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Ontogenies in mice selected for high voluntary wheel-running activity. I. Mean ontogenies.

The evolutionary importance of postnatal ontogenies has long been recognized, but most studies of ontogenetic trajectories have focused exclusively on morphological traits. For animals, this represents a major omission because behavioral traits and their ontogenies often have relatively direct relationships to fitness. Here four replicate lines of house mice artificially selected for high early-age wheel running and their four replicate control lines were used to evaluate the effects of early-age directional selection, genetic drift, and activity environment (presence or absence of a running wheel) on variation in the ontogenies of three traits known to be genetically correlated: voluntary wheel running, body mass, and food consumption. Early-age selection significantly changed both the shape and position of the wheel-running and food-consumption ontogenies while influencing the position, but not the shape, of the body mass ontogeny. Genetic drift (as indicated by variation among replicate lines) produced significant changes in both the position and shape of all three ontogenies; however, its effect differed between the selection and control groups. For wheel running and food consumption, genetic drift only influenced the control ontogenies, whereas for body mass, genetic drift had a significant effect in both selection groups. Both body-mass and food-consumption ontogenies were significantly altered by activity environment, with the environment causing significant changes in the shape and position of both ontogenies. Overall the results demonstrate strong effects of early-age selection, genetic drift, and environmental variation on the evolution and expression of behavioral and morphological ontogenies, with selection changing only the position of the morphological ontogeny but both the position and shape of the behavioral ontogenies.

Analysis of Variance↗

Longevity and ageing: appraising the evolutionary consequences of growing old.

Senescence or ageing is an increase in mortality and/or decline in fertility with increasing age. Evolutionary theories predict that ageing or longevity evolves in response to patterns of extrinsic mortality or intrinsic damage. If ageing is viewed as the outcome of the processes of behaviour, growth and reproduction then it should be possible to predict mortality rate. Recent developments have shown that it is now possible to integrate these ecological and physiological processes and predict the shape of mortality trajectories. By drawing on the key exciting developments in the cellular, physiological and ecological process of longevity the evolutionary consequences of ageing are reviewed. In presenting these ideas an evolutionary demographic framework is used to argue how trade-offs in life-history strategies are important in the maintenance of variation in longevity within and between species. Evolutionary processes associated with longevity have an important role in explaining levels of biological diversity and speciation. In particular, the effects of life-history trait trade-offs in maintaining and promoting species diversity are explored. Such trade-offs can alleviate the effects of intense competition between species and promote species coexistence and diversification. These results have important implications for understanding a number of core ecological processes such as how species are divided among niches, how closely related species co-occur and the rules by which species assemble into food-webs. Theoretical work reveals that the proximate physiological processes are as important as the ecological factors in explaining the variation in the evolution of longevity. Possible future research challenges integrating work on the evolution and mechanisms of growing old are briefly discussed.

Aging↗

Under cover: causes, effects and implications of Hsp90-mediated genetic capacitance.

The environmentally responsive molecular chaperone Hsp90 assists the maturation of many key regulatory proteins. An unexpected consequence of this essential biochemical function is that genetic variation can accumulate in genomes and can remain phenotypically silent until Hsp90 function is challenged. Notably, this variation can be revealed by modest environmental change, establishing an environmentally responsive exposure mechanism. The existence of diverse cryptic polymorphisms with a plausible exposure mechanism in evolutionarily distant lineages has implications for the pace and nature of evolutionary change. Chaperone-mediated storage and release of genetic variation is undoubtedly rooted in protein-folding phenomena. As we discuss, proper protein folding crucially affects the trajectory from genotype to phenotype. Indeed, the impact of protein quality-control mechanisms and other fundamental cellular processes on evolution has heretofore been overlooked. A true understanding of evolutionary processes will require an integration of current evolutionary paradigms with the many new insights accruing in protein science.

Animals↗

An experimental manipulation of life-history trajectories and resistance to oxidative stress.

