Michael R. Rose

Pathological gambling is linked to reduced activation of the mesolimbic reward system

By analogy to drug dependence, it has been speculated that the underlying pathology in pathological gambling is a reduction in the sensitivity of the reward system. Studying pathological gamblers and controls during a guessing game using functional magnetic resonance imaging, we observed a reduction of ventral striatal and ventromedial prefrontal activation in the pathological gamblers that was negatively correlated with gambling severity, linking hypoactivation of these areas to disease severity.

119th ENMC international workshop: Trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003, Naarden, The Netherlands

Department of Neurology, University Medical Center, Heidelberg laan 100, Utrecht, CX 3584, The Netherlands Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA The Walton Centre for Neurology and Neurosurgery, Liverpool, UK Department of Rheumatology, King’s College Hospital, London, UK Rheumatology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden King’s Neurosciences Centre, King’s College Hospital, London, UK Institute of Rheumatology, Prague, Czech Republic Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands Department of Clinical Neurosciences, Guy’s, King’s and Thomas’ School of Medicine, London, UK

Phenotypic plasticity and selection in Drosophila life-history evolution. I. Nutrition and the cost of reproduction

While it is commonplace for biologists to use the response to environmental manipulation as a guide to evolutionary responses to selection, the relationship between phenotypic plasticity and genetic change is not generally well‐established. The life‐histories of laboratory Drosophila populations are among the few experimental systems which simultaneously afford information on phenotypic plasticity and evolutionary trajectories. We employed a combination of two replicated selectively differentiated stocks (postponed aging stocks and their controls; 10 populations in total) and two different environmental manipulations (nutrition and mating) to explore the empirical relationship between phenotypic plasticity and evolutionary trajectories. While there are a number of parallels between the results obtained using these two approaches, there are important differences. In particular, as the detail of the biological characterization of either type of response increases, so their disparities multiply. Nonetheless, the combination of environmental manipulation with evolutionary divergence provides valuable information about the biological connections between life‐history, caloric reserves, and reproductive physiology in Drososphila.

GENETIC COVARIATION AMONG LIFE-HISTORY COMPONENTS: THE EFFECT OF NOVEL ENVIRONMENTS

gaster as estimated using compound-autosome strains. Evolution 33:359-370. MITCHELL, J. A., AND M. J. SIMMONS. 1977. Fitness effects of EMS induced mutations on the X chromosome of Drosophila melanogaster. II. Hemizygous fitnesseffects. Genetics 87:775-783. MUKAI, T., S. CHIGUSA, AND I. YOSHIKAWA. 1965. The genetic structure of natural populations of Drosophila melanogaster. III. Dominance effect of spontaneous mutant polygenescontrolling viability in heterozygous genetic background. Genetics 52:493-501.

Antagonistic pleiotropy, dominance and genetic variation

SummaryAlthough the importance of antagonistic pleiotropy of genes affecting components of fitness has long been argued, explicit population genetic models involving pleiotropy have only recently been developed. Simple, deterministic models of this kind are given, and then analyzed for conditions sufficient for protected polymorphism. It is found that dominance in gene action plays a key role in fostering the establishment of polymorphism in these models. However, the genetic variance for individual fitness components generally remains predominantly additive in spite of this. Though these models are not very robust, they do illustrate in principle one means of explaining recent experimental findings concerning the quantitative genetics of components of fitness in populations free of inbreeding.

Hormones and the Physiological Architecture of Life History Evolution

Hormones play key roles in the regulation of animal and plant life histories, particularly in the timing of transitions between prematurational stages and in the scheduling of reproduction. Furthermore, hormonal mechanisms are subject to information about the external and internal environment of the individual. Within an evolutionary radiation, the same hormone subsets often regulate the schedules of development as well as adult reproduction and related activities and, moreover, are involved in mechanisms of senescence. We propose that the pleiotropic and epistatic effects from hormonal and neural mechanisms are an important substratum for life history evolution. This analysis of hormonal mechanisms in senescence implicates a role for antagonistic pleiotropy in selection for particular subsets of hormonal mechanisms that can be traced throughout prematurational and postmaturational stages. In the example of the vertebrate MHC (major histocompatibility complex), polymorphic loci have been assembled with pleiotropic actions on several regulatory axes affecting reproduction and other fitness components. We argue that the MHC and other complex loci may be considered as life history gene complexes, with pleiotropic influences throughout the lifespan. While analyses of this kind might suggest that life histories could be evolutionarily rigid, in our interpretation the population genetics that is involved provides a theoretical basis for great flexibility in hormonal regulation during life history evolution. It is possible that life history evolution among taxonomic groups may sometimes be chaotic, which would frustrate strong inferences by the comparative method in the study of life histories between taxonomic groups.

