What do we mean by G ^ E interdependence? As is traditionally thought, the environment influences the genes, but the idea of interdependence also incorporates the newer idea that the effects of the environment may result from an indirect consequence of the animal's genotype. For example, animals with certain genotypes may have an increased probability of choosing a particular habitat, and this habitat choice can have consequences for the animals' subsequent pattern of gene expression. Indeed there may be long-term consequences for the frequency of the alleles that facilitated a specific habitat preference. More specifically, individuals with alleles that predispose them to take risks are therefore more likely to encounter risky situations.

This can result in reward or punishment which affects the subsequent gene expression and behaviour of the risk takers, and which also has long-term fitness consequences. G ^ E interdependencies are most common in the case of social interactions, because the social environment produces large effects on individual behaviour with consequences that can, say, through stress, alter an individual's gene expression. Thus, social behaviour is a special case of G ^ E interdependence because conspecif-ics represent an environmental factor that can then change the organisms' gene expression and subsequent behaviours (see also Chapter 2). As is the case with habitat selection and risk taking, organisms can choose social situations. From this perspective, social context can be considered to be an environmental factor.

1.4 Different kinds of environments

The previous sections illustrate that GxE interactions capture - more or less - the relationship between a phenotype and its genetic substrate. The emphasis on G x E interaction is an analytical advance over G + E. The interaction term recognises that the response of a genotype may vary across environments in a complex manner. This analysis is further refined by considering what is meant by 'environment'.

As described above, the term environment can refer to abiotic factors (temperature, humidity) and biotic factors (density of individuals, social groupings, parenting). Increasingly, the social environment is considered an important influence on an individual's gene expression and behaviour (see Chapters 10, 11 and 18). As discussed below, an individual's experience of social interactions may affect reproductive success. This establishes an interesting feedback loop whereby the group influences individual group members in a manner that tweaks the population of genes and alleles across generations. This idea is not new: a relationship between social life and the genetic landscape was articulated by the ecologist W. C. Allee in the early part of the last century. Allee suggested that life in groups is adaptive - within limits. He linked his own observations on the phylogeny of social life to Sewall Wright's quantitative theories of population genetics (Allee 1958). Recently, Allen Moore and colleagues (Moore et al. 1997, Wolf et al. 1998; Chapter 2) have reintroduced the idea that there is something special about the social environment. They proposed a theory of indirect genetic effects (IGE). Broadly put, this theory states that social experience shapes phenotypic variability and thereby influences the frequency of alleles in a population. According to this view, an individual's phenotype is a function of genotype, physical environment and social environment. The quantitative statement of the theory is remarkable because it is written in terms of how an individual is affected by his or her social experience and because, in principle, the effects of genotype and at least two types of environment (physical and social) may be quantified. Partitioning the environmental variable into physical and social parts is an essential feature of the theory.

Several studies have demonstrated indirect genetic effects. For example, in their studies on display traits in wild caught Drosophila serrata, Blows and colleagues have shown that individual flies, males and females, adjust the expression of pheromonal signals in accord with their social environment (Petfield et al. 2005; see also Wolf et al. 1999, 2002, 2003, Wolf 2000). Moreover, Krupp et al. (2008) have demonstrated that the composition of a social group influences patterns of gene expression and pheromonal signalling as well as levels of mating in D. melanogaster. Consistent with the theoretical ideas noted in the previous paragraph, this study demonstrates that the frequency of copulation increases with increasing genotypic diversity among males in a social group (Krupp et al. 2008). In a related study, Kent et al. (2008) found significant G x S (S is the social environment) interactions for nearly all of the chemical signals found on the surface of male D. melanogaster. In some cases the G x S interaction factor accounted for more variability than others in the model (Kent et al. 2008). Kent et al. also show quantitatively that male flies exert indirect genetic effects on other males. In these experiments, individual pheromonal displays are predicted by the genotypic composition of a social group. This demonstration of social effects on individual behaviours is especially salient because studies that take molecular and cellular approaches to understanding a phe-notype tend to be framed around individual subjects (e.g. how does the individual smell or learn or court or eat?). In this respect, the theory of indirect genetic effects may provide a bridge between quantitative genetics and molecular genetics, as demonstrated by the studies of Krupp et al. and Kent et al.; it is all the more noteworthy that this bridge depends on the important role of the social environment.