Optimal investment into life-history traits depends on the environmental conditions that organisms are likely to experience during their life. Evolutionary theory tells us that optimal investment in reproduction versus maintenance is likely to shape the pattern of age-associated decline in performance, also known as aging. The currency that is traded against different vital functions is, however, still debated. Here, we took advantage of a phenotypic manipulation of individual quality in early life to explore (1) long-term consequences on life-history trajectories, and (2) the possible physiological mechanism underlying the life-history adjustments. We manipulated phenotypic quality of a cohort of captive zebra finches (Taeniopygia guttata) by assigning breeding pairs to either an enlarged or a reduced brood. Nestlings raised in enlarged broods were in poorer condition than nestlings raised in reduced broods. Interestingly, the effect of environmental conditions experienced during early life extended to the age at first reproduction. Birds from enlarged broods delayed reproduction. Birds that delayed reproduction produced less offspring but lived longer, although neither fecundity nor longevity were directly affected by the experimental brood size. Using the framework of the life-table response experiment modeling, we also explored the effect of early environmental condition on population growth rate and aging. Birds raised in reduced broods tended to have a higher population growth rate, and a steeper decrease of reproductive value with age than birds reared in enlarged broods. Metabolic resources necessary to fight off the damaging effect of reactive oxygen species (ROS) could be the mechanism underlying the observed results, as (1) birds that engaged in a higher number of breeding events had a weaker red blood cell resistance to oxidative stress, (2) red blood cell resistance to oxidative stress predicted short-term mortality (but not longevity), and (3) was related with a parabolic function to age. Overall, these results highlight that early condition can have long-term effects on life-history trajectories by affecting key life-history traits such as age at first reproduction, and suggest that the trade-off between reproduction and self-maintenance might be mediated by the cumulative deleterious effect of ROS.

Aging↗

Whole-organism studies of adhesion in pad-bearing lizards: creative evolutionary solutions to functional problems.

Understanding the evolution of complex functional traits is a challenge for evolutionary physiology. Here we investigate the evolution of subdigital toepads in lizards, which have arisen independently at least three times, although with subtle anatomical differences. Some designs (anole, gecko) appear functionally equivalent, whereas other designs (skink) are inferior. The functional equivalence of geckos and anoles highlights the creative aspect of the evolutionary process in that these two groups have arrived at the same functional endpoint along very different trajectories. However, this functional equivalence does not result in equivalence for performance at whole-organism tasks (e.g., running uphill), as the evolution of behavior (e.g., toe-furling) has enabled geckos to be superior climbers than anoles. We also show that adaptive increases in the toepad size within a closely related lizard genus (Anolis) has resulted in concomitant evolution of enhanced clinging ability and increased perch heights. A third insight is that pad-bearing geckos are capable of carrying tremendous loads (up to 250% of body weight) up smooth surfaces, and that the toepad itself does not appear limiting. This comparative and whole-organism approach to lizard toepads underscores how organisms can evolve multiple solutions to evolutionary problems.

Adaptation, Physiological↗

Evolutionary transformations of the fetal membranes of viviparous reptiles: a case study of two lineages.

The reptilian placenta is a composite structure formed by a functional interaction between extraembryonic membranes and the maternal uterus. Study of placental structure of squamate reptiles over the past century has established that each of the multiple independent origins of placentation, which characterize the reproductive diversity of squamates, has resulted from the evolutionary transformation of these homologous structures. Because each evolutionary transformation is an independent novel relationship between maternal and embryonic tissues, the resulting placentae are not homologous, even though the individual components may be. The evolution of reptilian placentation should reveal much about evolutionary patterns and mechanisms because similar structural-functional systems have been transformed along parallel trajectories on multiple occasions. We compared extraembryonic membrane and placental development and pattern of embryonic nutrition in thamnophiine snakes and Pseudemoia lizards in the context of recent hypotheses of phylogenetic relationships. Two primary types of placentation, chorioallantoic and yolk sac, evolved in each lineage. Smooth, highly vascular regions of chorioallantoic placentation are indistinguishable homoplasies that evolved in parallel, likely to facilitate respiratory exchange. The yolk sac placenta of each lineage is specialized for histotrophic nutrient transfer, yet composition of these structures differs because of variation in the ancestral snakes and lizards. In addition, the omphalopleure that contributes to yolk sac placentation persists to later embryonic stages compared to oviparous outgroups, but the two lineages have evolved different structures that prevent replacement of the omphalopleure by the allantois. Each lineage has also evolved unique structural specializations of the chorioallantoic placenta.

