A test of quantitative genetic theory using Drosophila- effects of inbreeding and rate of inbreeding on heritabilities and variance components

Inbreeding is expected to decrease the heritability within populations. However, results from empirical studies are inconclusive. In this study, we investigated the effects of three breeding treatments (fast and slow rate of inbreeding - inbred to the same absolute level - and a control) on heritability, phenotypic, genetic and environmental variances of sternopleural bristle number in Drosophila melanogaster. Heritability, and phenotypic, genetic and environmental variances were estimated in 10 replicate lines within each of the three treatments. Standard least squares regression models and Bayesian methods were used to analyse the data. Heritability and additive genetic variance within lines were higher in the control compared with both inbreeding treatments. Heritabilities and additive genetic variances within lines were higher in slow compared with fast inbred lines, indicating that slow inbred lines retain more evolutionary potential despite the same expected absolute level of inbreeding. The between line variance was larger with inbreeding and more than twice as large in the fast than in the slow inbred lines. The different pattern of redistribution of genetic variance within and between lines in the two inbred treatments cannot be explained invoking the standard model based on selective neutrality and additive gene action. Environmental variances were higher with inbreeding, and more so with fast inbreeding, indicating that inbreeding and the rate of inbreeding affect environmental sensitivity. The phenotypic variance decreased with inbreeding, but was not affected by the rate of inbreeding. No inbreeding depression for mean sternopleural bristle number was observed in this study. Considerable variance between lines in additive genetic variance within lines was observed, illustrating between line variation in evolutionary potential.     

A TEST AND REVIEW OF THE ROLE OF EFFECTIVE POPULATION SIZE ON EXPERIMENTAL SEXUAL SELECTION PATTERNS

Experimental evolution, particularly experimental sexual selection in which sexual selection strength is manipulated by altering the mating system, is an increasingly popular method for testing evolutionary theory. Concerns have arisen regarding genetic diversity variation across experimental treatments: differences in the number and sex ratio of breeders (effective population size; N_e ) and the potential for genetic hitchhiking, both of which may cause different levels of genetic variation between treatments. Such differences may affect the selection response and confound interpretation of results. Here we use both census-based estimators and molecular marker-based estimates to empirically test how experimental evolution of sexual selection in Drosophila pseudoobscura impacts N_e and autosomal genetic diversity. We also consider effects of treatment on X-linked N_e s, which have previously been ignored. Molecular autosomal marker-based estimators indicate that neither N_e nor genetic diversity differs between treatments experiencing different sexual selection intensities; thus observed evolutionary responses reflect selection rather than any confounding effects of experimental design. Given the increasing number of studies on experimental sexual selection, we also review the census N_e s of other experimental systems, calculate X-linked N_e , and compare how different studies have dealt with the issues of inbreeding, genetic drift, and genetic hitchhiking to help inform future designs.     

Rapid genetic divergence in response to 15 years of simulated climate change

Genetic diversity may play an important role in allowing individual species to resist climate change, by permitting evolutionary responses. Our understanding of the potential for such responses to climate change remains limited, and very few experimental tests have been carried out within intact ecosystems. Here, we use amplified fragment length polymorphism (AFLP) data to assess genetic divergence and test for signatures of evolutionary change driven by long‐term simulated climate change applied to natural grassland at Buxton Climate Change Impacts Laboratory (BCCIL). Experimental climate treatments were applied to grassland plots for 15 years using a replicated and spatially blocked design and included warming, drought and precipitation treatments. We detected significant genetic differentiation between climate change treatments and control plots in two coexisting perennial plant study species (Festuca ovina and Plantago lanceolata). Outlier analyses revealed a consistent signature of selection associated with experimental climate treatments at individual AFLP loci in P. lanceolata, but not in F. ovina. Average background differentiation at putatively neutral AFLP loci was close to zero, and genomewide genetic structure was associated neither with species abundance changes (demography) nor with plant community‐level responses to long‐term climate treatments. Our results demonstrate genetic divergence in response to a suite of climatic environments in reproductively mature populations of two perennial plant species and are consistent with an evolutionary response to climatic selection in P. lanceolata. These genetic changes have occurred in parallel with impacts on plant community structure and may have contributed to the persistence of individual species through 15 years of simulated climate change at BCCIL.     

