Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

A combination of l-arabinose and chromium lowers circulating glucose and insulin levels after an acute oral sucrose challenge

<p>Abstract</p> <p>Background</p> <p>A growing body of research suggests that elevated circulating levels of glucose and insulin accelerate risk factors for a wide range of disorders. Low-risk interventions that could suppress glucose without raising insulin levels could offer significant long-term health benefits.</p> <p>Methods</p> <p>To address this issue, we conducted two sequential studies, the first with two phases. In the first phase of Study 1, baseline fasting blood glucose was measured in 20 subjects who consumed 70 grams of sucrose in water and subsequently completed capillary glucose measurements at 30, 45, 60 and 90 minutes (Control). On day-2 the same procedure was followed, but with subjects simultaneously consuming a novel formula containing l-arabinose and a trivalent patented food source of chromium (LA-Cr) (Treatment). The presence or absence of the LA-Cr was blinded to the subjects and testing technician. Comparisons of changes from baseline were made between Control and Treatment periods. In the second phase of Study 1, 10 subjects selected from the original 20 competed baseline measures of body composition (DXA), a 43-blood chemistry panel and a Quality of Life Inventory. These subjects subsequently took LA-Cr daily for 4 weeks completing daily tracking forms and repeating the baseline capillary tests at the end of each of the four weeks. In Study 2, the same procedures used in the first phase were repeated for 50 subjects, but with added circulating insulin measurements at 30 and 60 minutes from baseline.</p> <p>Results</p> <p>In both studies, as compared to Control, the Treatment group had significantly lower glucose responses for all four testing times (AUC = <it>P </it>< 0.0001). Additionally, the Treatment was significantly more effective in lowering circulating insulin after 60 minutes from baseline (AUC = <it>P </it>= < 0.01). No adverse effects were found after acute sucrose challenge or in those who consumed LA-Cr daily for four weeks.</p> <p>Conclusions</p> <p>As compared to a placebo control, consumption of a LA-Cr formula after a 70-gram sucrose challenge was effective in safely lowering both circulating glucose and insulin levels.</p> <p>Trial Registration</p> <p>Clinical Trials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT0110743">NCT0110743</a></p

Is Aquatic Life Correlated with an Increased Hematocrit in Snakes?

Background: Physiological adaptations that allow air-breathing vertebrates to remain underwater for long periods mainly involve modifications of the respiratory system, essentially through increased oxygen reserves. Physiological constraints on dive duration tend to be less critical for ectotherms than for endotherms because the former have lower mass-specific metabolic rates. Moreover, comparative studies between marine and terrestrial ectotherms have yet to show overall distinct physiological differences specifically associated with oxygen reserves. Methodology/Principal Findings: We used phylogenetically informed statistical models to test if habitat affects hematocrit (an indicator of blood oxygen stores) in snakes, a lineage that varies widely in habitat use. Our results indicate that both phylogenetic position (clade) and especially habitat are significant predictors of hematocrit. Our analysis also confirms the peculiar respiratory physiology of the marine Acrochordus granulatus. Conclusion/Significance: Contrary to previous findings, marine snakes have significantly–albeit slightly–elevated hematocrit, which should facilitate increased aerobic dive times. Longer dives could have consequences for foraging, mate searching, and predation risks. Alternatively, but not exclusively, increased Hct in marine species might also help t

An integrated workflow for robust alignment and simplified quantitative analysis of NMR spectrometry data

<p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique to reveal and compare quantitative metabolic profiles of biological tissues. However, chemical and physical sample variations make the analysis of the data challenging, and typically require the application of a number of preprocessing steps prior to data interpretation. For example, noise reduction, normalization, baseline correction, peak picking, spectrum alignment and statistical analysis are indispensable components in any NMR analysis pipeline.</p> <p>Results</p> <p>We introduce a novel suite of informatics tools for the quantitative analysis of NMR metabolomic profile data. The core of the processing cascade is a novel peak alignment algorithm, called hierarchical Cluster-based Peak Alignment (CluPA). The algorithm aligns a target spectrum to the reference spectrum in a top-down fashion by building a hierarchical cluster tree from peak lists of reference and target spectra and then dividing the spectra into smaller segments based on the most distant clusters of the tree. To reduce the computational time to estimate the spectral misalignment, the method makes use of Fast Fourier Transformation (FFT) cross-correlation. Since the method returns a high-quality alignment, we can propose a simple methodology to study the variability of the NMR spectra. For each aligned NMR data point the ratio of the between-group and within-group sum of squares (BW-ratio) is calculated to quantify the difference in variability between and within predefined groups of NMR spectra. This differential analysis is related to the calculation of the F-statistic or a one-way ANOVA, but without distributional assumptions. Statistical inference based on the BW-ratio is achieved by bootstrapping the null distribution from the experimental data.</p> <p>Conclusions</p> <p>The workflow performance was evaluated using a previously published dataset. Correlation maps, spectral and grey scale plots show clear improvements in comparison to other methods, and the down-to-earth quantitative analysis works well for the CluPA-aligned spectra. The whole workflow is embedded into a modular and statistically sound framework that is implemented as an R package called "speaq" ("spectrum alignment and quantitation"), which is freely available from <url>http://code.google.com/p/speaq/</url>.</p