Allantois↗

The analysis of ontogenetic trajectories: when a change in size or shape is not heterochrony.

Heterochrony has become a central organizing concept relating development and evolution. Unfortunately, the standard definition of heterochrony--evolutionary change in the rate or timing of developmental processes--is so broad as to apply to any case of phenotypic evolution. Conversely, the standard classes of heterochrony only accurately describe a small subset of the possible ways that ontogeny can change. I demonstrate here that the nomenclature of heterochrony is meaningful only when there is a uniform change in the rate or timing of some ontogenetic process, with no change in the internal structure of that process. Given two ontogenetic trajectories, we can test for this restricted definition of heterochrony by asking if a uniform stretching or translation of one trajectory along the time axis superimposes it on the other trajectory. If so, then the trajectories are related by a uniform change in the rate or timing of development. If not, then there has been change within the ontogenetic process under study. I apply this technique to published data on fossil Echinoids and to the comparison of human and chimpanzee growth curves. For the Echinoids, some characters do show heterochrony (hypermorphosis), while others, which had previously been seen as examples of heterochrony, fail the test--implying that their evolution involved changes in the process of development, not just the rate at which it proceeded. Analysis of human and chimpanzee growth curves indicates a combination of neoteny and sequential hypermorphosis, two processes previously seen as alternate explanations for the differences between these species.

Animals↗

Skull ontogeny: developmental patterns of fishes conserved across major tetrapod clades.

In vertebrates, the ontogeny of the bony skull forms a particularly complex part of embryonic development. Although this area used to be restricted to neontology, recent discoveries of fossil ontogenies provide an additional source of data. One of the most detailed ossification sequences is known from Permo-Carboniferous amphibians, the branchiosaurids. These temnospondyls form a near-perfect link between the piscine osteichthyans and the various clades of extant tetrapods, retaining a full complement of dermal bones in the skull. For the first time, the broader evolutionary significance of these event sequences is analyzed, focusing on the identification of sequence heterochronies. A set of 120 event pairs was analyzed by event pair cracking, which helped identify active movers. A cladistic analysis of the event pair data was also carried out, highlighting some shared patterns between widely divergent clades of tetrapods. The analyses revealed an unexpected degree of similarity between the widely divergent taxa. Most interesting is the apparently modular composition of the cranial sequence: five clusters of bones were discovered in each of which the elements form in the same time window: (1) jaw bones, (2) marginal palatal elements, (3) circumorbital bones, (4) skull roof elements, and (5) neurocranial ossifications. In the studied taxa, these "modules" have in most cases been shifted fore and back on the trajectory relative to the Amia sequence, but did not disintegrate. Such "modules" might indicate a high degree of evolutionary limitation (constraint).

Amphibians↗

Relic behaviours, coevolution and the retention versus loss of host defences after episodes of avian brood parasitism.

