Evo-devo and the search for homology (“sameness”) in biological systems

Developmental biology and evolutionary studies have merged into evolutionary developmental biology (“evo-devo”). This synthesis already influenced and still continues to change the conceptual framework of structural biology. One of the cornerstones of structural biology is the concept of homology. But the search for homology (“sameness”) of biological structures depends on our favourite perspectives (axioms, paradigms). Five levels of homology (“sameness”) can be identified in the literature, although they overlap to some degree: (i) serial homology (homonomy) within modular organisms, (ii) historical homology (synapomorphy), which is taken as the only acceptable homology by many biologists, (iii) underlying homology (i.e., parallelism) in closely related taxa, (iv) deep evolutionary homology due to the “same” master genes in distantly related phyla, and (v) molecular homology exclusively at gene level. The following essay gives emphasis on the heuristic advantages of seemingly opposing perspectives in structural biology, with examples mainly from comparative plant morphology. The organization of the plant body in the majority of angiosperms led to the recognition of the classical root–shoot model. In some lineages bauplan rules were transcended during evolution and development. This resulted in morphological misfits such as the Podostemaceae, peculiar eudicots adapted to submerged river rocks. Their transformed “roots” and “shoots” fit only to a limited degree into the classical model which is based on either–or thinking. It has to be widened into a continuum model by taking over elements of fuzzy logic and fractal geometry to accommodate for lineages such as the Podostemaceae.     

The molecular basis of venom resistance in a rattlesnake‐squirrel predator‐prey system

Understanding how interspecific interactions mould the molecular basis of adaptations in coevolving species is a long‐sought goal of evolutionary biology. Venom in predators and venom resistance proteins in prey are coevolving molecular phenotypes, and while venoms are highly complex mixtures it is unclear if prey respond with equally complex resistance traits. Here, we use a novel molecular methodology based on protein affinity columns to capture and identify candidate blood serum resistance proteins (“venom interactive proteins” [VIPs]) in California Ground Squirrels (Otospermophilus beecheyi) that interact with venom proteins from their main predator, Northern Pacific Rattlesnakes (Crotalus o. oreganus). This assay showed that serum‐based resistance is both population‐ and species‐specific, with serum proteins from ground squirrels showing higher binding affinities for venom proteins of local snakes compared to allopatric individuals. Venom protein specificity assays identified numerous and diverse candidate prey resistance VIPs but also potential targets of venom in prey tissues. Many specific VIPs bind to multiple snake venom proteins and, conversely, single venom proteins bind multiple VIPs, demonstrating that a portion of the squirrel blood serum “resistome” involves broad‐based inhibition of nonself proteins and suggests that resistance involves a toxin scavenging mechanism. Analyses of rates of evolution of VIP protein homologues in related mammals show that most of these proteins evolve under purifying selection possibly due to molecular constraints that limit the evolutionary responses of prey to rapidly evolving snake venom proteins. Our method represents a general approach to identify specific proteins involved in co‐evolutionary interactions between species at the molecular level.     

Russian comparative embryology takes form: a conceptual metamorphosis toward “evo‐devo”

This essay recapitulates major paths followed by the Russian tradition of what we refer to today as evolutionary developmental biology (“evo‐devo”). The article addresses several questions regarding the conceptual history of evolutionary embryological thought in its particularly Russian perspective: (1) the assertion by the St. Petersburg academician Wolff regarding the possible connections between environmental modifications during morphogenesis and the “transformation” of species, (2) the discovery of shared “principles” underlying animal development by von Baer, (3) the experimental expression of Baer's principles by Kowalevsky and Mechnikoff, (4) Severtsov's theory of phylembryogenesis, (5) Filatov's approach to the study of evolution using comparative “developmental mechanics”, and (6) Shmalgausen's concept of “stabilizing” selection as an attempt to elucidate the evolution of developmental mechanisms. The focus on comparative evolutionary embryology, which was established by Kowalevsky and Mechnikoff, still continues to be popular in present‐day “evo‐devo” research in Russia.     

