Linking genotypes to phenotypes and fitness: how mechanistic biology can inform molecular ecology

The accessibility of new genomic resources, high‐throughput molecular technologies and analytical approaches such as genome scans have made finding genes contributing to fitness variation in natural populations an increasingly feasible task. Once candidate genes are identified, we argue that it is necessary to take a mechanistic approach and work up through the levels of biological organization to fully understand the impacts of genetic variation at these candidate genes. We demonstrate how this approach provides testable hypotheses about the causal links among levels of biological organization, and assists in designing relevant experiments to test the effects of genetic variation on phenotype, whole‐organism performance capabilities and fitness. We review some of the research programs that have incorporated mechanistic approaches when examining naturally occurring genetic and phenotypic variation and use these examples to highlight the value of developing a comprehensive understanding of the relationship between genotype and fitness. We give suggestions to guide future research aimed at uncovering and understanding the genetic basis of adaptation and argue that further integration of mechanistic approaches will help molecular ecologists better understand the evolution of natural populations.     

The causal structure of mechanisms

Recently, a number of philosophers of science have claimed that much explanation in the sciences, especially in the biomedical and social sciences, is mechanistic explanation. I argue the account of mechanistic explanation provided in this tradition has not been entirely satisfactory, as it has neglected to describe in complete detail the crucial causal structure of mechanistic explanation. I show how the interventionist approach to causation, especially within a structural equations framework, provides a simple and elegant account of the causal structure of mechanisms. This account explains the many useful insights of traditional accounts of mechanism, such as Carl Craver’s account in his book Explaining the Brain (2007), but also helps to correct the omissions of such accounts. One of these omissions is the failure to provide an explicit formulation of a modularity constraint that plays a significant role in mechanistic explanation. One virtue of the interventionist/structural equations framework is that it allows for a simple formulation of a modularity constraint on mechanistic explanation. I illustrate the role of this constraint in the last section of the paper, which describes the form that mechanistic explanation takes in the computational, information-processing paradigm of cognitive psychology.     

Cooperation for direct fitness benefits

Studies of the evolution of helping have traditionally used the explanatory frameworks of reciprocity and altruism towards relatives, but recently there has been an increasing interest in other kinds of explanations. We review the success or otherwise of work investigating alternative processes and mechanisms, most of which fall under the heading of cooperation for direct benefits. We evaluate to what extent concepts such as by-product benefits, pseudo-reciprocity, sanctions and partner choice, markets and the build-up of cross-species spatial trait correlations have contributed to the study of the evolution of cooperation. We conclude that these alternative ideas are successful and show potential to further increase our understanding of cooperation. We also bring up the origin and role of common interest in the evolution of cooperation, including the appearance of organisms. We note that there are still unresolved questions about the main processes contributing to the evolution of common interest. Commenting on the broader significance of the recent developments, we argue that they represent a justified balancing of the importance given to different major hypotheses for the evolution of cooperation. This balancing is beneficial because it widens considerably the range of phenomena addressed and, crucially, encourages empirical testing of important theoretical alternatives.     

Using reaction mechanism to measure enzyme similarity

The concept of reaction similarity has been well studied in terms of the overall transformation associated with a reaction, but not in terms of mechanism. We present the first method to give a quantitative measure of the similarity of reactions based upon their explicit mechanisms. Two approaches are presented to measure the similarity between individual steps of mechanisms: a fingerprint-based approach that incorporates relevant information on each mechanistic step; and an approach based only on bond formation, cleavage and changes in order. The overall similarity for two reaction mechanisms is then calculated using the Needleman-Wunsch alignment algorithm. An analysis of MACiE, a database of enzyme mechanisms, using our measure of similarity identifies some examples of convergent evolution of chemical mechanisms. In many cases, mechanism similarity is not reflected by similarity according to the EC system of enzyme classification. In particular, little mechanistic information is conveyed by the class level of the EC system.     

The cultural evolution of fertility decline

Cultural evolutionists have long been interested in the problem of why fertility declines as populations develop. By outlining plausible mechanistic links between individual decision-making, information flow in populations and competition between groups, models of cultural evolution offer a novel and powerful approach for integrating multiple levels of explanation of fertility transitions. However, only a modest number of models have been published. Their assumptions often differ from those in other evolutionary approaches to social behaviour, but their empirical predictions are often similar. Here I offer the first overview of cultural evolutionary research on demographic transition, critically compare it with approaches taken by other evolutionary researchers, identify gaps and overlaps, and highlight parallel debates in demography. I suggest that researchers divide their labour between three distinct phases of fertility decline—the origin, spread and maintenance of low fertility—each of which may be driven by different causal processes, at different scales, requiring different theoretical and empirical tools. A comparative, multi-level and mechanistic framework is essential for elucidating both the evolved aspects of our psychology that govern reproductive decision-making, and the social, ecological and cultural contingencies that precipitate and sustain fertility decline.     