Ethnic difference in osteoporosis-related phenotypes and its potential underlying genetic determination

Osteoporosis is a serious health problem in both Caucasians and Asians. Caucasians and Asians are two distinct major ethnic groups, which may have differential genetic determination underlying complex genetic diseases such as osteoporosis. However, to date, there has been no systematic review focusing on the aspect of ethnic difference in risk to osteoporosis and its potential underlying genetic determination between Asians and Caucasians. Here, we firstly review diverse aspects of osteoporosis-related differences, including the differences of epidemiology of osteoporotic fractures, peak bone mass, bone loss, bone area, bone geometry and drug treatment response between Asians and Caucasians. Then, we provide some potential genetic evidence on the different heritability and inheritance mode of bone phenotypes, the different osteoporosis candidate genes and the differential results in related molecular studies between them, to explain the above osteoporosis-related phenotypic differences. The results suggest that the osteoporosis-related phenotypic differences between Asians and Caucasians may be partially the result of the different ethnic genetic background. The present review may increase our understanding of potential different mechanisms related to ethnicity in pathogenesis of osteoporosis for effective and potentially customized treatments in different major ethnic groups.     

GENETIC VARIATION FOR PHENOTYPIC PLASTICITY IN THE LARVAL LIFE HISTORY OF SPADEFOOT TOADS (SCAPHIOPUS COUCHII)

Phenotypic plasticity in life-history traits is common. The relationship between phenotype and environment, or reaction norm, associated with life-history plasticity can evolve by natural selection if there is genetic variation within a population for the reaction norm and if the traits involved affect fitness. As with other traits, selection on plasticity in a particular trait or in response to a particular environmental factor may be constrained by trade-offs with other traits that affect fitness. In this paper, I experimentally evaluated broad-sense genetic variation in the reaction norms of age and size at metamorphosis in response to two environmental factors, food level and temperature. Differences among full-sib families in one or both traits were evident in all treatments. However, variation among families in their responses to each treatment (genotype-environment interaction) resulted in variation among treatments in estimated heritabilities and genetic correlations. Age at metamorphosis was equally sensitive to temperature in all families, but size at metamorphosis was more sensitive to temperature in some families than in others. Size at metamorphosis was equally sensitive to food level in all families, but age at metamorphosis was sensitive to food in some families but not in others. At high temperature or low food, the genetic correlation between age and size at metamorphosis was positive, generating a potential trade-off between metamorphosing early to attain higher larval survival and metamorphosing later to achieve larger size. This trade-off extends across treatments: families with the largest average size at metamorphosis achieved larger size with the longest average and greatest plasticity in age at metamorphosis. Other families achieved shorter average larval periods by exhibiting greater plasticity in size at metamorphosis but had the smallest average size at metamorphosis. This trade-off may reflect an underlying functional constraint on the ability to respond optimally to all environments, resulting in persistent genetic variation in reaction norms.     

Towards gene therapy for the central nervous system

Gene therapy has generated enormous scientific, medical and public interest over the last decade. Clinical trials involving approximately 2000 patients worldwide have targeted simple genetic diseases such as cystic fibrosis, muscular dystrophy, adenosine deaminase deficiency, Gaucher's disease and familial hypercholesterolemia, as well as complex acquired diseases such as cancer and AIDS. The central nervous system is a new and particularly exciting target for gene therapy because its unique properties prevent the successful treatment of many neurological disorders by conventional means. This review discusses the potential applications of in vivo gene therapy to neurological disorders that have the greatest potential for genetic treatments.     

Bioengineered microbes in disease therapy

Naturally occurring microorganisms have been used therapeutically for over a century, but the advent of modern techniques for genetic manipulation has created unprecedented opportunities to develop novel bioengineered microbes with high therapeutic efficacy. Engineered bacteria can be tailored to deliver drugs, therapeutic proteins, and gene therapy vectors with great efficiency, and with a higher degree of site-specificity than conventional administration regimes. Moreover, they provide new opportunities to interfere with critical steps in disease pathogenesis. In this review, we present a cross-section of recent work on the development of bacterial-mediated treatments for inflammatory disorders, infectious diseases, and cancer. These treatments have the potential to significantly impact global morbidity and mortality if successfully translated from the laboratory into the clinic.     

