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Evolutionary computational methods to predict oral bioavailability QSPRs.

This review discusses evolutionary and adaptive methods for predicting oral bioavailability (OB) from chemical structure. Genetic Programming (GP), a specific form of evolutionary computing, is compared with some other advanced computational methods for OB prediction. The results show that classifying drugs into 'high' and 'low' OB classes on the basis of their structure alone is solvable, and initial models are already producing output that would be useful for pharmaceutical research. The results also suggest that quantitative prediction of OB will be tractable. Critical aspects of the solution will involve the use of techniques that can: (i) handle problems with a very large number of variables (high dimensionality); (ii) cope with 'noisy' data; and (iii) implement binary choices to sub-classify molecules with behavior that are qualitatively different. Detailed quantitative predictions will emerge from more refined models that are hybrids derived from mechanistic models of the biology of oral absorption and the power of advanced computing techniques to predict the behavior of the components of those models in silico.

Animals↗

Detecting adaptive trait introgression between Iris fulva and I. brevicaulis in highly selective field conditions.

The idea that natural hybridization has served as an important force in evolutionary and adaptive diversification has gained considerable momentum in recent years. By combining genome analyses with a highly selective field experiment, we provide evidence for adaptive trait introgression between two naturally hybridizing Louisiana Iris species, flood-tolerant Iris fulva and dry-adapted I. brevicaulis. We planted reciprocal backcross (BC1) hybrids along with pure-species plants into natural settings that, due to a flooding event, favored I. fulva. As expected, I. fulva plants survived at much higher rates than I. brevicaulis plants. Backcross hybrids toward I. fulva (BCIF) also survived at significantly higher rates than the reciprocal backcross toward I. brevicaulis (BCIB). Survivorship of BCIB hybrids was strongly influenced by the presence of a number of introgressed I. fulva alleles located throughout the genome, while survivorship in the reciprocal BCIF hybrids was heavily influenced by two epistatically acting QTL of opposite effects. These results demonstrate the potential for adaptive trait introgression between these two species and may help to explain patterns of genetic variation observed in naturally occurring hybrid zones.

Chimera↗

Bayesian estimation of the timing and severity of a population bottleneck from ancient DNA.

In this first application of the approximate Bayesian computation approach using the serial coalescent, we demonstrated the estimation of historical demographic parameters from ancient DNA. We estimated the timing and severity of a population bottleneck in an endemic subterranean rodent, Ctenomys sociabilis, over the last 10,000 y from two cave sites in northern Patagonia, Argentina. Understanding population bottlenecks is important in both conservation and evolutionary biology. Conservation implications include the maintenance of genetic variation, inbreeding, fixation of mildly deleterious alleles, and loss of adaptive potential. Evolutionary processes are impacted because of the influence of small populations in founder effects and speciation. We found a decrease from a female effective population size of 95,231 to less than 300 females at 2,890 y before present: a 99.7% decline. Our study demonstrates the persistence of a species depauperate in genetic diversity for at least 2,000 y and has implications for modes of speciation in the incredibly diverse rodent genus Ctenomys. Our approach shows promise for determining demographic parameters for other species with ancient and historic samples and demonstrates the power of such an approach using ancient DNA.

Animals↗

Rapid phenotypic change and diversification of a soil bacterium during 1000 generations of experimental evolution.