A new, vapour-phase mechanism for stomatal responses to humidity and temperature

A new mechanism for stomatal responses to humidity and temperature is proposed. Unlike previously-proposed mechanisms, which rely on liquid water transport to create water potential gradients within the leaf, the new mechanism assumes that water transport to the guard cells is primarily through the vapour phase. Under steady-state conditions, guard cells are assumed to be in near-equilibrium with the water vapour in the air near the bottom of the stomatal pore. As the water potential of this air varies with changing air humidity and leaf temperature, the resultant changes in guard cell water potential produce stomatal movements. A simple, closed-form, mathematical model based on this idea is derived. The new model is parameterized for a previously published set of data and is shown to fit the data as well as or better than existing models. The model contains mathematical elements that are consistent with previously-proposed mechanistic models based on liquid flow as well as empirical models based on relative humidity. As such, it provides a mechanistic explanation for the realm of validity for each of these approaches.     

The concept of mechanism in biology

The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology ('mechanicism'), to the internal workings of a machine-like structure ('machine mechanism'), or to the causal explanation of a particular phenomenon ('causal mechanism'). In this paper I trace the conceptual evolution of 'mechanism' in the history of biology, and I examine how the three meanings of this term have come to be featured in the philosophy of biology, situating the new 'mechanismic program' in this context. I argue that the leading advocates of the mechanismic program (i.e., Craver, Darden, Bechtel, etc.) inadvertently conflate the different senses of 'mechanism'. Specifically, they all inappropriately endow causal mechanisms with the ontic status of machine mechanisms, and this invariably results in problematic accounts of the role played by mechanism-talk in scientific practice. I suggest that for effective analyses of the concept of mechanism, causal mechanisms need to be distinguished from machine mechanisms, and the new mechanismic program in the philosophy of biology needs to be demarcated from the traditional concerns of mechanistic biology.     

Two ways to use imaging: focusing directly on mechanism, or indirectly via behaviour?

Recent developments in mesoscopic imaging--imaging at the level of tissues and organs, rather than the subcellular or molecular scale--are proving to be powerful for developmental biology. At the same time, these developments are also helping to emphasize an important distinction between two quite different approaches of how imaging is used. In the more traditional approach, images provide a direct insight into how a systems works-suggesting a mechanism or part of a mechanism. However an alternative approach is gaining ground, in which imaging is used to quantify the behaviour of a system, rather than directly assessing the mechanism. In this case the causal relationships of a system are inferred in a more indirect way-by comparing quantitative measurements with mathematical models of the system in question. Although indirect, this approach is powerful for addressing more complex biological systems--especially multiscale problems. It is tempting to distinguish the latter approach with the label 'quantitative biology', but this term only emphasizes the use of numbers, and therefore obscures the more fundamental difference, which is the powerful but indirect nature of the approach. Here I will discuss the distinction between the two imaging approaches, particularly in the context of recent improvements to tissue-level imaging techniques.     

Causal mechanisms of evolution and the capacity for niche construction

Ernst Mayr proposed a distinction between “proximate”, mechanistic, and “ultimate”, evolutionary, causes of biological phenomena. This dichotomy has influenced the thinking of many biologists, but it is increasingly perceived as impeding modern studies of evolutionary processes, including study of “niche construction” in which organisms alter their environments in ways supportive of their evolutionary success. Some still find value for this dichotomy in its separation of answers to “how?” versus “why?”questions about evolution. But “why is A?” questions about evolution necessarily take the form “how does A occur?”, so this separation is illusory. Moreover, the dichotomy distorts our view of evolutionary causality, in that, contra Mayr, the action of natural selection, driven by genotype-phenotype-environment interactions which constitute adaptations, is no less “proximate” than the biological mechanisms which are altered by naturally selected genetic variants. Mayr’s dichotomy thus needs replacement by more realistic, mechanistic views of evolution. From a mechanistic viewpoint, there is a continuum of adaptations from those evolving as responses to unchanging environmental pressures to those evolving as the capacity for niche construction, and intermediate stages of this can be identified. Some biologists postulate an association of “phenotypic plasticity” (phenotype-environment covariation with genotype held constant) with capacity for niche construction. Both “plasticity” and niche construction comprise wide ranges of adaptive mechanisms, often fully heritable and resulting from case-specific evolution. Association of “plasticity” with niche construction is most likely to arise in systems wherein capacity for complex learning and behavioral flexibility have already evolved.     