Phenoptosis as genetically determined aging influenced by signals from the environment

Aging is a complex and not well understood process. Two opposite concepts try to explain its causes and mechanisms — programmed aging and aging of “wear and tear” (stochastic aging). To date, much evidence has been obtained that contradicts the theories of aging as being due to accumulation of various damages. For example, creation of adequate conditions for the functioning of the organism’s components (appropriate microenvironment, humoral background, etc.) has been shown to cause partial or complete reversibility of signs of its aging. Programmed aging and death of an organism can be termed phenoptosis by analogy to the term apoptosis for programmed cell death (this term was first suggested by V. P. Skulachev). The necessity of this phenomenon, since A. Weismann, has been justified by the need for population renewal according to ecological and evolutionary requirements. Species-specific lifespan, age-dependent changes in expression pattern of genes, etc. are compatible with the concept of phenoptosis. However, the intraspecific rate of aging was shown to vary over of a wide range depending on living conditions. This means that the “aging program” is not set rigidly; it sensitively adjusts an individual to the specific realities of its habitat. Moreover, there are indications that in rather severe conditions of natural habitat the aging program can be completely cancelled, as the need for it disappears because of the raised mortality from external causes (high extrinsic mortality), providing fast turnover of the population.     

A new method for describing predator-prey relations in discontinous environments

I propose a new method for anlysing predatorprey interactive systems in discontinuous environments. The basic index used here is a generalized version ofLloyd 's (1967) “interspecies mean crowding”, which is defined as the number of individuals of one species existing in a given patch per that of the other species in either the same or different patches at either the same or different times. Four indices are derived from different combinations of the numbers of the prey and the predator in habitat patches. Then, the correlation coefficients between the numbers of individuals in patches in both different locations and times are derived by modifying the above new indices. Using this technique, dynamical changes of the joint distributions of the numbers of predators and prey which reflect variation in local conditions, can readily be described. As an example, this method was applied to an analysis of the outcomes of a multi-patch version of theLotka-Volterra model of predator-prey interactions.     

Antagonistic evolution in an aposematic predator–prey signaling system

Warning signals within species, such as the bright colors of chemically defended animals, are usually considered mutualistic, monomorphic traits. Such a view is however increasingly at odds with the growing empirical literature, showing nontrivial levels of signal variation within prey populations. Key to understanding this variation, we argue, could be a recognition that toxicity levels frequently vary within populations because of environmental heterogeneity. Inequalities in defense may undermine mutualistic monomorphic signaling, causing evolutionary antagonism between loci that determine appearance of less well‐defended and better defended prey forms within species. In this article, we apply a stochastic model of evolved phenotypic plasticity to the evolution of prey signals. We show that when toxicity levels vary, then antagonistic interactions can lead to evolutionary conflict between alleles at different signaling loci, causing signal evolution, “red queen‐like” evolutionary chase, and one or more forms of signaling equilibria. A key prediction is that variation in the way that predators use information about toxicity levels in their attack behaviors profoundly affects the evolutionary characteristics of the prey signaling systems. Environmental variation is known to cause variation in many qualities that organisms signal; our approach may therefore have application to other signaling systems.     

Wild GWAS—association mapping in natural populations

The increasing affordability of sequencing and genotyping technologies has transformed the field of molecular ecology in recent decades. By correlating marker variants with trait variation using association analysis, large‐scale genotyping and phenotyping of individuals from wild populations has enabled the identification of genomic regions that contribute to phenotypic differences among individuals. Such “gene mapping” studies are enabling us to better predict evolutionary potential and the ability of populations to adapt to challenges, such as changing environment. These studies are also allowing us to gain insight into the evolutionary processes maintaining variation in natural populations, to better understand genotype‐by‐environment and epistatic interactions and to track the dynamics of allele frequency change at loci contributing to traits under selection. Gene mapping in the wild using genomewide association scans (GWAS) do, however, come with a number of methodological challenges, not least the population structure in space and time inherent to natural populations. We here provide an overview of these challenges, summarize the exciting methodological advances and applications of association mapping in natural populations reported in this special issue and provide some guidelines for future “wild GWAS” research.     

When will evolution lead to deceptive signaling in the Sir Philip Sidney game?

