Maternal–fetal conflict,genomic imprinting and mammalian vulnerabilities to cancer

Antagonistic coevolution between maternal and fetal genes, and between maternally and paternally derived genes may have increased mammalian vulnerability to cancer. Placental trophoblast has evolved to invade maternal tissues and evade structural and immunological constraints on its invasion. These adaptations can be co-opted by cancer in intrasomatic selection. Imprinted genes of maternal and paternal origin favour different degrees of proliferation of particular cell types in which they reside. As a result, the set of genes favouring greater proliferation will be selected to evade controls on cell-cycle progression imposed by the set of genes favouring lesser proliferation. The dynamics of stem cell populations will be a particular focus of this intragenomic conflict. Gene networks that are battlegrounds of intragenomic conflict are expected to be less robust than networks that evolve in the absence of conflict. By these processes, maternal–fetal and intragenomic conflicts may undermine evolved defences against cancer.     

Sexual selection modulates genetic conflicts and patterns of genomic imprinting

Recent years have seen a surge of interest in linking the theories of kin selection and sexual selection. In particular, there is a growing appreciation that kin selection, arising through demographic factors such as sex‐biased dispersal, may modulate sexual conflicts, including in the context of male–female arms races characterized by coevolutionary cycles. However, evolutionary conflicts of interest need not only occur between individuals, but may also occur within individuals, and sex‐specific demography is known to foment such intragenomic conflict in relation to social behavior. Whether and how this logic holds in the context of sexual conflict—and, in particular, in relation to coevolutionary cycles—remains obscure. We develop a kin‐selection model to investigate the interests of different genes involved in sexual and intragenomic conflict, and we show that consideration of these conflicting interests yields novel predictions concerning parent‐of‐origin specific patterns of gene expression and the detrimental effects of different classes of mutation and epimutation at loci underpinning sexually selected phenotypes.     

The X chromosome favors males under sexually antagonistic selection

The X chromosome is found twice as often in females as males. This has led to an intuition that X‐linked genes for traits experiencing sexually antagonistic selection should tend to evolve toward the female optimum. However, this intuition has never been formally examined. In this paper, I present a simple mathematical model and ask whether the X chromosome is indeed biased toward effecting female‐optimal phenotypes. Counter to the intuition, I find that the exact opposite bias exists; the X chromosome is revealed to be a welcome spot for mutations that benefit males at the expense of females. Not only do male‐beneficial alleles have an easier time of invading and spreading through a population, but they also achieve higher equilibrium frequencies than comparable female‐beneficial alleles. The X chromosome is therefore expected over evolutionary time to nudge phenotypes closer to the male optimum. Consequently, the X chromosome should find itself engaged in perpetual intragenomic conflicts with the autosomes and the mitochondria over developmental outcomes. The X chromosome's male bias and the intragenomic conflicts that ensue bear on the evolution of gene regulation, speciation, and our concept of organismality.     

Running with the Red Queen: the role of biotic conflicts in evolution

What are the causes of natural selection? Over 40 years ago, Van Valen proposed the Red Queen hypothesis, which emphasized the primacy of biotic conflict over abiotic forces in driving selection. Species must continually evolve to survive in the face of their evolving enemies, yet on average their fitness remains unchanged. We define three modes of Red Queen coevolution to unify both fluctuating and directional selection within the Red Queen framework. Empirical evidence from natural interspecific antagonisms provides support for each of these modes of coevolution and suggests that they often operate simultaneously. We argue that understanding the evolutionary forces associated with interspecific interactions requires incorporation of a community framework, in which new interactions occur frequently. During their early phases, these newly established interactions are likely to drive fast evolution of both parties. We further argue that a more complete synthesis of Red Queen forces requires incorporation of the evolutionary conflicts within species that arise from sexual reproduction. Reciprocally, taking the Red Queen''s perspective advances our understanding of the evolution of these intraspecific conflicts.     