Most previous studies of brood parasitism have stressed that host defences, such as egg recognition, are lost in the absence of parasitism. Such losses could result in coevolutionary cycles in which parasites shift away from well-defended hosts only to switch back to them later at a time when these hosts have lost much or all of their defences and the parasite's current hosts have built up effective defences. However, the alternative 'single trajectory' model predicts that parasites rarely switch back to old hosts because ex-hosts retain egg recognition for long periods in the absence of parasitism. If true, egg recognition by the host may be a 'relic behaviour', because in the absence of parasitism its adaptive value is close to neutral. Using artificial nonmimetic eggs, I tested for egg recognition in two populations that are currently unparasitized but that are descended from lineages likely to have been parasitized in the past: the grey catbird, Dumetella carolinensis, on Bermuda and the loggerhead shrike, Lanius ludovicianus, in California. Both of these populations showed long-term retention, ejecting nonmimetic eggs at rates of nearly 100%. Because potential present-day selection pressures, such as conspecific parasitism, do not explain this egg recognition, Bermuda catbirds apparently retain recognition from North American conspecifics that were cowbird hosts before colonizing Bermuda and shrikes retain recognition from Old World congeners that were hosts of cuckoos. Retention is also indicated by passerines in California and the Caribbean that had high rejection rates of nonmimetic eggs before coming into contact with cowbirds. These new data suggest that both the coevolutionary cycles and single trajectory models have importance and that rejection behaviour can have insignificant costs, which is consistent with evolutionary lag explanations for the acceptance of parasitic eggs shown by some cuckoo and many cowbird hosts. Copyright 2001 The Association for the Study of Animal Behaviour.

Journal Article↗

Stable simulations do not guarantee functional engagement: a case study of off-target prediction for Seladelpar and Zanamivir.

Identifying off-target interactions of approved drugs is important to anticipate side effects and uncover repurposing opportunities. Computational pipelines combining structural homology, structure prediction, and molecular dynamics (MD) simulations offer a promising strategy, but it remains unclear whether stable, control-like MD trajectories reliably indicate functional engagement. We examined this in a case study of two approved drugs. Using the Evolutionary Classification of Protein Domains (ECOD) framework to select candidate off-targets, we modeled each drug-protein complex as two independent AlphaFold3 models and simulated both by MD, for Seladelpar (a PPARδ agonist) and Zanamivir, an influenza neuraminidase inhibitor that also inhibits human Sialidase-2 (NEU2). Candidates were ranked by the similarity of global MD descriptors to the on-target control. For Seladelpar, the three top-ranked candidates (FXR, RARγ, ERRγ) were tested experimentally; the Zanamivir set was analyzed computationally only. None showed measurable activity in reporter or thermal shift assays, despite stable simulations and descriptor values comparable to the control. Including PPARα and PPARγ as weak-positive comparators, these descriptors did not rank genuine interactions closer to the control than inactive candidates. Residue-level comparison with experimental structures showed the predicted poses reproduced only part of the canonical contacts. Where experimental drug-bound structures existed, AlphaFold3 reproduced the pose for PPARα but not PPARγ, and its per-model confidence did not track pose accuracy. Within this case study, the specific global descriptors examined reflect complex stability rather than functional engagement, which does not mean MD-based approaches cannot make this distinction.

Zanamivir↗

The future of human spaceflight.

After the Apollo Moon program, the international space station represents a further milestone of humankind in space, International follow-on programs like a manned return to the Moon and a first manned Mars Mission can be considered as the next logical step. More and more attention is also paid to the topic of future space tourism in Earth orbit, which is currently under investigation in the USA, Japan and Europe due to its multibillion dollar market potential and high acceptance in society. The wide variety of experience, gained within the space station program, should be used in order to achieve time and cost savings for future manned programs. Different strategies and roadmaps are investigated for space tourism and human missions to the Moon and Mars, based on a comprehensive systems analysis approach. By using DLR's software tool FAST (Fast Assessment of Space Technologies), different scenarios will be defined, optimised and finally evaluated with respect to mission architecture, required technologies, total costs and program duration. This includes trajectory analysis, spacecraft design on subsystem level, operations and life cycle cost analysis. For space tourism, an expected evolutionary roadmap will be described which is initiated by short suborbital tourism and ends with visionary designs like the Space Hotel Berlin and the Space Hotel Europe concept. Furthermore the potential space tourism market, its economic meaning as well as the expected range of the costs of a space ticket (e.g. $50,000 for a suborbital flight) will be analysed and quantified. For human missions to the Moon and Mars, an international 20 year program for the first decades of the next millennium is proposed, which requires about $2.5 Billion per year for a manned return to the Moon program and about $2.6 Billion per year for the first 3 manned Mars missions. This is about the annual budget, which is currently spend by the USA only for the operations of its Space Shuttle fleet which generally proofs the affordability of such ambitious programs after the build-up of the International Space Station, when corresponding budget might become again available.