Sir Philip Sidney games are a widely used model of simple signaling. Johnstone and Grafen [Johnstone, R.A., Grafen, A., 1993. Dishonesty and the handicap principle. Animal Behaviour 46, 759–764] present a version in which the Evolutionarily Stable Strategy (ESS) is for most signalers to “honestly” signal, with a small minority of signalers who “cheat”. This model is among the most frequently cited papers on the topic of “dishonest” signaling and supports the view that signals may be “dishonest” as long as they are “honest on average”. Using genetic algorithms, we demonstrate that another solution exists to the game, an evolutionarily stable set of Nash equilibria in which members of the set never signal and all donors give their resource. Payoffs to players using this set of strategies is greater those when playing the “dishonest” signaling ESS. We demonstrate that a random population is far more likely to evolve to this non-communicating strategy set than the “dishonest” signaling ESS. We also discuss the dynamics of biological game theory models and the advances of genetic algorithms as a heuristic solution method for these models.     

Fine‐scale spatial differences in humpback whale diet composition near Kodiak,Alaska

On the North Pacific feeding grounds, humpback whales (Megaptera novaeangliae) are recovering from commercial whaling at a rapid rate (6.8%). The potential effect that this recovery will have on trophic dynamics involving these predators is currently unknown. To better elucidate complex trophic dynamics, variability in diet composition of apex predators on their respective feeding grounds needs to be understood. Thus, we explored the diet composition of two defined subaggregations of humpback whales of the Kodiak Archipelago population (“North,” “South”) using stable carbon (δ¹³C) and nitrogen (δ¹⁵N) isotope ratios of humpback whale skin and regional prey samples in Bayesian dietary mixing models. Humpback whales in the “North” region consumed proportionally more fish, dominated by capelin (Mallotus villosus), whereas, whales in the “South” region consumed predominantly krill. The difference in diet composition appears to reflect regional differences in prey availability. Thus, regional variability in diet composition by humpback whales may have disproportionate impacts on prey resources of sympatric predators depending on available prey biomass. As a result, we suggest fine‐scale studies of apex predator diets are needed to better model trophic dynamics with accuracy.     

Transcriptome analysis reveals the difference between “healthy” and “common” aging and their connection with age‐related diseases

A key goal of aging research was to understand mechanisms underlying healthy aging and develop methods to promote the human healthspan. One approach is to identify gene regulations unique to healthy aging compared with aging in the general population (i.e., “common” aging). Here, we leveraged Genotype‐Tissue Expression (GTEx) project data to investigate “healthy” and “common” aging gene expression regulations at a tissue level in humans and their interconnection with diseases. Using GTEx donors' disease annotations, we defined a “healthy” aging cohort for each tissue. We then compared the age‐associated genes derived from this cohort with age‐associated genes from the “common” aging cohort which included all GTEx donors; we also compared the “healthy” and “common” aging gene expressions with various disease‐associated gene expressions to elucidate the relationships among “healthy,” “common” aging and disease. Our analyses showed that 1. GTEx “healthy” and “common” aging shared a large number of gene regulations; 2. Despite the substantial commonality, “healthy” and “common” aging genes also showed distinct function enrichment, and “common” aging genes had a higher enrichment for disease genes; 3. Disease‐associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with some “healthy” aging gene regulations. In summary, our work highlights several unique features of GTEx “healthy” aging program. This new knowledge could potentially be used to develop interventions to promote the human healthspan.     

Mothers' Egg-pooling and Aposematic Offspring's Gregariousness: Cui bono?

Recently Sillén-Tullberg & Leimar (1988) modelled a general explanation for the evolution of gregariousness in prey organisms that live exposed, have no means of escape when discovered by a predator, and are small in relation to a potential predator (who thus can sample many prey individuals in one encounter). The model predicts that gregarious prey organisms of that type ought to be distasteful, and that the evolution of gregariousness will be favoured by aposematic coloration facilitating avoidance learning in a predator. Obviously, any protective power of grouping depends on group size. According to the Sillén-Tullberg & Leimar model, (1) “members of small groups may have a higher rate of death from predation than solitary individuals, but above a certain minimum group size, group members do better than solitary individuals; … as group size increases above the minimum value, group members suffer fewer and fewer deaths from predation”. They benefit from the “decreased risk of predator attack on any particular individual”, called dilution effect. (2) “The more prey specimens that the predator needs to sample during avoidance learning, the larger an aggregation needs to be in order for gregariousness to be advantageous”. It is further explained that (3) selection resulting from predation favours increase in group size until it “acts like a predator-satiation mechanism”.     