Why Darwin would have loved evolutionary game theory

Humans have marvelled at the fit of form and function, the way organisms'' traits seem remarkably suited to their lifestyles and ecologies. While natural selection provides the scientific basis for the fit of form and function, Darwin found certain adaptations vexing or particularly intriguing: sex ratios, sexual selection and altruism. The logic behind these adaptations resides in frequency-dependent selection where the value of a given heritable phenotype (i.e. strategy) to an individual depends upon the strategies of others. Game theory is a branch of mathematics that is uniquely suited to solving such puzzles. While game theoretic thinking enters into Darwin''s arguments and those of evolutionists through much of the twentieth century, the tools of evolutionary game theory were not available to Darwin or most evolutionists until the 1970s, and its full scope has only unfolded in the last three decades. As a consequence, game theory is applied and appreciated rather spottily. Game theory not only applies to matrix games and social games, it also applies to speciation, macroevolution and perhaps even to cancer. I assert that life and natural selection are a game, and that game theory is the appropriate logic for framing and understanding adaptations. Its scope can include behaviours within species, state-dependent strategies (such as male, female and so much more), speciation and coevolution, and expands beyond microevolution to macroevolution. Game theory clarifies aspects of ecological and evolutionary stability in ways useful to understanding eco-evolutionary dynamics, niche construction and ecosystem engineering. In short, I would like to think that Darwin would have found game theory uniquely useful for his theory of natural selection. Let us see why this is so.     

Gould talking past Dawkins on the unit of selection issue

My general aim is to clarify the foundational difference between Stephen Jay Gould and Richard Dawkins concerning what biological entities are the units of selection in the process of evolution by natural selection. First, I recapitulate Gould’s central objection to Dawkins’s view that genes are the exclusive units of selection. According to Gould, it is absurd for Dawkins to think that genes are the exclusive units of selection when, after all, genes are not the exclusive interactors: those agents directly engaged with, directly impacted by, environmental pressures. Second, I argue that Gould’s objection still goes through even when we take into consideration Sterelny and Kitcher’s defense of gene selectionism in their admirable paper “The Return of the Gene.” Third, I propose a strategy for defending Dawkins that I believe obviates Gould’s objection. Drawing upon Elisabeth Lloyd’s careful taxonomy of the various understandings of the unit of selection at play in the philosophy of biology literature, my proposal involves realizing that Dawkins endorses a different understanding of the unit of selection than Gould holds him to, an understanding that does not require genes to be the exclusive interactors.     

The beak of the other finch: coevolution of genetic covariance structure and developmental modularity during adaptive evolution

The link between adaptation and evolutionary change remains the most central and least understood evolutionary problem. Rapid evolution and diversification of avian beaks is a textbook example of such a link, yet the mechanisms that enable beak''s precise adaptation and extensive adaptability are poorly understood. Often observed rapid evolutionary change in beaks is particularly puzzling in light of the neo-Darwinian model that necessitates coordinated changes in developmentally distinct precursors and correspondence between functional and genetic modularity, which should preclude evolutionary diversification. I show that during first 19 generations after colonization of a novel environment, house finches (Carpodacus mexicanus) express an array of distinct, but adaptively equivalent beak morphologies—a result of compensatory developmental interactions between beak length and width in accommodating microevolutionary change in beak depth. Directional selection was largely confined to the elimination of extremes formed by these developmental interactions, while long-term stabilizing selection along a single axis—beak depth—was mirrored in the structure of beak''s additive genetic covariance. These results emphasize three principal points. First, additive genetic covariance structure may represent a historical record of the most recurrent developmental and functional interactions. Second, adaptive equivalence of beak configurations shields genetic and developmental variation in individual components from depletion by natural selection. Third, compensatory developmental interactions among beak components can generate rapid reorganization of beak morphology under novel conditions and thus greatly facilitate both the evolution of precise adaptation and extensive diversification, thereby linking adaptation and adaptability in this classic example of Darwinian evolution.     

What is natural selection?

‘Natural selection’ is, it seems, an ambiguous term. It is sometimes held to denote a consequence of variation, heredity, and environment, while at other times as denoting a force that creates adaptations. I argue that the latter, the force interpretation, is a redundant notion of natural selection. I will point to difficulties in making sense of this linguistic practise, and argue that it is frequently at odds with standard interpretations of evolutionary theory. I provide examples to show this; one example involving the relation between adaptations and other traits, and a second involving the relation between selection and drift.     

