutionary extinction. Finally, the remaining population evolves back to the branching point, thus closing an evolutionary cycle. The model on which the study is based is purely deterministic and derived through the adaptive dynamics approach. Evolutionary dynamics are investigated through numerical bifurcation analysis, applied both to the ecological (resident-mutant) model and to the evolutionary model. The general conclusion emerging from this study is that branching-extinction evolutionary cycles can be present in wide ranges of environmental and demographic parameters, so that their detection is of crucial importance when studying evolutionary dynamics.

Adaptation, Physiological↗

Evolutionary suicide and evolution of dispersal in structured metapopulations.

We study the evolution of dispersal in a structured metapopulation model. The metapopulation consists of a large (infinite) number of local populations living in patches of habitable environment. Dispersal between patches is modelled by a disperser pool and individuals in transit between patches are exposed to a risk of mortality. Occasionally, local catastrophes eradicate a local population: all individuals in the affected patch die, yet the patch remains habitable. We prove that, in the absence of catastrophes, the strategy not to migrate is evolutionarily stable. Under a given set of environmental conditions, a metapopulation may be viable and yet selection may favor dispersal rates that drive the metapopulation to extinction. This phenomenon is known as evolutionary suicide. We show that in our model evolutionary suicide can occur for catastrophe rates that increase with decreasing local population size. Evolutionary suicide can also happen for constant catastrophe rates, if local growth within patches shows an Allee effect. We study the evolutionary bifurcation towards evolutionary suicide and show that a discontinuous transition to extinction is a necessary condition for evolutionary suicide to occur. In other words, if population size smoothly approaches zero at a boundary of viability in parameter space, this boundary is evolutionarily repelling and no suicide can occur.

Adaptation, Biological↗

The descent of words: evolutionary thinking 1780-1880.

Histories of evolutionary thought are dominated by organic evolution. The colossus in our midst that is evolutionary biology casts its shadow over history, making it appear that what is so widespread and important today was always the primary subject of evolutionary speculation. Thus many histories assume that the core meaning of evolution is the change of organic life and that other forms of evolutionary thinking, such as linguistic, social or cultural evolution, are only analogies or offshoots of the main biological evolutionary trunk. Ironically this is an ahistorical understanding. Long before the work of Charles Darwin, scholars were independently developing evolutionary concepts such as descent with modification and divergence from a common stock in order to understand cultural change.

Biological Evolution↗

Differential evolutionary rates of duplicated genes in protein interaction network.

In the network of protein-protein interactions (PPIs), a loss and gain of the partnering proteins can cause drastic changes of network formation during evolution. With the aim of examining the evolutionary effects of the loss and gain of the partnering proteins on PPIs, we examined a relationship between evolutionary rates and losses and/or gains of PPIs for duplicated gene pairs encoding proteins involved in the PPI network. For duplicated pairs, which provided us with a unique opportunity of making fair comparisons of the genes with the same initial condition, we found that the evolutionary rate of the protein with more PPI partners is much slower than that of the other with fewer PPI partners. Moreover, when the ratio of evolutionary rates (faster rate/slower rate) was computed for each of the duplicated pairs, the ratio for the duplicated pair sharing any PPI partners was significantly lower than that for the pair sharing no PPI partners. These results indicate that the duplicated gene pairs differentiate through the losses and/or gains of the PPI partners, resulting in a change in their evolutionary rates. In particular, we point out that the PPI losses for the duplicated gene products that are involved in the functional classes of 'transcription' and 'protein fate' have an impact on their evolutionary rates more than the PPI losses for others.

Biological Evolution↗

Correlated evolutionary pressure at interacting transcription factors and DNA response elements can guide the rational engineering of DNA binding specificity.

Understanding the molecular mechanisms of the specific interaction between transcription factor proteins and DNA is key to comprehend the regulation of gene expression and to develop technologies to engineer transcription factors. Thus far, although there have been several attempts to elucidate protein-DNA interaction through amino acid-base recognition codes, sequence based profiles, or physical models of interaction, the greatest successes in engineering DNA binding specificity remain experimental. Here we present the first systematic evidence of correlated evolutionary pressure at interacting amino acid residues and DNA base-pairs in transcription factors, and show that it can be used to rationally engineer DNA binding specificity. The correlation is between the relative evolutionary importance of protein residues and DNA bases, measured, respectively, in terms of the Evolutionary Trace (ET) rank and information entropy. The evolutionarily most important residues interact with the most conserved base-pairs within the response element while residues of least importance interact with the most variable base-pairs. The correlation averages 0.74 over 12 unrelated families of transcriptional regulators, including nuclear hormone receptors, basic helix-loop-helix, ETS- and homeo-domain family. To test the predictive power of this correlation, we targeted a mutational swap of top-ranked ET residues in a transcription factor, LRH-1. This redirects LRH-1 binding as predicted and showed that, in this case, evolutionary importance and binding specificity are coupled sufficiently strongly for the Evolutionary Trace to guide the computational design of DNA binding specificity. This establishes the existence of evolutionary importance correlation at protein-DNA interfaces, and demonstrates that it is a useful principle for the rational engineering of binding specificity.

Animals↗

Inferring functional linkages between proteins from evolutionary scenarios.