Development of evolutionary biomedicine as a novel direction of biological science

This review analyzes the data obtained for the last decade on invertebrate animals (insects, round worms, molluscs) as models of various human diseases. As illustration, there are considered advances in studying of the invertebrate system of insulin-like peptides and signaling mechanisms of their action—evolutionary conservative homologues of the mammalian insulin/IGF-1 system. Results are presented of studies on the nematode Caenorhabditis elegans, Drosophila Drosophila melanogaster, and mollusks, which “model” individual aspects of some human diseases—diabetes, neurodegenerative dysfunction, carcinogenesis, as well as aging. A conclusion is made about the development of a new, synthetic direction combining evolutionary science and molecular biology and medicine, which we call evolutionary biomedicine. The roots of the appearance of this synthetic direction are to be searched for in L.A. Orbeli’s evolutionary ideas, methods, and scientific predictions.     

Programmed aging of mammals: Proof of concept and prospects of biochemical approaches for anti-aging therapy

(i) In 2015-2017 we compared possible reasons for longevity of two mammalian highly social species, i.e. naked mole rats and humans. We proposed that in both cases longevity is a result of neoteny, prolongation of youth by deceleration of late ontogeny (Skulachev, V. P. (2015) Abst. 11th Conf. on Mitochondrial Physiology (MiP2015), Lucni Bouda, Czech Republic, pp. 64-66; Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakeeva, L. E., Skulachev, M. V., Markov, A. V., Hildebrandt, T. B., and Sadovnichii, V. A. (2017) Physiol. Rev., 97, 699-720). Both naked mole rats and humans strongly decreased the pressure of natural selection, although in two different manners. Naked mole rats preferred an “aristocratic” pathway when reproduction (and, hence, involvement in evolution) is monopolized by the queen and her several husbands. Huge number of subordinates who have no right to take part in reproduction and hence in evolution serves the small queen’s family. Humans used an alternative, “democratic” pathway, namely technical progress facilitating adaptation to the changing environmental conditions. This pathway is open to all humankind. (ii) As a result, aging as a mechanism increasing evolvability by means of facilitation of natural selection became unnecessary for naked mole rats and humans due to strong attenuation of this selection. This is apparently why aging became a counterproductive atavism for these two species and was strongly shifted to late ages. This shift is direct evidence of the hypothesis that aging is programmed, being the last step of late ontogeny. (iii) Further deceleration of aging for humans by means of neoteny is unrealistic since the development of neoteny probably takes million years. (iv) However, if biological aging is a program, an alternative and much simpler way to avoid it seems possible. We mean inhibition of an essential step of this program. (v) At present, the most probable scheme of the aging program assumes that it is a mechanism of slow poisoning of an organism by reactive oxygen species produced by mitochondria. If this is the case, a mitochondria-targeted antioxidant might be an inhibitor of the aging program. During the last 12 years, such an antioxidant, namely SkQ1, was synthesized and studied in detail in our group. It consists of plastoquinone and decyltriphenylphosphonium (a penetrating cation responsible for electrophoretic accumulation of SkQ1 in mitochondria). It was shown that long-term treatment with SkQ1 increased the lifespan of plants, fungi, invertebrates, fish, and mammals. Moreover, SkQ1 is effective in the therapy of various age-related diseases. It was also shown that a single SkQ1 injection could save life in certain models of sudden death of animals. (vi) A tentative scheme is proposed considering aging as a process of chronic phenoptosis, which eventually results in initiation of acute phenoptosis and death. This scheme also suggests that under certain conditions chronic phenoptosis can be neutralized by an anti-aging program that is activated by food restriction regarded by an organism as a signal of starvation. As for acute phenoptosis, it is apparently controlled by receptors responsible for measuring key parameters of homeostasis. The first experimental indications have been already obtained indicating that both chronic and acute phenoptosis are suppressed by SkQ1.     