Although not usually studied within the theoretical framework associated with IGE and quantitative genetics, an influence of the social environment on individual development defines another important class of effects. Eusocial insects, such as the honey bee Apis mellifera, are known to maintain a highly structured social environment, but even for eusocial insects there is some plasticity associated with the division of labour in the hive (Robinson 2004, Robinson et al. 2005). This is evident based on developmental, molecular, and behavioural criteria. Indeed, the social role of a honey bee within the hive is a complex trait that may be determined in part by social density. Ordinarily, nurses become foragers when they are about three weeks old. A marker for this new job is the onset of a functional circadian clock mechanism in the brain. Prior to assuming the role of a forager, clock genes, such as period, are expressed but not in a pattern that is consistent with a timing function. Once the transition from nurse to forager occurs, levels of period transcription oscillate throughout the day, a signature feature of circadian clock function. However, when caste ratios within the hive are manipulated to leave mostly young nurses with a shortage of foragers, some of the nurses undergo a precocious development of circadian function and make an early transition to become foragers (Bloch et al. 2001, Bloch & Robinson 2001). These remarkable studies show that a change in the social environment induces precocious changes in gene expression in some individuals. The interaction between social environment and gene expression can alter development and social role even within the rigid context of a beehive.

In general, studies within the framework of indirect genetic effects and in eusocial insects support the idea that the social environment plays an important role in shaping the relationship between phenotype and genotype. We have described examples related to courtship and foraging behaviours. The example from the bees points towards the theme of development. From a biological standpoint many adult behavioural phenotypes require developmental forerunners (Ganguly-Fitzgerald et al, 2006), just as the nurse-forager transition requires that all the components needed for a functional circadian clock are ready. In the next section, we address the role of development per se.

1.5 Development

Previous sections have emphasised ideas and methods from quantitative genetics as a framework for understanding the relationship between phenotype and genotype. Early development is a time when interactions between the environment and genotype may be critical for establishing the mature individual in terms of physiology and behaviour. Although, in statistical terms, an emphasis on development is not consistent with the analytic framework we have been presenting (development is not independent of genes and environment), it is noteworthy because of its special role in many behavioural phenotypes.

The timing of environmental input is critical for the development and performance of individual differences in behaviour. In some cases critical periods have been reported for normal behavioural development. A 'critical period' is a time in the development of an organism when it shows a heightened sensitivity to particular environmental stimuli. The organism's development is altered due to its experiences during the critical period. If the organism does not get the appropriate stimuli during the critical period, its development, behaviour and health may be compromised later in life (Hensch 2005).

Research on both humans and rhesus monkeys Macaca mulatta shows persuasive evidence for specific G x E interactions framed by a critical period in development. In general, the short-allele polymorphism in the promoter region of the serotonin transporter gene is associated with poor neuronal function in infancy and poor control of aggression in the juvenile and adolescent stages of development when monkeys are reared in infancy with peers but no mothers. Monkeys with the short allele raised during this period of development with their mothers and their peers did not exhibit these deficiencies. And finally, monkeys with the long allele are normal for all of these factors regardless of their early social rearing (Suomi 2006).

Like genes, environmental factors can affect the development and/or functioning of behaviour. The gene's product may be required during development, for example, to construct a nervous system that facilitates the later performance of a behaviour pattern. Alternatively, the gene's product may only be required to function during the performance of the behaviour pattern. Another possibility is that the gene's product may be involved in both developmental and functional aspects of the behavioural phenotype. This can be assessed using genetic tools, such as transgen-ics, to express or turn off gene expression at different times during development and adulthood. Molecular techniques can be applied to resolve details of genetic contributions to behaviour.