Genetic and environmental control of temporal and size-dependent sex allocation in a wind-pollinated plant

Sex allocation in hermaphrodites can be affected by spatial and temporal variation in resources, especially in plants where size-dependent gender modification is commonplace. The evolution of sex allocation will depend on the relative importance of genetic and environmental factors governing patterns of investment in female and male function. In wind-pollinated plants, theoretical models predict a positive relation between size and male investment because of the fitness advantages associated with more effective pollen dispersal. Theory also predicts that the timing and allocation to each sex function should depend on available resources. We grew maternal half-sibling families of annual, wind-pollinated, Ambrosia artemisiifolia in sun and shade treatments to investigate these predictions. There was significant genetic variation for female and male flower production in both sun and shade treatments. Size-dependent sex allocation occurred in the direction predicted by theory, with male flower production increasing more rapidly in larger plants. The timing of sex function also varied, with significant genetic variation for dichogamy within environments and plasticity of this trait between environments. Protandry was expressed more commonly in the sun and protogyny in the shade. The occurrence of dynamic sex allocation with changing size and experimental treatment indicates the potential for adaptive responses under different ecological conditions.     

Climate change shifts natural selection and the adaptive potential of the perennial forb Boechera stricta in the Rocky Mountains

Heritable genetic variation is necessary for populations to evolve in response to anthropogenic climate change. However, antagonistic genetic correlations among traits may constrain the rate of adaptation, even if substantial genetic variation exists. We examine potential genetic responses to selection by comparing multivariate genetic variance–covariances of traits and fitness (multivariate Robertson–Price identities) across different environments in a reciprocal transplant experiment of the forb Boechera stricta in the Rocky Mountains. By transplanting populations into four common gardens arrayed along an elevational gradient, and exposing populations to control and snow removal treatments, we simulated future and current climates and snowmelt regimes. Genetic variation in flowering and germination phenology declined in plants moved downslope to warmer, drier sites, suggesting that these traits may have a limited ability to evolve under future climates. Simulated climate change via snow removal altered the strength of selection on flowering traits, but we found little evidence that genetic correlations among traits are likely to affect the rate of adaptation to climate change. Overall, our results suggest that climate change may alter the evolutionary potential of B. stricta, but reduced expression of genetic variation may be a larger impediment to adaptation than constraints imposed by antagonistic genetic correlations.     

Individual organisms as units of analysis: Bayesian-clustering alternatives in population genetics

Population genetic analyses traditionally focus on the frequencies of alleles or genotypes in 'populations' that are delimited a priori. However, there are potential drawbacks of amalgamating genetic data into such composite attributes of assemblages of specimens: genetic information on individual specimens is lost or submerged as an inherent part of the analysis. A potential also exists for circular reasoning when a population's initial identification and subsequent genetic characterization are coupled. In principle, these problems are circumvented by some newer methods of population identification and individual assignment based on statistical clustering of specimen genotypes. Here we evaluate a recent method in this genre--Bayesian clustering--using four genotypic data sets involving different types of molecular markers in non-model organisms from nature. As expected, measures of population genetic structure (F(ST) and phiST) tended to be significantly greater in Bayesian a posteriori data treatments than in analyses where populations were delimited a priori. In the four biological contexts examined, which involved both geographic population structures and hybrid zones, Bayesian clustering was able to recover differentiated populations, and Bayesian assignments were able to identify likely population sources of specific individuals.     

Non‐consumptive effects of predation: does perceived risk strengthen the genetic integration of behaviour and morphology in stickleback?

Predators can shape genetic correlations in prey by altering prey perception of risk. We manipulated perceived risk to test whether such non‐consumptive effects tightened behavioural trait correlations in wild‐caught stickleback from high‐ compared to low‐risk environments due to genetic variation in plasticity. We expected tighter genetic correlations within perceived risk treatments than across them, and tighter genetic correlations in high‐risk than in low‐risk treatments. We identified genetic variation in plasticity, with genetic correlations between boldness, sociality, and antipredator morphology, as expected, being tighter within treatments than across them, for both of two populations. By contrast, genetic correlations did not tighten with exposure to risk. Tighter phenotypic correlations in wild stickleback may thus arise because predators induce correlational selection on environmental components of these traits, or because predators tighten residual correlations by causing environmental heterogeneity that is controlled in the laboratory. Our study places phenotypic integration firmly into an ecological context.     