Evolutionary pathways open to even relatively simple organisms, such as bacteria, may lead to complex and unpredictable phenotypic changes, both adaptive and non-adaptive. The evolutionary pathways taken by 18 populations of Ralstonia strain TFD41 while they evolved in defined environments for 1000 generations were examined. Twelve populations evolved in liquid media, while six others evolved on agar surfaces. Phenotypic analyses of these derived populations identified some changes that were consistent across all populations and others that differed among them. The evolved populations all exhibited morphological changes in their cell envelopes, including reductions of the capsule in each population and reduced prostheca-like surface structures in most populations. Mean cell length increased in most populations (in one case by more than fourfold), although a few populations evolved shorter cells. Carbon utilization profiles were variable among the evolved populations, but two distinct patterns were correlated with genetic markers introduced at the outset of the experiment. Fatty acid methyl ester composition was less variable across populations, but distinct patterns were correlated with the two physical environments. All 18 populations evolved greatly increased sensitivity to bile salts, and all but one had increased adhesion to sand; both patterns consistent with changes in the outer envelope. This phenotypic diversity contrasts with the fairly uniform increases in competitive fitness observed in all populations. This diversity may represent a set of equally probable adaptive solutions to the selective environment; it may also arise from the chance fixation of non-adaptive mutations that hitchhiked with a more limited set of beneficial mutations.

Bacterial Adhesion↗

Mitochondrial mechanisms of cold adaptation in cod (Gadus morhua L.) populations from different climatic zones.

Adjustments in mitochondrial properties and capacities are crucial in acclimatization to seasonal cold as well as in evolutionary cold adaptation of marine ectotherms. To examine whether gene expression mechanisms contribute to different settings of aerobic capacities in populations of cod (Gadus morhua) along a latitudinal cline, maximum activities of key enzymes of mitochondrial metabolism and their respective mRNA levels were compared in white muscle and liver of cold (4 degrees C) and warm (10 degrees C) acclimated individuals from cod populations of the North Sea and the Barents Sea, respectively. In white muscle, cold acclimation caused a parallel increase in citrate synthase (CS) and in cytochrome c oxidase (COX) activities, but with a much larger effect in the cold eurythermal Arctic population. In liver, cold acclimation was accompanied by increments in CS activities, but differences between populations were minor. Overall COX activities in liver were not affected by cold acclimation, but were higher in the cold adapted population. In both populations increments in muscle CS capacities were tightly correlated with elevated mRNA levels, suggesting transcriptional control of citrate synthase levels in muscle. In liver, CS mRNA levels differed between populations but were not affected by cold acclimation, so that post-transcriptional control may contribute to elevated functional levels in this tissue. Mitochondrial-encoded COX2 mRNA levels were not limiting for functional activities in both tissues, in favour of post-transcriptional control or limitations by other transcripts of the COX complex. Altogether, the differentiation in gene expression between both populations was more strongly expressed at 4 degrees C. The comparison of functional levels and transcript levels may reflect genetic differentiation at functional sites, in line with genetic differences between the two populations previously established by non-coding genetic markers.

Acclimatization↗

High altitude adaptation in Tibetans.

Since the beginning of the Himalayan climbing era, the anecdotal extraordinary physical performance at high altitude of Sherpas and Tibetans has intrigued scientists interested in altitude adaptation. These ethnic groups may have been living at high altitude for longer than any other population, and the hypothesis of a possible evolutionary genetic adaptation to altitude makes sense. Reviewed here is the evidence as to whether Tibetans are indeed better adapted for life and work at high altitude as compared to other populations and, if so, whether this better adaptation might be inborn. Tibetans, compared to lowlanders, maintain higher arterial oxygen saturation at rest and during exercise and show less loss of aerobic performance with increasing altitude. Tibetans have greater hypoxic and hypercapnic ventilatory responsiveness, larger lungs, better lung function, and greater lung diffusing capacity than lowlanders. Blood hemoglobin concentration is lower in Tibetans than in lowlanders or Andeans living at similar altitudes. Tibetans develop only minimal hypoxic pulmonary hypertension and have higher levels of exhaled nitric oxide than lowlanders or Andeans. Tibetans' sleep quality at altitude is better and they desaturate less at night. Several of these findings are also found in Tibetans born at low altitude when exposed for the first time to high altitude once adult. In conclusion, Tibetans indeed seem better adapted to life and work at high altitude, and this superior adaptation may very well be inborn, even though its exact genetic basis remains to be elucidated.