The cost of reproduction: the devil in the details

The cost of reproduction is of fundamental importance in life-history evolution. However, our understanding of its mechanistic basis has been limited by a lack of detailed functional information at all biological levels. Here, we identify, evaluate and integrate recent studies in five areas examining the proximate mechanisms underlying the cost of reproduction. Rather than being alternate explanations, hormonal regulation and intermediary metabolism act in concert and have an overarching influence in shaping the cost of reproduction. Immune function is compromised by reproduction, as is resistance to environmental stress. These studies not only provide new information about mechanisms that comprise 'the cost', but also hint at an underlying evolutionarily conserved causal mechanism.     

The importance of mechanisms for the evolution of cooperation

Studies aimed at explaining the evolution of phenotypic traits have often solely focused on fitness considerations, ignoring underlying mechanisms. In recent years, there has been an increasing call for integrating mechanistic perspectives in evolutionary considerations, but it is not clear whether and how mechanisms affect the course and outcome of evolution. To study this, we compare four mechanistic implementations of two well-studied models for the evolution of cooperation, the Iterated Prisoner''s Dilemma (IPD) game and the Iterated Snowdrift (ISD) game. Behavioural strategies are either implemented by a 1 : 1 genotype–phenotype mapping or by a simple neural network. Moreover, we consider two different scenarios for the effect of mutations. The same set of strategies is feasible in all four implementations, but the probability that a given strategy arises owing to mutation is largely dependent on the behavioural and genetic architecture. Our individual-based simulations show that this has major implications for the evolutionary outcome. In the ISD, different evolutionarily stable strategies are predominant in the four implementations, while in the IPD each implementation creates a characteristic dynamical pattern. As a consequence, the evolved average level of cooperation is also strongly dependent on the underlying mechanism. We argue that our findings are of general relevance for the evolution of social behaviour, pleading for the integration of a mechanistic perspective in models of social evolution.     

Causation at different levels: tracking the commitments of mechanistic explanations

This paper tracks the commitments of mechanistic explanations focusing on the relation between activities at different levels. It is pointed out that the mechanistic approach is inherently committed to identifying causal connections at higher levels with causal connections at lower levels. For the mechanistic approach to succeed a mechanism as a whole must do the very same thing what its parts organised in a particular way do. The mechanistic approach must also utilise bridge principles connecting different causal terms of different theoretical vocabularies in order to make the identities of causal connections transparent. These general commitments get confronted with two claims made by certain proponents of the mechanistic approach: William Bechtel often argues that within the mechanistic framework it is possible to balance between reducing higher levels and maintaining their autonomy at the same time, whereas, in a recent paper, Craver and Bechtel argue that the mechanistic approach is able to make downward causation intelligible. The paper concludes that the mechanistic approach imbued with identity statements is no better candidate for anchoring higher levels to lower ones while maintaining their autonomy at the same time than standard reductive accounts are, and that what mechanistic explanations are able to do at best is showing that downward causation does not exist.     

Sex,long life and the evolutionary transition to cooperative breeding in birds

Long life is a typical feature of individuals living in cooperative societies. One explanation is that group living lowers mortality, which selects for longer life. Alternatively, long life may make the evolution of cooperation more likely by ensuring a long breeding tenure, making helping behaviour and queuing for breeding positions worthwhile. The benefit of queuing will, however, depend on whether individuals gain indirect fitness benefits while helping, which is determined by female promiscuity. Where promiscuity is high and therefore the indirect fitness benefits of helping are low, cooperation can still be favoured by an even longer life span. We present the results of comparative analyses designed to test the likelihood of a causal relationship between longevity and cooperative breeding by reconstructing ancestral states of cooperative breeding across birds, and by examining the effect of female promiscuity on the relationship between these two traits. We found that long life makes the evolution of cooperation more likely and that promiscuous cooperative species are exceptionally long lived. These results make sense of promiscuity in cooperative breeders and clarify the importance of life-history traits in the evolution of cooperative breeding, illustrating that cooperation can evolve via the combination of indirect and direct fitness benefits.     

Models of social evolution: can we do better to predict ‘who helps whom to achieve what’?