The importance of development, of maternal and other social input and of certain sensory stimuli during critical periods of development is well established for a diverse array of animals including insects, rodents and primates. The ease with which we might slip into the language of 'nature-nurture' dichotomies may be partly due to the powerful influence of the maternal nurturing that is thought to be so important for human development. It is therefore noteworthy that recent developments in the study of mothering suggest that there are mechanisms of inheritance that may not be determined by the genome, which we now discuss.

1.6 Epigenetic changes as an interface between nature and nurture

A new level of complexity in the evaluation of inheritance has appeared within the last decade. Epigenetics introduces a wrinkle into the relationship between phenotype and genotype because this source of inheritance does not depend directly on genomic sequence. Instead, epigenetics emphasises the relationship between phenotype and environment; this mechanism feeds back to regulate gene expression without altering the genotype. This view is especially compelling because one of the best examples of an epigenetic effect relates to a paradigm of social behaviour, the maternal influence on stress response.

Bird (2007) defines epigenetic events as 'the structural adaptation of chromosomal regions so as to register, signal, or perpetuate altered activity states.' In a seminal review, he goes on to write that 'epigenetic processes are buffers of genetic variation, pending a change of state that leads an identical combination of genes to produce a different developmental outcome.' This definition includes the use of the term in developmental biology as well as in behavioural studies, and it declares that an epigenetic event is a response.

Szyf, Meaney and colleagues have characterised an epigenetic mechanism for determining stress responses in rats. They call it maternal programming (Weaver etal. 2004,2005, Szyf etal. 2005). The response to stress is mediated by glucocorticoid receptors in the hippocampus. Levels of glucocorticoid receptors are affected by licking and grooming provided by mothers during the first week of life. Offspring of mothers that lick and groom at high levels produce higher number of copies of glucocorticoid receptor mRNA, while offspring that receive less licking and grooming make fewer copies. In addition, the offspring of mothers with higher levels of licking and grooming show increased hippocampal receptor sensitivity, increased sensitivity to steroid feedback, decreased hypothalamic levels of corticotrophin releasing factor, and decreased startle responses compared to offspring that received less maternal stimulation. In general, individuals that received higher maternal stimulation were less reactive to stressful stimuli, based on a variety of behavioural, neural and neuroendocrine measures.

Two critical observations call attention to this work. First, the expression of the glucocorticoid receptor is influenced by patterns of DNA methylation within the gene that encodes the receptor. DNA methylation is a type of chemical modification of the DNA that does not change the original DNA sequence. In this case the promoter of the glucocorticoid receptor is methylated (a methyl group is added), resulting in a decrease in the expression of this gene. These patterns are established by the level of licking and grooming received by the pup. The patterns are maintained into later stages of life, and they can be manipulated to alter responses to stressful stimuli based on experience. Thus the changes in gene activity in response to stress are controlled by patterns of methylation that define an epigenetic response to mothering. Second, the stress response-related effects of maternal licking and grooming are passed on to female offspring. The female offspring treat their offspring according to how they themselves were reared (with high or low levels of licking and grooming). Szyf et al. (2005) describe evidence that the transmission of this maternal behaviour across generations is related to methylation of the oestrogen receptor gene passed from mother to daughter.

Although there are not yet many examples of robust epigenetic effects on behaviour, the example of maternal behaviour in rats implies a level of complexity that is greater than G x E interactions. If such epigenetic effects prove to be common, then the inheritance of a phenotype must account for several tiers of plasticity both within the genome and 'around' it.

1.7 Conclusions and future directions

The relationship between phenotype and genotype is an ongoing matter of study. Traditionally, behavioural studies have oscillated between the ideas that behaviour may be determined more by the genes than the environment or vice versa. However, this 'nature-nurture' dichotomy has proved false. Statistical approaches associated with quantitative genetics have shown that including interaction terms between genotype and environment (G x E) is more realistic than a restricted additive view (G + E).

