Navigating the unknown: model selection in phylogeography. Models of population structure: tools for thinkers

Despite the widespread use and obvious strengths of model-based methods for phylogeographic study, a persistent concern for such analyses is related to the definition of the model itself. The study by Peter et al. (2010) in this issue of Molecular Ecology demonstrates an approach for overcoming such hurdles. The authors were motivated by a deceptively simple goal; they sought to infer whether a population has remained at a low and stable size or has undergone a decline, and certainly there is no shortage of software packages for such a task (e.g., see list of programs in Excoffier & Heckel 2006). However, each of these software packages makes basic assumptions about the underling population (e.g., is the population subdivided or panmictic); these assumptions are explicit to any model-based approach but can bias parameter estimates and produce misleading inferences if the model does not approximate the actual demographic history in a reasonable manner. Rather than guessing which model might be best for analyzing the data (microsatellite data from samples of chimpanzees), Peter et al. (2010) quantify the relative fit of competing models for estimating the population genetic parameters of interest. Complemented by a revealing simulation study, the authors highlight the peril inherent to model-based inferences that lack a statistical evaluation of the fit of a model to the data, while also demonstrating an approach for model selection with broad applicability to phylogeographic analysis.     

Direct exchange of vitamin B12 is demonstrated by modelling the growth dynamics of algal–bacterial cocultures

The growth dynamics of populations of interacting species in the aquatic environment is of great importance, both for understanding natural ecosystems and in efforts to cultivate these organisms for industrial purposes. Here we consider a simple two-species system wherein the bacterium Mesorhizobium loti supplies vitamin B₁₂ (cobalamin) to the freshwater green alga Lobomonas rostrata, which requires this organic micronutrient for growth. In return, the bacterium receives photosynthate from the alga. Mathematical models are developed that describe minimally the interdependence between the two organisms, and that fit the experimental observations of the consortium. These models enable us to distinguish between different mechanisms of nutrient exchange between the organisms, and provide strong evidence that, rather than undergoing simple lysis and release of nutrients into the medium, M. loti regulates the levels of cobalamin it produces, resulting in a true mutualism with L. rostrata. Over half of all microalgae are dependent on an exogenous source of cobalamin for growth, and this vitamin is synthesised only by bacteria; it is very likely that similar symbiotic interactions underpin algal productivity more generally.     

Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study

Background

Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV₁-decline in male heavy smokers.

Methods

3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV₁-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference.

Results

Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 – 14.1) and mean (SD) FEV₁ was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted ‘>5 years’ showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV₁-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001).

Conclusion

Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline.

Trial registration

Registered at http://www.trialregister.nl with trial number ISRCTN63545820.     

Conservation genetic inferences in the carnivorous pitcher plant <Emphasis Type=Italic>Sarracenia alata</Emphasis> (Sarraceniaceae)

Conservation geneticists make inferences about their focal species from genetic data, and then use these inferences to inform conservation decisions. Since different biological processes can produce similar patterns of genetic diversity, we advocate an approach to data analysis that considers the full range of evolutionary forces and attempts to evaluate their relative contributions in an objective manner. Here we collect data from microsatellites and chloroplast loci and use these data to explore models of historical demography in the carnivorous Pitcher Plant, Sarracenia alata. Findings indicate that populations of S. alata exhibit high degrees of population genetic structure, likely caused by dispersal limitation, and that population sizes have decreased in western populations and increased in eastern populations. These results provide new insight to the management and conservation of plants restricted to small, declining populations isolated in increasingly scarce and highly threatened habitat, including other rare and endangered species of Sarracenia.     