Equipment Design↗

Evolutionary optimization for robust hierarchical computation of the rotation centres of kinematic chains from reduced ranges of motion the lower spine case.

A novel technique based on evolutionary optimization is proposed here to compute the average rotation centres (RCs) of ball joints linked into kinematic chains using 3D trajectories of the markers attached to the external surface of the corresponding articulated structures. The chain is hierarchically solved by iteratively minimizing the variance of the marker distances from the actual RC through an evolutional strategy method (ESM) from proximal to distal joints. In particular, the technique is compared to the non-rigid sphere-fitting method, recently proposed in literature and implemented through a closed-form solution (CFS), in conditions of random and systematic noise superimposed to the marker coordinates. Results from simulated motions showed that, in case of small range of motion (5 degrees , 10 degrees ) the performance of CFS is really unreliable whereas ESM provided satisfactory accuracy. Error propagation along the kinematic chain was found to be negligible. Also in the case of systematic errors, ESM provides an accuracy that is sensibly better than that of the CFS. As a case study, ESM was applied to the in vivo computation of the RCs of the vertebrae in the lower spine region using a specific marker protocol. A set of spine movements by a normal adult male, recorded by an optoelectronic motion capture system, were processed with the developed method. The variability of the estimated average RCs was small (few millimeters) in agreement with the literature data from cadaveric studies and X-ray imaging.

Algorithms↗

Précis of "Lifelines: biology, freedom, determinism".

There are many ways of describing and explaining the properties of living systems; causal, functional, and reductive accounts are necessary but no one account has primacy. The history of biology as a discipline has given excessive authority to reductionism, which collapses higher level accounts, such as social or behavioural ones, into molecular ones. Such reductionism becomes crudely ideological when applied to the human condition, with its claims for genes "for" everything from sexual orientation to compulsive shopping. The current enthusiasm for genetics and ultra-Darwinist accounts, with their selfish-gene metaphors for living processes, misunderstand both the phenomena of development and the interactive role that DNA and the fluid genome play in the cellular orchestra. DNA is not a blueprint, and the four dimensions of life (three of space, one of time) cannot be read off from its one-dimensional strand. Both developmental and evolutionary processes are more than merely instructive or selective; the organism constructs itself, a process known as autopoiesis, through a lifeline trajectory. Because organisms are thermodynamically open systems, living processes are homeodynamic, not homeostatic. The self-organising membrane-bound and energy-utilising metabolic web of the cell must have evolved prior to socalled naked replicators. Evolution is constrained by physics, chemistry, and structure; not all change is powered by natural selection, and not all phenotypes are adaptive. Finally, therefore, living processes are radically indeterminate; like all other living organisms, but to an even greater degree, we make our own future, though in circumstances not of our own choosing.

Animals↗

A guide to understanding tumour evolution through the lens of population genetics.

Every cancer carries the history of its own evolution, hidden in its genome. Modern DNA sequencing can catalogue millions of mutations and profile tumours across space and time, but sequencing alone struggles to answer the questions that matter most: when did key adaptations emerge, how strongly were they selected, why do some tumours relapse whereas others do not, and how will the cancer evolve next? The reason is fundamental: sequencing is a snapshot, whereas evolution is a dynamic process. Bridging this gap requires moving beyond descriptive cancer genomics towards quantitative evolutionary inference. In this Review, we argue that population genetics provides the mathematical framework needed to extract evolutionary dynamics from cancer genomes. We show how models of mutation, selection and drift transform allele frequencies from descriptive measurements into quantitative estimates of clonal fitness and evolutionary timings. We discuss how these principles extend to epigenetic inheritance, plasticity and ecological interactions within the tumour ecosystem, and examine the assumptions and limitations for their application to modern sequencing data. By reframing cancer genomes as quantitative records of evolutionary processes rather than catalogues of mutations, researchers have used population genetics to provide a foundation for understanding - and ultimately predicting - the trajectories of cancer evolution.