Key questions in the genetics and genomics of eco-evolutionary dynamics

Increasing acceptance that evolution can be ‘rapid'' (or ‘contemporary'') has generated growing interest in the consequences for ecology. The genetics and genomics of these ‘eco-evolutionary dynamics'' will be—to a large extent—the genetics and genomics of organismal phenotypes. In the hope of stimulating research in this area, I review empirical data from natural populations and draw the following conclusions. (1) Considerable additive genetic variance is present for most traits in most populations. (2) Trait correlations do not consistently oppose selection. (3) Adaptive differences between populations often involve dominance and epistasis. (4) Most adaptation is the result of genes of small-to-modest effect, although (5) some genes certainly have larger effects than the others. (6) Adaptation by independent lineages to similar environments is mostly driven by different alleles/genes. (7) Adaptation to new environments is mostly driven by standing genetic variation, although new mutations can be important in some instances. (8) Adaptation is driven by both structural and regulatory genetic variation, with recent studies emphasizing the latter. (9) The ecological effects of organisms, considered as extended phenotypes, are often heritable. Overall, the study of eco-evolutionary dynamics will benefit from perspectives and approaches that emphasize standing genetic variation in many genes of small-to-modest effect acting across multiple traits and that analyze overall adaptation or ‘fitness''. In addition, increasing attention should be paid to dominance, epistasis and regulatory variation.     

Coevolution Drives the Emergence of Complex Traits and Promotes Evolvability

The evolution of complex organismal traits is obvious as a historical fact, but the underlying causes—including the role of natural selection—are contested. Gould argued that a random walk from a necessarily simple beginning would produce the appearance of increasing complexity over time. Others contend that selection, including coevolutionary arms races, can systematically push organisms toward more complex traits. Methodological challenges have largely precluded experimental tests of these hypotheses. Using the Avida platform for digital evolution, we show that coevolution of hosts and parasites greatly increases organismal complexity relative to that otherwise achieved. As parasites evolve to counter the rise of resistant hosts, parasite populations retain a genetic record of past coevolutionary states. As a consequence, hosts differentially escape by performing progressively more complex functions. We show that coevolution''s unique feedback between host and parasite frequencies is a key process in the evolution of complexity. Strikingly, the hosts evolve genomes that are also more phenotypically evolvable, similar to the phenomenon of contingency loci observed in bacterial pathogens. Because coevolution is ubiquitous in nature, our results support a general model whereby antagonistic interactions and natural selection together favor both increased complexity and evolvability.     

GOOD GENES AND DIRECT SELECTION IN THE EVOLUTION OF MATING PREFERENCES

A model is used to study quantitatively the impact of a good genes process and direct natural selection on the evolution of a mating preference. The expression of a male display trait is proportional to genetic quality, which is determined by the number of deleterious mutations a male carries throughout his genome. Genetic variances and covariances, including the covariance between the preference and male trait that drives the good genes process, are allowed to evolve under an infinitesimal model. Results suggest that the good genes process generates only weak indirect selection on preferences, with an effective selection intensity of a few percent or less. If preferences are subject to direct natural selection of the intensity observed for other characters, the good genes process alone is not expected to exaggerate the male trait by more than a few phenotypic standard deviations, contrary to what is observed in highly sexually selected species. Good genes can, however, cause substantial exaggeration if preference genes are nearly selectively neutral. Alternatively, direct selection on preference genes, acting on mating behavior itself or on the genes' pleiotropic effects, can cause mating preferences and male display traits to be exaggerated by any degree. Direct selection of preference genes may therefore play an important role in species that show extreme sexual selection.     