The Saccharomyces cerevisiae chitinase,encoded by the CTS1-2 gene,confers antifungal activity against Botrytis cinerea to Transgenic tobacco

The Saccharomyces cerevisiae chitinase, encoded by the CTS1-2 gene has recently been confirmed by in vitro tests to possess antifungal abilities. In this study, the CTS1-2 gene has been evaluated for its in planta antifungal activity by constitutive overexpression in tobacco plants to assess its potential to increase the plant's defence against fungal pathogens. Transgenic tobacco plants, generated by Agrobacterium-mediated transformation, showed stable integration and inheritance of the transgene. Northern blot analyses conducted on the transgenic tobacco plants confirmed transgene expression. Leaf extracts from the transgenic lines inhibited Botrytis cinerea spore germination and hyphal growth by up to 70% in a quantitative in vitro assay, leading to severe physical damage on the hyphae. Several of the F₁ progeny lines were challenged with the fungal pathogen, B. cinerea, in a detached leaf infection assay, showing a decrease in susceptibility ranging from 50 to 70%. The plant lines that showed increased disease tolerance were also shown to have higher chitinase activities.     

Applications of next-generation sequencing to phylogeography and phylogenetics

This is a time of unprecedented transition in DNA sequencing technologies. Next-generation sequencing (NGS) clearly holds promise for fast and cost-effective generation of multilocus sequence data for phylogeography and phylogenetics. However, the focus on non-model organisms, in addition to uncertainty about which sample preparation methods and analyses are appropriate for different research questions and evolutionary timescales, have contributed to a lag in the application of NGS to these fields. Here, we outline some of the major obstacles specific to the application of NGS to phylogeography and phylogenetics, including the focus on non-model organisms, the necessity of obtaining orthologous loci in a cost-effective manner, and the predominate use of gene trees in these fields. We describe the most promising methods of sample preparation that address these challenges. Methods that reduce the genome by restriction digest and manual size selection are most appropriate for studies at the intraspecific level, whereas methods that target specific genomic regions (i.e., target enrichment or sequence capture) have wider applicability from the population level to deep-level phylogenomics. Additionally, we give an overview of how to analyze NGS data to arrive at data sets applicable to the standard toolkit of phylogeography and phylogenetics, including initial data processing to alignment and genotype calling (both SNPs and loci involving many SNPs). Even though whole-genome sequencing is likely to become affordable rather soon, because phylogeography and phylogenetics rely on analysis of hundreds of individuals in many cases, methods that reduce the genome to a subset of loci should remain more cost-effective for some time to come.     

Distribution modelling and statistical phylogeography: an integrative framework for generating and testing alternative biogeographical hypotheses

Statistical phylogeographic studies contribute to our understanding of the factors that influence population divergence and speciation, and that ultimately generate biogeographical patterns. The use of coalescent modelling for analyses of genetic data provides a framework for statistically testing alternative hypotheses about the timing and pattern of divergence. However, the extent to which such approaches contribute to our understanding of biogeography depends on how well the alternative hypotheses chosen capture relevant aspects of species histories. New modelling techniques, which explicitly incorporate spatio-geographic data external to the gene trees themselves, provide a means for generating realistic phylogeographic hypotheses, even for taxa without a detailed fossil record. Here we illustrate how two such techniques – species distribution modelling and its historical extension, palaeodistribution modelling – in conjunction with coalescent simulations can be used to generate and test alternative hypotheses. In doing so, we highlight a few key studies that have creatively integrated both historical geographic and genetic data and argue for the wider incorporation of such explicit integrations in biogeographical studies.     

Identifying the neural circuitry of alcohol craving and relapse vulnerability

With no further intervention, relapse rates in detoxified alcoholics are high and usually exceed 80% of all detoxified patients. It has been suggested that stress and exposure to priming doses of alcohol and to alcohol-associated stimuli (cues) contribute to the relapse risk after detoxification. This article focuses on neuronal correlates of cue responses in detoxified alcoholics. Current brain imaging studies indicate that dysfunction of dopaminergic, glutamatergic and opioidergic neurotransmission in the brain reward system (ventral striatum including the nucleus accumbens) can be associated with alcohol craving and functional brain activation in neuronal systems that process attentional relevant stimuli, reward expectancy and experience. Increased functional brain activation elicited by such alcohol-associated cues predicted an increased relapse risk, whereas high brain activity elicited by affectively positive stimuli may represent a protective factor and was correlated with a decreased prospective relapse risk. These findings are discussed with respect to psychotherapeutic and pharmacological treatment options.     

Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.