Identifying potential protein interactions is of great importance in understanding the topologies of cellular networks, which is much needed and valued in current systematic biological studies. The development of our computational methods to predict protein-protein interactions have been spurred on by the massive sequencing efforts of the genomic revolution. Among these methods is phylogenetic profiling, which assumes that proteins under similar evolutionary pressures with similar phylogenetic profiles might be functionally related. Here, we introduce a method for inferring functional linkages between proteins from their evolutionary scenarios. The term evolutionary scenario refers to a series of events that occurred in speciation over time, which can be reconstructed given a phylogenetic profile and a species tree. Common evolutionary pressures on two proteins can then be inferred by comparing their evolutionary scenarios, which is a direct indication of their functional linkage. This scenario method has proven to have better performance compared with the classical phylogenetic profile method, when applied to the same test set. In addition, predicted results of the two methods are found to be fairly different, suggesting the possibility of merging them in order to achieve a better performance. We analyzed the influence of the topology of the phylogenetic tree on the performance of this method, and found it to be robust to perturbations in the topology of the tree. However, if a completely random tree is incorporated, performance will decline significantly. The evolutionary scenario method was used for inferring functional linkages in 67 species, and 40,006 linkages were predicted. We examine our prediction for budding yeast and find that almost all predicted linkages are supported by further evidence.

Computational Biology↗

Food-web formation with recursive evolutionary branching.

A reaction-diffusion model describing the evolutionary dynamics of a food-web was constructed. In this model, predator-prey relationships among organisms were determined by their position in a two-dimensional phenotype space defined by two traits: as prey and as predator. The mutation process is expressed with a diffusion process of biomass in the phenotype space. Numerical simulation of this model showed co-evolutionary dynamics of isolated phenotypic clusters, including various types of evolutionary branching, which were classified into branching as prey, branching as predators, and co-evolutionary branching of both prey and predators. A complex food-web develops with recursive evolutionary branching from a single phenotypic cluster. Biodiversity peaks at the medium strength of the predator-prey interaction, where the food-web is maintained at medium biomass by a balanced frequency between evolutionary branching and extinction.

Animals↗

Neoplastic growth: the consequence of evolutionary malignant resistance to chronic damage for survival of cells (review of a new theory of the origin of cancer).

In the present review, a new theory that the mechanisms of general evolutionary persistent resistance to damaging factors are closely related to the development of tumour cells is introduced. Evolutionary resistance and its variability have an immense power to drive and control the process of carcinogenesis and the success of microbial and antitumour chemotherapy. First, this phenomenon of adaptation is characteristic of microbial cells whose resistance to antibiotics and other chemotherapeutic drugs is manifested through ATP-dependent transmembrane transporters. The structure and function of some multidrug transporters of resistance are conserved from microorganisms to mammals. When somatic cells are exposed to carcinogens and develop into tumour cells, they also acquire resistance to the toxic effects of carcinogens through these same transmembrane transporters (P-glycoprotein, glutathione S-transferases and other products of evolutionary resistance-related genes arisen for detoxification and exportation of cytotoxic xenobiotics and drugs). Cancerous cells acquire a persistent evolutionary resistance to chemotherapy drugs or irradiation through the same ATP-dependent transporters encountered in prokaryotic and eukaryotic cells. The mechanism of acquired resistance of cells to damaging factors, which becomes manifested during tumorigenic process formation, is a general biological law of primary significance in carcinogenesis. This resistance can be called malignant as, once formed, it does not disappear, as does also a clone of malignant cells. In tumorous cells, the mutagenic processes, morphological and functional modifications are a mechanism of secondary significance in carcinogenesis, contributing to formation of damage-resistant cells. This mechanism characterizes the processes of simplification arising in damage-resistant cells. Such cells acquire parasitic features. To survive under unfavourable conditions, they get adapted as if returning down the evolutionary stairs back to a more primitive stage of atavistic regression, which is characteristic of primitive forms of existence. Therefore they cease obeying the growth-regulating mechanisms in the organism and acquire the potential of unlimited division and accelerated growth (metastases) as do unicellular organisms or their forms resistant to damaging factors in the environment and in the host organism. Thus, cancer is a natural self-protective response of the damaged cells to the biological, physical and chemical damage and oxidative stress. This response has been developed in the process of evolution under the impact of the general biological Darwinian law of nature--to survive through variability and adaptation to the changed environmental conditions. Thus, malignization is the consequence of an evolutionary variety of the general biological resistance of cells to damage and stress in order to survive.

Biological Evolution↗

Sex differences in OCD symptomatology: an evolutionary perspective.

Some evolutionists have construed obsessive-compulsive disorder (OCD) as the over-activation of warning systems in areas of evolutionary import. Using evolutionary theorizing, it is posited here that sex differences in the instantiation of specific obsessions and/or compulsions might correspond to sex-specific differences in the evolutionary import of the domain to which the particular symptom maps onto (e.g., mating versus parenting). Even in instances where no sex differences are found in the incidence of a particular obsession and/or compulsion (e.g., the extent to which men and women might suffer from intrusive thoughts), an evolutionary perspective might nonetheless propose that the contents of such thoughts map onto sex-specific adaptive concerns (e.g., social status and appearance-related concerns for men and women, respectively). An evolutionary approach might help not only in explaining sex differences in OCD phenomenology but also in elucidating within-sex manifestations of OCD symptoms (e.g., the shifting strength of contamination fears across a woman's menstrual cycle). The current evolutionary perspective not only provides an integrative ultimate-level meta-framework in understanding previously-found sex differences in OCD but also it permits OCD researchers to propose innovative hypotheses that otherwise might have been unlikely to be posited if one were to strictly focus on a proximate exploration of OCD. Cross-cultural clinical data, originating from a heterogeneous set of cultures and highlighting universal patterns of sex-specific OCD symptomatology, would provide a strong test of the posited hypotheses.

Biological Evolution↗