Journal Article↗

Closed loops: persistence of the protein chain returns.

It has recently been discovered that globular proteins are universally built from standard loop-n-lock units of about 30 amino acid residues. The hypothesis has been put forward on the loop stage in the protein evolution when the units were autonomous. Later they joined together making longer chains. One would expect that the early individual loop-n-lock elements might still be detected in modern protein sequences as remnants of the hypothetical 30-residue sequence prototypes. Among several strong sequence motifs, extracted from protein sequences of 23 complete bacterial proteomes, one 32-residue prototype was studied here in detail. Numerous sequence segments related to the prototype are identified in the crystal structures of proteins of a PDB_SELECT database. Analysis of the respective chain trajectories for the cases with different degrees of sequence conservation confirms that the majority of the segments correspond to the closed loops. In the evolutionary diversification of the prototypes the secondary structure yields first, while the sequence is still moderately conserved. The last feature to go is the chain return property. Apparently, the opening of the loops would severely destabilize the protein fold, which explains their conservation.

Amino Acid Motifs↗

Evolution meets biopsychosociality: an analysis of addictive behavior.

Evolutionary theory can inform the biopsychosocial approach to addictive behavior through the use of adaptationist thinking, or how natural selection has shaped the mechanisms and processes underlying addiction. Covering how evolutionary theory relates to biology, psychology and sociality, this paper examines three components to drug use and abuse: a biological mechanism (mesolimbic dopamine), a developmental trajectory (attachment) and a social phylogeny (dominance, submission, social dependence). The paper argues for a salience (or wanting) view of the function of dopamine; outlines how attachment affects time perspective, closure of internal models and self-regulation; and examines how inequality affects drug abuse and how social dependence and manipulative behaviors can play a role in relationships with drugs. The article concludes with an analysis of how the adaptive approach applies to interventions against addictive behavior.

Adaptation, Psychological↗

Group-structured genetic models in analyses of the population and behavioral ecology of poikilothermic vertebrates.

Estimates of gene correlations among individuals within and among populations are frequently derived from statistical analyses of genetic data (e.g., F statistics). These measures can be important tools in molecular ecology and conservation, and offer important insights into population breeding structure. Using recently derived theory developed for group-structured populations, we show that fixation indices, when combined with basic population ecological and demographic data can be used to investigate population mating systems and to predict dispersal rates, trajectories and asymptotic levels of fixation indices, and effective population size. Four case studies of poikilothermic vertebrates are used to demonstrate the broad utility of evolutionary and ecological inferences afforded by group-structured models.

Animals↗

Structure alignment via Delaunay tetrahedralization.

A novel protein structure alignment technique has been developed reducing much of the secondary and tertiary structure to a sequential representation greatly accelerating many structural computations, including alignment. Constructed from incidence relations in the Delaunay tetrahedralization, alignments of the sequential representation describe structural similarities that cannot be expressed with rigid-body superposition and complement existing techniques minimizing root-mean-squared distance through superposition. Restricting to the largest substructure superimposable by a single rigid-body transformation determines an alignment suitable for root-mean-squared distance comparisons and visualization. Restricted alignments of a test set of histones and histone-like proteins determined superpositions nearly identical to those produced by the established structure alignment routines of DaliLite and ProSup. Alignment of three, increasingly complex proteins: ferredoxin, cytidine deaminase, and carbamoyl phosphate synthetase, to themselves, demonstrated previously identified regions of self-similarity. All-against-all similarity index comparisons performed on a test set of 45 class I and class II aminoacyl-tRNA synthetases closely reproduced the results of established distance matrix methods while requiring 1/16 the time. Principal component analysis of pairwise tetrahedral decomposition similarity of 2300 molecular dynamics snapshots of tryptophanyl-tRNA synthetase revealed discrete microstates within the trajectory consistent with experimental results. The method produces results with sufficient efficiency for large-scale multiple structure alignment and is well suited to genomic and evolutionary investigations where no geometric model of similarity is known a priori.

Algorithms↗