Pulsed-resource dynamics constrain the evolution of predator-prey interactions

Although temporal variability in the physical environment plays a major role in population fluctuations, little is known about how it drives the ecological and evolutionary dynamics of species interactions. We studied experimentally how extrinsic resource pulses affect evolutionary and ecological dynamics between the prey bacterium Serratia marcescens and the predatory protozoan Tetrahymena thermophila. Predation increased the frequency of defensive, nonpigmented prey types, which bore competitive costs in terms of reduced maximum growth rate, most in a constant-resource environment. Furthermore, the predator densities of the pulsed-resource environment regularly fluctuated above and below the mean predator densities of the constant environment. These results suggest that selection favored fast-growing competitor prey types over defensive but slower-growing prey types more often in the pulsed-resource environment (abundance of resources and low predation risk). As a result, the selection for prey defense fluctuated more in the pulsed-resource environment, leading to a weaker mean response in prey defense. At the ecological level, the evolution of prey defense weakened the relative strength of top-down regulation on prey community. This was more evident in the constant-resource environment, whereas the slow emergence of defensive prey types gradually decreased the amplitude of predator peaks in the pulsed-resource environment. Our study suggests that rapid evolution plays a smaller role in the ecological dynamics of communities dominated by resource pulses.     

A predator–prey refuge system: Evolutionary stability in ecological systems

A refuge model is developed for a single predator species and either one or two prey species where no predators are present in the prey refuge. An individual’s fitness depends on its strategy choice or ecotype (predators decide which prey species to pursue and prey decide what proportion of their time to spend in the refuge) as well as on the population sizes of all three species. It is shown that, when there is a single prey species with a refuge or two prey species with no refuge compete only indirectly (i.e. there is only apparent competition between prey species), that stable resident systems where all individuals in each species have the same ecotype cannot be destabilized by the introduction of mutant ecotypes that are initially selectively neutral. In game-theoretic terms, this means that stable monomorphic resident systems, with ecotypes given by a Nash equilibrium, are both ecologically and evolutionarily stable. However, we show that this is no longer the case when the two indirectly-competing prey species have a refuge. This illustrates theoretically that two ecological factors, that are separately stabilizing (apparent competition and refuge use), may have a combined destabilizing effect from the evolutionary perspective. These results generalize the concept of an evolutionarily stable strategy (ESS) to models in evolutionary ecology. Several biological examples of predator–prey systems are discussed from this perspective.     

Thinking in continua: beyond the “adaptive radiation” metaphor

“Adaptive radiation” is an evocative metaphor for explosive evolutionary divergence, which for over 100 years has given a powerful heuristic to countless scientists working on all types of organisms at all phylogenetic levels. However, success has come at the price of making “adaptive radiation” so vague that it can no longer reflect the detailed results yielded by powerful new phylogeny‐based techniques that quantify continuous adaptive radiation variables such as speciation rate, phylogenetic tree shape, and morphological diversity. Attempts to shoehorn the results of these techniques into categorical “adaptive radiation: yes/no” schemes lead to reification, in which arbitrary quantitative thresholds are regarded as real. Our account of the life cycle of metaphors in science suggests that it is time to exchange the spent metaphor for new concepts that better represent the full range of diversity, disparity, and speciation rate across all of life.     