Acclimatization↗

An evolutionary perspective of endotoxin: a signal for a well-adapted defense system.

In the evolutionary view of endotoxin presented here, endotoxin is the primary signal animals use to detect gram negative (Gr-) bacteria. Since endotoxin, or lipopolysaccharide (LPS), is an integral part of the surface of all Gr- bacteria, it was excellent evolutionary 'choice' for the signal. The concept of an 'endotoxin response system' (ERS) is introduced. The ERS protects against Gr- bacteria by employing many of the body's defenses to both detect and react against LPS. The intensity of the response has evolved to maximize protection while minimizing the biological cost and self-damaging effects. The setting of the response, here termed the 'endostat', is programmed by natural selection and fine tuned by feedback mechanisms. Other potentially invasive organisms are detected by different signals, but the effector components of the defenses are similar. This evolutionary view of LPS offers a framework for the seemingly contradictory findings on endotoxin and suggests new avenues of productive research.

Adaptation, Physiological↗

Evolution in Hawaiian cave-adapted isopods (Oniscidea: Philosciidae): vicariant speciation or adaptive shifts?

We assessed evolutionary relationships among Hawaiian cave-adapted isopods using a maximum-likelihood criterion to analyze cytochrome oxidase I nucleotide sequences. Results support morphological data that two genera of philosciid isopods have invaded caves independently in the islands. In the genus Littorophiloscia, a sister relationship between a surface-dwelling species, L. hawaiiensis, and an undescribed cave species was corroborated. This evidence, along with the known parapatric distributions between species, supports a speciation event by an adaptive shift on the island of Hawaii from a marine littoral to a terrestrial subterranean habitat. The monophyletic genus Hawaiioscia contains four known obligate cave-dwelling species, each of which occurs on a separate island. However, despite present-day allopatric distributions between Hawaiioscia species, the geographic and phylogenetic patterns are not sufficient to support a vicariant mode of speciation. Instead, we believe that the known species of Hawaiioscia evolved from a widespread ancestral surface species or a group of closely related species through multiple, independent adaptive shifts on each of the islands of Kauai, Oahu, Molokai, and Maui. This is the first molecular investigation of evolutionary relationships between surface-dwelling and cavernicolous arthropods in Hawaii and it suggests that simple vicariance is insufficient to explain the evolution of troglobites in tropical zones.

Adaptation, Physiological↗

How well are bones designed to resist fracture?

Because bone is obviously in some way adapted to the loads falling on it and because fracture is usually the failure of mechanical competence of main clinical importance, it is often thought that bones are adapted to resist fracture. In this perspective, I consider that this may not be the case. Bones may be designed to be very stiff, and therefore highly mineralized, and therefore brittle; they may be adapted to normal loads, but not to the characteristic loads occurring in falls, or may be very poorly designed to stop cracks traveling once they have started. Bones may also potentially fail in completely contrasting modes, and therefore their design has to be a compromise that does not resist either mode completely successfully. The greatly differing fracture incidences in different bones seen in pre-senile adults suggest that safety factors have been adapted, over evolutionary time, to produce the best compromise for a host of different design constraints.

Adaptation, Physiological↗

Hormesis: a generalizable and unifying hypothesis.

The present article represents a comprehensive effort to assess the hypothesis that hormesis is a highly generalizable biological phenomenon independent of environmental stressor, biological endpoint, and experimental model system. The evaluative methodology and complementary approaches employed to assess this question are (1) evolutionary biology-based theoretical paradigm; (2) evaluation of > 20,000 toxicology articles using a priori entry and evaluative criteria; (3) evaluation of 17 large-scale studies each providing data on numerous agents tested in the same experimental model by the same research team; (4) the assimilation of experimental pharmacological data on 24 receptor systems in which biphasic dose responses have been established reproducibly along with hormetic mechanism elucidation; and (5) assessment of the original hormesis database with 1600 dose-response relationships demonstrating evidence consistent with the hormesis hypothesis. The complementary approaches for assessing hormesis provided strong support for its credibility as a central biological theory based on its high frequency of occurrence and quantitative features of expression within microbe, plant, and invertebrate and vertebrate animal systems. The findings suggest that hormetic effects represent evolutionary-based adaptive responses to environmentally induced disruptions in homeostasis. Such adaptive responses, which are incorporated into organismal integrative physiological systems and now clarified at the mechanistic level for more than two dozen receptor systems, provide a cogent basis for the application of hormetic mechanisms in the elucidation of fundamental evolutionary-based biological processes and in the development of novel clinical modalities.

