Marla B. Sokolowski

Drosophila : Genetics meets behaviour

Genes are understandably crucial to physiology, morphology and biochemistry, but the idea of genes contributing to individual differences in behaviour once seemed outrageous. Nevertheless, some scientists have aspired to understand the relationship between genes and behaviour, and their research has become increasingly informative and productive over the past several decades. At the forefront of behavioural genetics research is the fruitfly Drosophila melanogaster, which has provided us with important insights into the molecular, cellular and evolutionary bases of behaviour.

Foraging Strategies of Drosophila melanogaster: A Chromosomal Analysis

Two larval foraging strategies inDrosophila melanogaster were identified, “rover” and “sitter.” “Rovers” traverse a large area while feeding whereas “sitters” cover a small area. The difference between “rovers” and “sitters” was analyzed genetically by chromosomal substitutions between isogenic stocks. Differences in larval locomotor behavior (“crawling behavior”) can be attributed to the second chromosome, the “rover” strategy being dominant over the “sitter” strategy. Differences in feeding rate (“shoveling behavior”) are affected additively by both the second and third chromosomes. Natural populations ofDrosophila larvae were sampled three times over a 2-month period; “rovers” and “sitters” were at constant frequencies in these populations. The two foraging strategies are discussed in the light of resource utilization in environments where food is distributed continuously or discontinuously.

cGMP-dependent changes in phototaxis: a possible role for the foraging gene in honey bee division of labor

SUMMARY Division of labor in honey bee colonies is influenced by the foraging gene (Amfor), which encodes a cGMP-dependent protein kinase (PKG). Amfor upregulation in the bee brain is associated with the age-related transition from working in the hive to foraging for food outside, and cGMP treatment (which increases PKG activity) causes precocious foraging. We present two lines of evidence in support of the hypothesis that Amfor affects division of labor by modulating phototaxis. We first show that a subset of worker bees involved in the removal of corpses from the hive had forager-like brain levels of Amfor brain expression despite being middle aged; age-matched food-handlers, who do not leave the hive to perform their job, had low levels of Amfor expression. This finding suggests that occupations that involve working outside the hive are associated with high levels of Amfor in brain. Secondly, foragers were much more positively phototactic than hive bees in a laboratory assay, and cGMP treatment caused a precocious onset of positive phototaxis. The cGMP effect was not due to a general increase in behavioral activity; cGMP treatment had no effect on locomotor activity under either constant darkness or a light:dark regime. The cGMP effect also was not due to changes in circadian rhythmicity; cGMP treatment had no effect on age at onset of locomotor circadian rhythmicity or the period of rhythmicity. The effects of Amfor on phototaxis are not related to peripheral processing; electroretinogram analysis revealed no effect of cGMP treatment on photoreceptor activity and no differences between untreated hive bees and foragers. The cAMP/PKA pathway does not appear to be playing a similar role to cGMP/PKG in the honey bee; cAMP treatment did not affect phototaxis and gene expression analysis revealed task-related differences only for the gene encoding the regulatory subunit, but not the catalytic subunit, of PKA. Our findings implicate one neural process associated with honey bee division of labor that can be affected by naturally occurring changes in the expression of Amfor.

Maintaining a behaviour polymorphism by frequency-dependent selection on a single gene.

Accounting for the abundance of genetic variation in the face of natural selection remains a central problem of evolutionary biology. Genetic polymorphisms are constantly arising through mutation, and although most are promptly eliminated, polymorphisms in functionally important traits are common. One mechanism that can maintain polymorphisms is negative frequency-dependent selection on alternative alleles, whereby the fitness of each decreases as its frequency increases. Examples of frequency-dependent selection are rare, especially when attempting to describe the genetic basis of the phenotype under selection. Here we show frequency-dependent selection in a well-known natural genetic polymorphism affecting fruitfly foraging behaviour. When raised in low nutrient conditions, both of the naturally occurring alleles of the foraging gene (fors and forR) have their highest fitness when rare—the hallmark of negative frequency-dependent selection. This effect disappears at higher resources levels, demonstrating the role of larval competition. We are able to confirm the involvement of the foraging gene by showing that a sitter-like mutant allele on a rover background has similar frequency-dependent fitness as the natural sitter allele. Our study represents a clear demonstration of frequency-dependent selection, and we are able to attribute this effect to a single, naturally polymorphic gene known to affect behaviour.