Models of social evolution and the evolution of helping have been classified in numerous ways. Two categorical differences have, however, escaped attention in the field. Models tend not to justify why they use a particular assumption structure about who helps whom: a large number of authors model peer-to-peer cooperation of essentially identical individuals, probably for reasons of mathematical convenience; others are inspired by particular cooperatively breeding species, and tend to assume unidirectional help where subordinates help a dominant breed more efficiently. Choices regarding what the help achieves (i.e. which life-history trait of the helped individual is improved) are similarly made without much comment: fecundity benefits are much more commonly modelled than survival enhancements, despite evidence that these may interact when the helped individual can perform life-history reallocations (load-lightening and related phenomena). We review our current theoretical understanding of effects revealed when explicitly asking ‘who helps whom to achieve what’, from models of mutual aid in partnerships to the very few models that explicitly contrast the strength of selection to help enhance another individual''s fecundity or survival. As a result of idiosyncratic modelling choices in contemporary literature, including the varying degree to which demographic consequences are made explicit, there is surprisingly little agreement on what types of help are predicted to evolve most easily. We outline promising future directions to fill this gap.     

Psychological adaptations for assessing gossip veracity

Evolutionary models of human cooperation are increasingly emphasizing the role of reputation and the requisite truthful “gossiping” about reputation-relevant behavior. If resources were allocated among individuals according to their reputations, competition for resources via competition for “good” reputations would have created incentives for exaggerated or deceptive gossip about oneself and one’s competitors in ancestral societies. Correspondingly, humans should have psychological adaptations to assess gossip veracity. Using social psychological methods, we explored cues of gossip veracity in four experiments. We found that simple reiteration increased gossip veracity, but only for those who found the gossip relatively uninteresting. Multiple sources of gossip increased its veracity, as did the independence of those sources. Information that suggested alternative, benign interpretations of gossip decreased its veracity. Competition between a gossiper and her target decreased gossip veracity. These results provide preliminary evidence for psychological adaptations for assessing gossip veracity, mechanisms that might be used to assess veracity in other domains involving social exchange of information.     

New thinking, innateness and inherited representation

The New Thinking contained in this volume rejects an Evolutionary Psychology that is committed to innate domain-specific psychological mechanisms: gene-based adaptations that are unlearnt, developmentally fixed and culturally universal. But the New Thinking does not simply deny the importance of innate psychological traits. The problem runs deeper: the concept of innateness is not suited to distinguishing between the New Thinking and Evolutionary Psychology. That points to a more serious problem with the concept of innateness as it is applied to human psychological phenotypes. This paper argues that the features of recent human evolution highlighted by the New Thinking imply that the concept of inherited representation, set out here, is a better tool for theorizing about human cognitive evolution.     

Psychological essentialism from first principles

Cognitive scientists have documented the existence of “essentialist” intuitions in humans: from a very early age, we assume that things have deep unobserved properties that make them what they are. I provide a sketch of an adaptationist explanation of psychological essentialism, arguing that these intuitions are the unsurprising output of adaptations for inductive inference. Variations on this insight have previously been used mostly as after-the-fact speculations, yet theories of adaptive function should ideally have a primary role in informing psychological research. Here I propose that viewing essentialist intuitions through an adaptationist lens has implications for some widespread assumptions about the phenomenon. Notably, researchers' focus on “higher-level” processes like categorization has led them to assume that essentialism is restricted to a few cognitive processes, but the ubiquity of inductive inference problems in cognition suggests otherwise. Additionally, because essentialist intuitions are the output of mechanisms solving related but distinct inference problems, it is unlikely that a single mechanistic theory can account for them all.     

The power of possibility: causal learning, counterfactual reasoning, and pretend play

We argue for a theoretical link between the development of an extended period of immaturity in human evolution and the emergence of powerful and wide-ranging causal learning mechanisms, specifically the use of causal models and Bayesian learning. We suggest that exploratory childhood learning, childhood play in particular, and causal cognition are closely connected. We report an empirical study demonstrating one such connection--a link between pretend play and counterfactual causal reasoning. Preschool children given new information about a causal system made very similar inferences both when they considered counterfactuals about the system and when they engaged in pretend play about it. Counterfactual cognition and causally coherent pretence were also significantly correlated even when age, general cognitive development and executive function were controlled for. These findings link a distinctive human form of childhood play and an equally distinctive human form of causal inference. We speculate that, during human evolution, computations that were initially reserved for solving particularly important ecological problems came to be used much more widely and extensively during the long period of protected immaturity.