Adaptation, Physiological↗

Information and its use by animals in evolutionary ecology.

Information is a crucial currency for animals from both a behavioural and evolutionary perspective. Adaptive behaviour relies upon accurate estimation of relevant ecological parameters; the better informed an individual, the better it can develop and adjust its behaviour to meet the demands of a variable world. Here, we focus on the burgeoning interest in the impact of ecological uncertainty on adaptation, and the means by which it can be reduced by gathering information, from both 'passive' and 'responsive' sources. Our overview demonstrates the value of adopting an explicitly informational approach, and highlights the components that one needs to develop useful approaches to studying information use by animals. We propose a quantitative framework, based on statistical decision theory, for analysing animal information use in evolutionary ecology. Our purpose is to promote an integrative approach to studying information use by animals, which is itself integral to adaptive animal behaviour and organismal biology.

Journal Article↗

Intrinsic noise and the design of the genetic machinery.

Darwinian theory envisages 'selection pressure' as a stress imposed on the genotype by the environment. However, noise in the replicative and translational mechanisms in itself imposes a significant 'pressure' on the adaptive fitness of the organism. We propose that the biosphere has been shaped by both extrinsic (environmental) and intrinsic (noise-generated) factors. Because noise has been a remorseless and ever-present background to the evolutionary process, adaptations to this intrinsic pressure include not only a variety of familiar genetic mechanisms but also many anatomical and life-style characteristics that focus on the transmission of information between generations.

Animals↗

Hidden Diversity in the Sands: Genomic Footprints of Pleistocene Refugia and Fragile Futures of the Turkestan Ground-Jay (Podoces panderi) in Central Asia.

The Turkestan ground-jay (Podoces panderi), a corvid endemic to Central Asia's deserts and steppes, exemplifies how extreme environments drive speciation. Our study provides the first comprehensive high-resolution genomic analysis of this species, using complete mitochondrial genomes (49 individuals) to decode its population structure and demographic past. Our analyses revealed three highly divergent genetic clusters with strong geographic structure. The P. p. iliensis population (Cluster_3) showed particularly pronounced genetic distinctiveness, with significant differentiation from P. p. panderi (Cluster_2 and Cluster_1) populations. This clear genetic separation supports the taxonomic validity of P. p. iliensis as a distinct evolutionary lineage. Demographic reconstruction indicated that Cluster_2 likely represents the ancestral group, with subsequent southward expansion into the Karakum region. The isolated P. p. iliensis population exhibited signatures of long-term isolation, including reduced genetic diversity and absence of recent gene flow with other clusters. These results provide strong evidence that P. p. iliensis represents a distinct evolutionary unit. The genetic structuring into three clusters reflects historical isolation in desert refugia during Pleistocene climatic fluctuations. Notably, we detected asymmetric gene flow among three clusters. These findings redefine P. panderi as a model for desert adaptation, where climatic extremes forged genetic fragmentation amid limited dispersal. Beyond taxonomy, our work highlights how aridification sculpted biodiversity in Asia's interior, urging conservation attention for these evolutionarily distinct lineages.

Animals↗

Mutation-based genetic neural network.