Natural polymorphism affecting learning and memory in Drosophila

Knowing which genes contribute to natural variation in learning and memory would help us understand how differences in these cognitive traits evolve among populations and species. We show that a natural polymorphism at the foraging (for) locus, which encodes a cGMP-dependent protein kinase (PKG), affects associative olfactory learning in Drosophila melanogaster. In an assay that tests the ability to associate an odor with mechanical shock, flies homozygous for one natural allelic variant of this gene (forR) showed better short-term but poorer long-term memory than flies homozygous for another natural allele (fors). The fors allele is characterized by reduced PKG activity. We showed that forR-like levels of both short-term learning and long-term memory can be induced in fors flies by selectively increasing the level of PKG in the mushroom bodies, which are centers of olfactory learning in the fly brain. Thus, the natural polymorphism at for may mediate an evolutionary tradeoff between short- and long-term memory. The respective strengths of learning performance of the two genotypes seem coadapted with their effects on foraging behavior: forR flies move more between food patches and so could particularly benefit from fast learning, whereas fors flies are more sedentary, which should favor good long-term memory.

Epigenetic regulation of learning and memory by Drosophila EHMT/G9a.

Behavioral phenotyping and genome-wide profiling of the histone modifier EHMT in Drosophila reveals a mechanism through which an epigenetic writer may control cognition.

Natural variation in Drosophila melanogaster diapause due to the insulin-regulated PI3-kinase

This study links natural variation in a Drosophila melanogaster overwintering strategy, diapause, to the insulin-regulated phosphatidylinositol 3-kinase (PI3-kinase) gene, Dp110. Variation in diapause, a reproductive arrest, was associated with Dp110 by using Dp110 deletions and genomic rescue fragments in transgenic flies. Deletions of Dp110 increased the proportion of individuals in diapause, whereas expression of Dp110 in the nervous system, but not including the visual system, decreased it. The roles of phosphatidylinositol 3-kinase for both diapause in D. melanogaster and dauer formation in Caenorhabditis elegans suggest a conserved role for this kinase in both reproductive and developmental arrests in response to environmental stresses.

Social Interactions in “Simple” Model Systems

Deciphering the genetic and neurobiological underpinnings of social behavior is a difficult task. Simple model organisms such as C. elegans, Drosophila, and social insects display a wealth of social behaviors similar to those in more complex animals, including social dominance, group decision making, learning from experienced individuals, and foraging in groups. Although the study of social interactions is still in its infancy, the ability to assess the contributions of gene expression, neural circuitry, and the environment in response to social context in these simple model organisms is unsurpassed. Here, I take a comparative approach, discussing selected examples of social behavior across species and highlighting the common themes that emerge.

Heredity of rover/sitter: Alternative foraging strategies of Drosophila melanogaster larvae

The heredity of rover/sitter, a naturally occurring polymorphism in the locomotory component of Drosophila melanogaster third instar larval foraging behaviour was analysed by comparing 16 reciprocal crosses made using isogenic rover and sitter parental strains. Results from both male and female data sets indicated that rover/sitter differences have an autosomal basis, with rover showing complete dominance over sitter. The Y-chromosome, permanent cytoplasmic factors, transient maternal factors and interactions between them made no significant contributions to rover/sitter inheritance. A minor X-chromosome effect was observed in the female data. Rover/sitter ratios in both males and females of the 16 reciprocal crosses were not significantly different from those expected assuming a one gene, complete dominance model of autosomal inheritance.

Natural variation in food acquisition mediated via a Drosophila cGMP-dependent protein kinase

SUMMARY In natural environments where food abundance and quality can change drastically over time, animals must continuously alter their food acquisition strategies. Although genetic variation contributes to this plasticity, the specific genes involved and their interactions with the environment are poorly understood. Here we report that natural variation in the Drosophila gene, foraging (for), which encodes a cGMP-dependent protein kinase (PKG), affects larval food acquisition in an environmentally dependent fashion. When food is plentiful, the wild-type rover (forR) allele confers lower food intake and higher glucose absorption than both the wild-type sitter (fors) allele and the mutant fors2 allele. When food is scarce, forR, fors and fors2 larvae increase food intake to a common maximal level, but forR larvae retain their increased absorption efficiency. Changes in for expression can induce corrective behavioral modifications in response to food deprivation. When reared in environments with low food levels, forR larvae have higher survivorship and faster development than fors and fors2 larvae. Together, these results show that natural variation in for has far reaching implications affecting a suite of phenotypes involved in the regulation of food acquisition.