Using Avida to test the effects of natural selection on phylogenetic reconstruction methods

Phylogenetic trees group organisms by their ancestral relationships. There are a number of distinct algorithms used to reconstruct these trees from molecular sequence data, but different methods sometimes give conflicting results. Since there are few precisely known phylogenies, simulations are typically used to test the quality of reconstruction algorithms. These simulations randomly evolve strings of symbols to produce a tree, and then the algorithms are run with the tree leaves as inputs. Here we use Avida to test two widely used reconstruction methods, which gives us the chance to observe the effect of natural selection on tree reconstruction. We find that if the organisms undergo natural selection between branch points, the methods will be successful even on very large time scales. However, these algorithms often falter when selection is absent

On Krein-like theorems for noncanonical Hamiltonian systems with continuous spectra: application to Vlasov-Poisson

The notions of spectral stability and the spectrum for the Vlasov-Poisson system linearized about homogeneous equilibria, f_0(v), are reviewed. Structural stability is reviewed and applied to perturbations of the linearized Vlasov operator through perturbations of f_0. We prove that for each f_0 there is an arbitrarily small delta f_0' in W^{1,1}(R) such that f_0+delta f_0$is unstable. When$f_0$ is perturbed by an area preserving rearrangement, f_0 will always be stable if the continuous spectrum is only of positive signature, where the signature of the continuous spectrum is defined as in previous work. If there is a signature change, then there is a rearrangement of f_0 that is unstable and arbitrarily close to f_0 with f_0' in W^{1,1}. This result is analogous to Krein's theorem for the continuous spectrum. We prove that if a discrete mode embedded in the continuous spectrum is surrounded by the opposite signature there is an infinitesimal perturbation in C^n norm that makes f_0 unstable. If f_0 is stable we prove that the signature of every discrete mode is the opposite of the continuum surrounding it.Comment: Submitted to the journal Transport Theory and Statistical Physics. 36 pages, 12 figure

Association between Acquired Uniparental Disomy and Homozygous Mutations and HER2/ER/PR Status in Breast Cancer

Background: Genetic alterations in cellular signaling networks are a hallmark of cancer, however, effective methods to discover them are lacking. A novel form of abnormality called acquired uniparental disomy (aUPD) was recently found to pinpoint the region of mutated genes in various cancers, thereby identifying the region for next-generation sequencing. Methods/Principal Findings: We retrieved large genomic data sets from the Gene Expression Omnibus database to perform genome-wide analysis of aUPD in breast tumor samples and cell lines using approaches that can reliably detect aUPD. Aupd was identified in 52.29% of the tumor samples. The most frequent aUPD regions were located at chromosomes 2q, 3p, 5q, 9p, 9q, 10q, 11q, 13q, 14q and 17q. We evaluated the data for any correlation between the most frequent aUPD regions and HER2/neu, ER, and PR status, and found a statistically significant correlation between the recurrent regions of aUPD and triple negative (TN) breast cancers. aUPD at chromosome 17q (VEZF1, WNT3), 3p (SUMF1, GRM7), 9p (MTAP, NFIB) and 11q (CASP1, CASP4, CASP5) are predictors for TN. The frequency of aUPD was found to be significantly higher in TN breast cancer cases compared to HER2/neu-positive and/or ER or PR-positive cases. Furthermore, using previously published mutation data, we found TP53 homozygously mutated in cell lines having aUPD in that locus. Conclusions/Significance: We conclude that aUPD is a common and non-random molecular feature of breast cancer that is most prominent in triple negative cases. As aUPD regions are different among the main pathological subtypes, specific aUPD regions may aid the sub-classification of breast cancer. In addition, we provide statistical support using TP53 as an example that identifying aUPD regions can be an effective approach in finding aberrant genes. We thus conclu

Cutting Through the Noise: Bacterial Chemotaxis in Marine Microenvironments

The ability of marine microbes to navigate toward chemical hotspots can determine their nutrient uptake and has the potential to affect the cycling of elements in the ocean. The link between bacterial navigation and nutrient cycling highlights the need to understand how chemotaxis functions in the context of marine microenvironments. Chemotaxis hinges on the stochastic binding/unbinding of molecules with surface receptors, the transduction of this information through an intracellular signaling cascade, and the activation and control of flagellar motors. The intrinsic randomness of these processes is a central challenge that cells must deal with in order to navigate, particularly under dilute conditions where noise and signal are similar in magnitude. Such conditions are ubiquitous in the ocean, where nutrient concentrations are often extremely low and subject to rapid variation in space (e.g., particulate matter, nutrient plumes) and time (e.g., diffusing sources, fluid mixing). Stochastic, biophysical models of chemotaxis have the potential to illuminate how bacteria cope with noise to efficiently navigate in such environments. At the same time, new technologies for experimentation allow for continuous interrogation—from milliseconds through to days—of bacterial responses in custom dynamic nutrient landscapes, providing unprecedented access to the behavior of chemotactic cells in microenvironments engineered to mimic those cells navigate in the wild. These recent theoretical and experimental developments have created an opportunity to derive population-level uptake from single-cell motility characteristics in ways that could inform the next generation of marine biogeochemical cycling models.ISSN:2296-774

Basin-scale biogeography of Prochlorococcus and SAR11 ecotype replication

Establishing links between microbial diversity and environmental processes requires resolving the high degree of functional variation among closely related lineages or ecotypes. Here, we implement and validate an improved metagenomic approach that estimates the spatial biogeography and environmental regulation of ecotype-specific replication patterns (RObs) across ocean regions. A total of 719 metagenomes were analyzed from meridional Bio-GO-SHIP sections in the Atlantic and Indian Ocean. Accounting for sequencing bias and anchoring replication estimates in genome structure were critical for identifying physiologically relevant biological signals. For example, ecotypes within the dominant marine cyanobacteria Prochlorococcus exhibited distinct diel cycles in RObs that peaked between 19:00-22:00. Additionally, both Prochlorococcus ecotypes and ecotypes within the highly abundant heterotroph Pelagibacter (SAR11) demonstrated systematic biogeographies in RObs that differed from spatial patterns in relative abundance. Finally, RObs was significantly regulated by nutrient stress and temperature, and explained by differences in the genomic potential for nutrient transport, energy production, cell wall structure, and replication. Our results suggest that our new approach to estimating replication is reflective of gross population growth. Moreover, this work reveals that the interaction between adaptation and environmental change drives systematic variability in replication patterns across ocean basins that is ecotype-specific, adding an activity-based dimension to our understanding of microbial niche space