Evolving gradient-learning artificial neural networks (ANNs) using an evolutionary algorithm (EA) is a popular approach to address the local optima and design problems of ANN. The typical approach is to combine the strength of backpropagation (BP) in weight learning and EA's capability of searching the architecture space. However, the BP's "gradient descent" approach requires a highly computer-intensive operation that relatively restricts the search coverage of EA by compelling it to use a small population size. To address this problem, we utilized mutation-based genetic neural network (MGNN) to replace BP by using the mutation strategy of local adaptation of evolutionary programming (EP) to effect weight learning. The MGNN's mutation enables the network to dynamically evolve its structure and adapt its weights at the same time. Moreover, MGNN's EP-based encoding scheme allows for a flexible and less restricted formulation of the fitness function and makes fitness computation fast and efficient. This makes it feasible to use larger population sizes and allows MGNN to have a relatively wide search coverage of the architecture space. MGNN implements a stopping criterion where overfitness occurrences are monitored through "sliding-windows" to avoid premature learning and overlearning. Statistical analysis of its performance to some well-known classification problems demonstrate its good generalization capability. It also reveals that locally adapting or scheduling the strategy parameters embedded in each individual network may provide a proper balance between the local and global searching capabilities of MGNN.

Algorithms↗

Robustness and evolution: concepts, insights and challenges from a developmental model system.

Robustness, the persistence of an organismal trait under perturbations, is a ubiquitous property of complex living systems. We here discuss key concepts related to robustness with examples from vulva development in the nematode Caenorhabditis elegans. We emphasize the need to be clear about the perturbations a trait is (or is not) robust to. We discuss two prominent mechanistic causes of robustness, namely redundancy and distributed robustness. We also discuss possible evolutionary causes of robustness, one of which does not involve natural selection. To better understand robustness is of paramount importance for understanding organismal evolution. Part of the reason is that highly robust systems can accumulate cryptic variation that can serve as a source of new adaptations and evolutionary innovations. We point to some key challenges in improving our understanding of robustness.

Animals↗

Unifying evolutionary dynamics.

Darwinian evolution is based on three fundamental principles, reproduction, mutation and selection, which describe how populations change over time and how new forms evolve out of old ones. There are numerous mathematical descriptions of the resulting evolutionary dynamics. In this paper, we show that apparently very different formulations are part of a single unified framework. At the center of this framework is the equivalence between the replicator-mutator equation and the Price equation. From these equations, we obtain as special cases adaptive dynamics, evolutionary game dynamics, the Lotka-Volterra equation of ecology and the quasispecies equation of molecular evolution.

Animals↗

Is ADHD adaptive or non-adaptive behavior?

The evolutionary approach to the issue of ADHD derives from the assumption that what is regarded as a pathological phenomenon today was once an adaptive response to the conditions of life in the ancestral stages of human development. The paper argues against this conception on the basis of the clinical picture of ADHD. The author believes that in the previous "natural" conditions the ADHD syndrome was even more of a maladaptation than in the "protective" conditions of present-day life.

Adaptation, Psychological↗

Neutral adaptation of the genetic code to double-strand coding.

We lay new foundations to the hypothesis that the genetic code is adapted to evolutionary retention of information in the antisense strands of natural DNA/RNA sequences. In particular, we show that the genetic code exhibits, beyond the neutral replacement patterns of amino acid substitutions, optimal properties by favoring simultaneous evolution of proteins encoded in DNA/RNA sense-antisense strands. This is borne out in the sense-antisense transformations of the codons of every amino acid which target amino acids physicochemically similar to each other. Moreover, silent mutations in the sense strand generate conservative ones in its antisense counterpart and vice versa. Coevolution of proteins coded by complementary strands is shown to be a definite possibility, a result which does not depend on any physical interaction between the coevolving proteins. Likewise, the degree to which the present genetic code is dedicated to evolutionary sense-antisense tolerance is demonstrated by comparison with many randomized codes. Double-strand coding is quantified from an information-theoretical point of view.

Adaptation, Biological↗