Evolution of quantitative traits in the wild: mind the ecology

Recent advances in the quantitative genetics of traits in wild animal populations have created new interest in whether natural selection, and genetic response to it, can be detected within long-term ecological studies. However, such studies have re-emphasized the fact that ecological heterogeneity can confound our ability to infer selection on genetic variation and detect a population''s response to selection by conventional quantitative genetics approaches. Here, I highlight three manifestations of this issue: counter gradient variation, environmentally induced covariance between traits and the correlated effects of a fluctuating environment. These effects are symptomatic of the oversimplifications and strong assumptions of the breeder''s equation when it is applied to natural populations. In addition, methods to assay genetic change in quantitative traits have overestimated the precision with which change can be measured. In the future, a more conservative approach to inferring quantitative genetic response to selection, or genomic approaches allowing the estimation of selection intensity and responses to selection at known quantitative trait loci, will provide a more precise view of evolution in ecological time.     

Can natural selection favour altruism between species?

Darwin suggested that the discovery of altruism between species would annihilate his theory of natural selection. However, it has not been formally shown whether between‐species altruism can evolve by natural selection, or why this could never happen. Here, we develop a spatial population genetic model of two interacting species, showing that indiscriminate between species helping can be favoured by natural selection. We then ask if this helping behaviour constitutes altruism between species, using a linear‐regression analysis to separate the total action of natural selection into its direct and indirect (kin selected) components. We show that our model can be interpreted in two ways, as either altruism within species, or altruism between species. This ambiguity arises depending on whether or not we treat genes in the other species as predictors of an individual's fitness, which is equivalent to treating these individuals as agents (actors or recipients). Our formal analysis, which focuses upon evolutionary dynamics rather than agents and their agendas, cannot resolve which is the better approach. Nonetheless, because a within‐species altruism interpretation is always possible, our analysis supports Darwin's suggestion that natural selection does not favour traits that provide benefits exclusively to individuals of other species.     

Shrinking before our isles: the rapid expression of insular dwarfism in two invasive populations of guttural toad (Sclerophrys gutturalis)

Island ecosystems have traditionally been hailed as natural laboratories for examining phenotypic change, including dramatic shifts in body size. Similarly, biological invasions can drive rapid localized adaptations within modern timeframes. Here, we compare the morphology of two invasive guttural toad (Sclerophrys gutturalis) populations in Mauritius and Réunion with their source population from South Africa. We found that female toads on both islands were significantly smaller than mainland counterparts (33.9% and 25.9% reduction, respectively), as were males in Mauritius (22.4%). We also discovered a significant reduction in the relative hindlimb length of both sexes, on both islands, compared with mainland toads (ranging from 3.4 to 9.0%). If our findings are a result of natural selection, then this would suggest that the dramatic reshaping of an amphibian''s morphology—leading to insular dwarfism—can result in less than 100 years; however, further research is required to elucidate the mechanism driving this change (e.g. heritable adaptation, phenotypic plasticity, or an interaction between them).     

Joint phenotypes,evolutionary conflict and the fundamental theorem of natural selection

Multiple organisms can sometimes affect a common phenotype. For example, the portion of a leaf eaten by an insect is a joint phenotype of the plant and insect and the amount of food obtained by an offspring can be a joint trait with its mother. Here, I describe the evolution of joint phenotypes in quantitative genetic terms. A joint phenotype for multiple species evolves as the sum of additive genetic variances in each species, weighted by the selection on each species. Selective conflict between the interactants occurs when selection takes opposite signs on the joint phenotype. The mean fitness of a population changes not just through its own genetic variance but also through the genetic variance for its fitness that resides in other species, an update of Fisher''s fundamental theorem of natural selection. Some similar results, using inclusive fitness, apply to within-species interactions. The models provide a framework for understanding evolutionary conflicts at all levels.     