Environmental stress maintains trioecy in nematode worms

Sex is determined by chromosomes in mammals but it can be influenced by the environment in many worms, crustaceans, and vertebrates. Despite this, there is little understanding of the relationship between ecology and the evolution of sexual systems. The nematode Auanema freiburgensis has a unique sex determination system in which individuals carrying one X chromosome develop into males while XX individuals develop into females in stress-free environments and self-fertile hermaphrodites in stressful environments. Theory predicts that trioecious populations with coexisting males, females, and hermaphrodites should be unstable intermediates in evolutionary transitions between mating systems. In this article, we study a mathematical model of reproductive evolution based on the unique life history and sex determination of A. freiburgensis. We develop the model in two scenarios, one where the relative production of hermaphrodites and females is entirely dependent on the environment and one based on empirical measurements of a population that displays incomplete, “leaky” environmental dependence. In the first scenario environmental conditions can push the population along an evolutionary continuum and result in the stable maintenance of multiple reproductive systems. The second “leaky” scenario results in the maintenance of three sexes for all environmental conditions. Theoretical investigations of reproductive system transitions have focused on the evolutionary costs and benefits of sex. Here, we show that the flexible sex determination system of A. freiburgensis may contribute to population-level resilience in the microscopic nematode's patchy, ephemeral natural habitat. Our results demonstrate that life history, ecology, and environment may play defining roles in the evolution of sexual systems.     

Stabilizing effects of spatial heterogeneity in predator-prey systems

A general predator is assumed to divide its hunting time between two sub-habitats with different prey species, spending a larger fraction (φ) of search time in an area as the relative prey abundance there increases. This always causes switching in the model, and changes a functional response from one that imposes a risk on the average prey that decreases with prey density in the direction of one that imposes an increasing risk. I discuss the conditions for a response that is density dependent, and those predatory attributes that make such a response more likely. Transit time between subhabitats always increases the density dependent effect, and is necessary for “system stability” in a Lotka-Volterra model with two prey species. Experiments have confirmed the model's basic assumption. General predators do not fit easily into classical predator-prey models of simple “closed” communities, and then the degree of density dependence of the functional response becomes a useful measure of a predator's short-term stabilizing effect on a prey species. The model demonstrates how spatial heterogeneity can be stabilizing.     

Diversification in evolutionary arenas—Assessment and synthesis

Understanding how and why rates of evolutionary diversification vary is a key issue in evolutionary biology, ecology, and biogeography. Evolutionary rates are the net result of interacting processes summarized under concepts such as adaptive radiation and evolutionary stasis. Here, we review the central concepts in the evolutionary diversification literature and synthesize these into a simple, general framework for studying rates of diversification and quantifying their underlying dynamics, which can be applied across clades and regions, and across spatial and temporal scales. Our framework describes the diversification rate (d) as a function of the abiotic environment (a), the biotic environment (b), and clade‐specific phenotypes or traits (c); thus, d ~ a,b,c. We refer to the four components (a–d) and their interactions collectively as the “Evolutionary Arena.” We outline analytical approaches to this framework and present a case study on conifers, for which we parameterize the general model. We also discuss three conceptual examples: the Lupinus radiation in the Andes in the context of emerging ecological opportunity and fluctuating connectivity due to climatic oscillations; oceanic island radiations in the context of island formation and erosion; and biotically driven radiations of the Mediterranean orchid genus Ophrys. The results of the conifer case study are consistent with the long‐standing scenario that low competition and high rates of niche evolution promote diversification. The conceptual examples illustrate how using the synthetic Evolutionary Arena framework helps to identify and structure future directions for research on evolutionary radiations. In this way, the Evolutionary Arena framework promotes a more general understanding of variation in evolutionary rates by making quantitative results comparable between case studies, thereby allowing new syntheses of evolutionary and ecological processes to emerge.     

The evolution of phenotypic traits in a predator-prey system subject to Allee effect

This paper considers the evolution of phenotypic traits in a community comprising the populations of predators and prey subject to Allee effect. The evolutionary model is constructed from a deterministic approximation of the stochastic process of mutation and selection. Firstly, we investigate the ecological and evolutionary conditions that allow for continuously stable strategy and evolutionary branching. We find that the strong Allee effect of prey facilitates the formation of continuously stable strategy in the case that prey population undergoes evolutionary branching if the Allee effect of prey is not strong enough. Secondly, we show that evolutionary suicide is impossible for prey population when the intraspecific competition of prey is symmetric about the origin. However, evolutionary suicide can occur deterministically on prey population if prey individuals undergo strong asymmetric competition and are subject to Allee effect. Thirdly, we show that the evolutionary model with symmetric interactions admits a stable limit cycle if the Allee effect of prey is weak. Evolutionary cycle is a likely outcome of the process, which depends on the strength of Allee effect and the mutation rates of predators and prey.