Genome-wide analysis of a long-term evolution experiment with Drosophila

Experimental evolution systems allow the genomic study of adaptation, and so far this has been done primarily in asexual systems with small genomes, such as bacteria and yeast. Here we present whole-genome resequencing data from Drosophila melanogaster populations that have experienced over 600 generations of laboratory selection for accelerated development. Flies in these selected populations develop from egg to adult ∼20% faster than flies of ancestral control populations, and have evolved a number of other correlated phenotypes. On the basis of 688,520 intermediate-frequency, high-quality single nucleotide polymorphisms, we identify several dozen genomic regions that show strong allele frequency differentiation between a pooled sample of five replicate populations selected for accelerated development and pooled controls. On the basis of resequencing data from a single replicate population with accelerated development, as well as single nucleotide polymorphism data from individual flies from each replicate population, we infer little allele frequency differentiation between replicate populations within a selection treatment. Signatures of selection are qualitatively different than what has been observed in asexual species; in our sexual populations, adaptation is not associated with ‘classic’ sweeps whereby newly arising, unconditionally advantageous mutations become fixed. More parsimonious explanations include ‘incomplete’ sweep models, in which mutations have not had enough time to fix, and ‘soft’ sweep models, in which selection acts on pre-existing, common genetic variants. We conclude that, at least for life history characters such as development time, unconditionally advantageous alleles rarely arise, are associated with small net fitness gains or cannot fix because selection coefficients change over time.

Resistance to Environmental Stress in Drosophila melanogaster Selected for Postponed Senescence

Adult Drosophila melanogaster from populations that exhibit postponed senescence were compared to flies from control populations. Male and female flies from populations displaying postponed senescence were significantly more resistant than control flies to desiccation, starvation, and the vapor of a 15% ethanol solution. In the presence of desiccant or when humidity was not controlled, flies from postponed-senescence populations were more resistant than controls to heat stress in the range 37-39 C. Differences in heat tolerance disappeared when experiments were conducted at high humidity. Tolerance to starvation increased with age for females but remained approximately constant for males. Tolerance to desiccation decreased with age for both sexes. Differences between control and postponed-senescence populations with respect to starvation resistance and desiccation resistance were obtained at all ages examined. Females from postponed-senescence populations had lower proportional water content than did females from control populations. Differences in water content cannot explain the greater desiccation resistance of flies from postponed-senescence populations. Genetically increased life span in these D. melanogaster populations appears to result proximally from greater resistance to mortality arising from environmental stress.

Selection on stress resistance increases longevity in Drosophila melanogaster

Tests for the causal involvement of specific physiological mechanisms in the control of aging require evidence that these mechanisms can be used to increase longevity or reproductive lifespan. Selection for later reproduction in Drosophila has been shown to lead to increased longevity, as well as increased resistance to starvation and desiccation stresses. Selection for increased resistance to starvation and desiccation in Drosophila melanogaster is here shown to lead to increased longevity, indicating that alleles that increase stress resistance also may increase longevity. The responses of desiccation and starvation resistance to selection are partly independent of each other, indicating a multiplicity of physiological mechanisms involved in selectively postponed aging, and thus aging in general.

COMPLEX TRADE-OFFS AND THE EVOLUTION OF STARVATION RESISTANCE IN DROSOPHILA MELANOGASTER

The measurement of trade‐offs may be complicated when selection exploits multiple avenues of adaptation or multiple life‐cycle stages. We surveyed 10 populations of Drosophila melanogaster selected for increased resistance to starvation for 60 generations, their paired controls, and their mutual ancestors (a total of 30 outbred populations) for evidence of physiological and life‐history trade‐offs that span life‐cycle stages. The directly selected lines showed an impressive response to starvation selection, with mature adult females resisting starvation death 4–6 times longer than unselected controls or ancestors—up to a maximum of almost 20 days. Starvation‐selected flies are already 80% more resistant to starvation death than their controls immediately upon eclosion, suggesting that a significant portion of their selection response was owing to preadult growth and acquisition of metabolites relevant to the stress. These same lines exhibited significantly longer development and lower viability in the larval and pupal stages. Weight and lipid measurements on one of the starvation‐selected treatments (SB1–5), its control populations (CB1–5), and their ancestor populations (B1–5) revealed three important findings. First, starvation resistance and lipid content were linearly correlated; second, larval lipid acquisition played a major role in the evolution of adult starvation resistance; finally, increased larval growth rate and lipid acquisition had a fitness cost exacted in reduced viability and slower development. This study implicates multiple life‐cycle stages in the response to selection for the stress resistance of only one stage. Our starvation‐selected populations illustrate a case that may be common in nature. Patterns of genetic correlation may prove misleading unless multiple pleiotropic interconnections are resolved.