Intraspecific litter diversity and nitrogen deposition affect nutrient dynamics and soil respiration

Anthropogenic forces are concurrently reducing biodiversity and altering terrestrial nutrient cycles. As natural populations decline, genetic diversity within single species also declines. The consequences of intraspecific genetic loss for ecosystem functions are poorly understood, and interactions among intraspecific diversity, nitrogen deposition, and nutrient cycling are unknown. We present results from an experiment that simulated both a decline in biodiversity and an increase in nitrogen deposition. In soil microcosms, we tested effects of variation in intraspecific litter diversity and nitrogen deposition on soil respiration and nitrogen leaching. Increases in intraspecific litter diversity increased soil respiration overall, with the greatest increases in respiration occurring under high nitrogen deposition. Nitrogen deposition increased the amount of inorganic nitrogen leached, while the amount of dissolved organic nitrogen leached was correlated with initial litter chemistry (lignin concentration) and remained independent of litter diversity and nitrogen deposition treatments. Our results demonstrate the potential for losses in genetic diversity to interact with other global environmental changes to influence terrestrial nutrient cycles.     

Cytokine pharmacogenetics

Genetic variation plays a significant role in the normal functioning of the immune system, and also in the interaction between many common drugs and cellular pathways. With a growing number of cytokine-based therapies now in mainstream clinical use, the prospect of targeting these agents to the individuals likely to benefit from them most is an appealing one. This review outlines the potential clinical impact of cytokine pharmacogenetics in targeting these therapies to individuals with favourable genetic profiles. The use of such approaches may have important pharmacoeconomic benefits and lead to improved therapeutic profiles for these treatments.     

In vitro gametogenesis from embryonic stem cells

Many insights into mammalian germ cell development have been gained through genetic engineering and in vivo studies, but the lack of an in vitro system for deriving germ cells has hindered potential advances in germ cell biology. Recent studies have demonstrated embryonic stem cell differentiation into germ cells and more mature gametes, although significant unanswered questions remain about the functionality of these cells. The derivation of germ cells from embryonic stem cells in vitro provides an invaluable assay both for the genetic dissection of germ cell development and for epigenetic reprogramming, and may one day facilitate nuclear transfer technology and infertility treatments.     

Response of a diuron-degrading community to diuron exposure assessed by real-time quantitative PCR monitoring of phenylurea hydrolase A and B encoding genes

A real-time quantitative PCR method was developed to detect and quantify phenlylurea hydrolase genes’ (puhA and puhB) sequences from environmental DNA samples to assess diuron-degrading genetic potential in some soil and sediment microbial communities. In the soil communities, mineralization rates (determined with [ring-¹⁴C]-labeled diuron) were linked to diuron-degrading genetic potentials estimated from puhB number copies, which increased following repeated diuron treatments. In the sediment communities, mineralization potential did not depend solely on the quantity of puhB copies, underlining the need to assess gene expression. In the sediment samples, both puhB copy numbers and mineralization capacities were highly conditioned by whether or not diuron-treated soil was added. This points to transfers of degradative potential from soils to sediments. No puhA gene was detected in soil and sediment DNA extracts. Moreover, some sediments exhibited high diuron mineralization potential even though puhB genes were not detected, suggesting the existence of alternative diuron degradation pathways.     

Genetic diversity and invasibility: a test using a model system with a novel experimental design

Biological invasion is one aspect of ecosystem function that may be controlled by the biological diversity of the invaded community, and there have been a number of recent studies that investigated relationships between diversity and invasibility. Most experimental studies report that higher species or functional group diversity increases resistance to invasion, but the role of genetic diversity is unknown. We used a model organism, Arabidopsis thaliana (Brassicaceae), to investigate relationships between genotypic richness and community invasibility by creating communities with 1, 2, 4, and 8 genotypes of A. thaliana at constant low (417 plants m⁻²) and high (834 plants m⁻²) densities, that once established, were invaded with a congener, Arabidopsis suecica. To reduce the potential effects of methodological confounding related to “sampling effects,”“variance reduction effects,” or confounding of abundance with diversity, we (1) created random communities from a relatively large pool of functionally and phenotypically similar genotypes, (2) evaluated individual and community traits across richness treatments, and (3) analyzed similarity of communities within treatments (for “quasi- replication”) and between adjacent treatments (for “nestedness”). Genotypic richness had no effect on A. suecica demography (emergence, survivorship), size (biomass, rosette area), or reproductive potential (rates of bolting and fruiting or number and size of bolts). In contrast, the density of A. thaliana genotypes had strong effects on the size and reproductive potential of A. suecica, which suggests that characteristics of the recipient community other than genotypic richness (e.g. light) form the most important determinant of community invasibility. Individual- and community-level traits of community members (cover, biomass, survivorship) did not differ among richness treatments, and within- and between-treatment similarity was reduced (relative to other recent experiments) but not eliminated. We evaluate our results vis-a-vis recent analyses of diversity-invasibility experiments, and provide directions for future investigations of genetic diversity.     

Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages

Emil Kraepelin would clearly recognize his 19th century dichotomy within current operational classifications of psychosis. However, he might be surprised at its survival, given the extent to which it has been undermined by the weight of currently available empirical evidence. The failure of this evidence to influence diagnostic practice reflects not only the comfortable simplicity of the dichotomous approach, but also the fact that this approach has for many years continued to receive support from some areas of research, particularly genetic epidemiology. This, however, is changing and findings from genetic epidemiology are being reappraised. More importantly, the potential of molecular genetics to indicate biological systems involved in psychopathology has been recognized, and with it the potential to develop diagnostic classifications that have greater biological validity. Crucially, this will facilitate diagnostic schemes with much greater clinical utility, allowing clinicians to select treatments based on underlying pathogenesis. Recent molecular genetic findings have demonstrated very clearly the inadequacies of the dichotomous view, and highlighted the importance of better classifying cases with both psychotic and affective symptoms. In this article we discuss these issues and suggest ways forward, both immediately and for DSM-V and ICD-11. If psychiatry is to translate the opportunities offered by new research methodologies, we must move to a classificatory approach that is worthy of the 21st century.     

The effects of genotype, age, and social environment on male ornamentation, mating behavior, and attractiveness

The traits thought to advertise genetic quality are often highly susceptible to environmental variation and prone to change with age. These factors may either undermine or reinforce the potential for advertisement traits to signal quality depending on the magnitude of age-dependent expression, environmental variation, and genotype-age and genotype-environment interaction. Measurements of the magnitude of these effects are thus a necessary step toward assessing the implications of age dependence and environmental variability for the evolution of signals of quality. We conducted a longitudinal study of male guppies (Poecilia reticulata) from 22 full-sibling families. Each fish was assigned at maturity to one of three treatments in order to manipulate his allocation of resources to reproduction: a control in which the male was kept alone, a courtship-only treatment in which he could see and court a female across a clear partition, and a mating treatment in which he interacted freely with a female. We measured each male's size, ornamental color patterns, courtship, attractiveness to females, and mating success at three ages. Size was influenced by treatment and age-treatment interactions, indicating that courtship and mating may impose costs on growth. Tail size and color patterns were influenced by age but not by treatment, suggesting fixed age-dependent trajectories in these advertisement traits. By contrast, display rate and attempted sneak copulation rate differed among treatments but not among ages, suggesting greater plasticity of these behavioral traits. As a result of the different patterns of variation in ornamentation and behavior, male attractiveness and mating success responded to male age, treatment, and the interaction between age and treatment. Neither age nor treatment obscured the presence of genetic variation, and the genetic relationship between male ornamentation and attractiveness remained the same among treatments. Our findings suggest that neither age-dependent variation nor environmentally induced variation in reproductive effort is likely to undermine the reliability of male signaling.     

Genetic characterization of heather (Calluna vulgaris (L.) hull) subject to different management regimes across great britain

Heather plants were collected from 34 populations in Great Britain, which differed according to their geographical location and associated management histories. Comparisons of differential grazing regimes were made across 10 sites in the first year of study, whereas the influence of differential burning regimes was considered at four sites during the second year. The extent of genetic variation, both within and between the selected heather populations, was examined using polymerase chain reaction (PCR)-based DNA fingerprinting methodologies. Initially, high genetic variation within populations obscured differences between populations. Heather stands that were geographically close proved to be genetically similar. Site latitude and longitude were strongly associated with genetic differences between heather populations; however, a range of grazing and burning management treatments had no consistent effect upon genetic diversity. The results represent the first national survey of genetic variation at the DNA level within UK populations of this important heathland species. They provided insights into the genetic structure of heather-dominated heathlands, revealing a lack of clonal dominance within populations, but rather a much more varied genetic makeup than might have been expected given the species' ability to propagate vegetatively. The processes that influence genetic diversity in heather populations are discussed, and the potential role of molecular techniques in heathland conservation is considered.