The concepts associated with G x E interactions have been expanding. One such expansion has to do with the interdependence of genes and the environment. Moreover, the environment itself may be partitioned into abiotic and biotic factors. A compelling example of this approach is illustrated by the theory of indirect genetic effects (IGE). This theory quantifies the influence of genotype, physical environment and social environment on an individual's phenotype. While calling attention to the importance of the social milieu, IGE provides a conceptual bridge between quantitative effects and the analysis of how specific genes contribute to an individual's phenotype; it implies that a molecular substrate for social experience can be described experimentally, and such examples are beginning to appear (Krupp et al. 2008, Kent etal. 2008).

Although developmental processes lie outside current quantitative frameworks, recent studies in monkeys and humans have suggested the profound importance of critical periods for social function and the development of behavioural responses in general. It is tempting to link developmental input to a role for epigenetic mechanisms that may underlie the inheritance of behavioural phenotypes. Studies on maternal care in rodents have shown that licking and grooming provided by a mother to her offspring within the first week after birth influences stress responses in the offspring once they mature. In addition, some qualities of the maternal behaviour style (high licking and grooming versus low) are transmitted from mother to daughter. These effects of maternal 'programming' are associated with methylation of DNA sequences that in turn affect the transcription of steroid receptors in the brain. Such epigenetic effects may represent a new level of analysis that mediates the relationship between genes and behaviour.

Throughout this chapter we have endeavoured to emphasise the importance of social context and social experience as an environmental stimulus that affects gene expression in individuals and, thus, phenotypic variability within a population. We emphasise new approaches and technologies that advance our understanding of the relationships between genes and environment and how they affect behaviour. These newer approaches expand our knowledge from quantitative genetic analyses to include an understanding of the molecular genetic mechanisms underlying behavioural variation. In the past, these quantitative genetic analyses were the only good approach to questions of gene-environment relationships, because we had little to no knowledge of the genes and genomes of most animals. However, in just a few years we will be able to obtain the complete DNA sequence of any animal's genome for under $1000! And knowledge of these sequences will enable us to measure changes in the expression of all genes in the genomes of any species with different social behaviours and in ecologically relevant environments. For example, we will be able to test hypotheses about suites of genes and pathways that are up- or downregulated in response to a social situation, and ask why. These findings could then be compared between individuals, populations and species to further frame our evolutionary hypotheses.

This integration requires interdisciplinary approaches and dialogue between those of us in different subfields. Initially, we may have to make simplifying assumptions about social groups in order to investigate molecular mechanisms that underlie social influences on perception, physiology and behaviour. We may have to relax ideas about examining social interactions at all life-history stages in ecological contexts. Once some of the mechanisms underlying the gene-environment relationships in social behaviour are understood then follow-up experiments can be done to include more complex social manipulations in ecologically relevant contexts. The examples we have presented in this chapter focus attention on genes and genomes. As more details become available, the critical tissues and developmental stages will become known. In this way, we will be able to carry the questions we have been asking from the level of genes and environment to fill in other levels. For example, neural, endocrine, muscular and metabolic systems may all be important contributors to variation in social behaviour and may have evolved in interesting ways - yet to be determined. Finally, technologies associated with high-throughput molecular methods and approaches from systems biology are advancing with great rapidity. It is likely that industrial-scale analyses (the -omics) of questions about social life and G x E interactions will be possible for many organisms in the near future. Exciting times are ahead.


We thank Dr Craig Riedl for advice and comments on the writing of this chapter, as well as two anonymous reviewers who provided valuable comments that improved the manuscript. Christie DesRoches helped with the preparation of the figures. JDL and MBS are supported by the Natural Science and Engineering Council of Canada and the Canada Research Chairs Programme.

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