Functional divergence of a heterochromatin‐binding protein during stickleback speciation

Intragenomic conflict, the conflict of interest between different genomic regions within an individual, is proposed as a mechanism driving both the rapid evolution of heterochromatin‐related proteins and the establishment of intrinsic genomic incompatibility between species. Although molecular studies of laboratory model organisms have demonstrated the link between heterochromatin evolution and hybrid abnormalities, we know little about their link in natural systems. Previously, we showed that F₁ hybrids between the Japan Sea stickleback and the Pacific Ocean stickleback show hybrid male sterility and found a region responsible for hybrid male sterility on the X chromosome, but did not identify any candidate genes. In this study, we first screened for genes rapidly evolving under positive selection during the speciation of Japanese sticklebacks to find genes possibly involved in intragenomic conflict. We found that the region responsible for hybrid male sterility contains a rapidly evolving gene encoding a heterochromatin‐binding protein TRIM24B. We conducted biochemical experiments and showed that the binding affinity of TRIM24B to a heterochromatin mark found at centromeres and transposons, histone H4 lysine 20 trimethylation (H4K20me3), is reduced in the Japan Sea stickleback. In addition, mRNA expression levels of Trim24b were different between the Japan Sea and the Pacific Ocean testes. Further expression analysis of genes possibly in the TRIM24B‐regulated pathway showed that some gypsy retrotransposons are overexpressed in the F₁ hybrid testes. We, therefore, demonstrate that a heterochromatin‐binding protein can evolve rapidly under positive selection and functionally diverge during stickleback speciation.     

Genomic Imprinting As a Window into Human Language Evolution

Humans spend large portions of their time and energy talking to one another, yet it remains unclear whether this activity is primarily selfish or altruistic. Here, it is shown how parent‐of‐origin specific gene expression—or “genomic imprinting”—may provide an answer to this question. First, it is shown why, regarding language, only altruistic or selfish scenarios are expected. Second, it is pointed out that an individual's maternal‐origin and paternal‐origin genes may have different evolutionary interests regarding investment into language, and that this intragenomic conflict may drive genomic imprinting which—as the direction of imprint depends upon whether investment into language is relatively selfish or altruistic—may be used to discriminate between these two possibilities. Third, predictions concerning the impact of various mutations and epimutations at imprinted loci on language pathologies are derived. In doing so, a framework is developed that highlights avenues for using intragenomic conflicts to investigate the evolutionary drivers of language.     

Genetic composition of social groups influences male aggressive behaviour and fitness in natural genotypes of Drosophila melanogaster

Indirect genetic effects (IGEs) describe how an individual''s behaviour—which is influenced by his or her genotype—can affect the behaviours of interacting individuals. IGE research has focused on dyads. However, insights from social networks research, and other studies of group behaviour, suggest that dyadic interactions are affected by the behaviour of other individuals in the group. To extend IGE inferences to groups of three or more, IGEs must be considered from a group perspective. Here, I introduce the ‘focal interaction’ approach to study IGEs in groups. I illustrate the utility of this approach by studying aggression among natural genotypes of Drosophila melanogaster. I chose two natural genotypes as ‘focal interactants’: the behavioural interaction between them was the ‘focal interaction’. One male from each focal interactant genotype was present in every group, and I varied the genotype of the third male—the ‘treatment male’. Genetic variation in the treatment male''s aggressive behaviour influenced the focal interaction, demonstrating that IGEs in groups are not a straightforward extension of IGEs measured in dyads. Further, the focal interaction influenced male mating success, illustrating the role of IGEs in behavioural evolution. These results represent the first manipulative evidence for IGEs at the group level.     

The evolution of harm--effect of sexual conflicts and population size

Conflicts of interest between mates can promote the evolution of male traits that reduce female fitness and that drive coevolution between the sexes. The rate of adaptation depends on the intensity of selection and its efficiency, which depends on drift and genetic variability. This leads to the largely untested prediction that coevolutionary adaptations such as those driven by sexual conflict should evolve faster in large populations. We tested this using the bruchid beetle Callosobruchus maculatus, a species where harm inflicted by males is well documented. Although most experimental evolution studies remove sexual conflict, we reintroduced it in populations in which it had been experimentally removed. Both population size and standing genetic variability were manipulated in a factorial experimental design. After 90 generations of relaxed conflict (monogamy), the reintroduction of sexual conflicts for 30 generations favored males that harmed females and females that were more resistant to the genital damage inflicted by males. Males evolved to become more harmful when population size was large rather than when initial genetic variation was enriched. Our study shows that sexual selection can create conditions in which males can benefit from harming females and that selection may tend to be more intense and effective in larger populations.