386 research outputs found
The maintenance of sex in bacteria is ensured by its potential to reload genes
Why sex is maintained in nature is a fundamental question in biology. Natural
genetic transformation (NGT) is a sexual process by which bacteria actively
take up exogenous DNA and use it to replace homologous chromosomal sequences.
As it has been demonstrated, the role of NGT in repairing deleterious mutations
under constant selection is insufficient for its survival, and the lack of
other viable explanations have left no alternative except that DNA uptake
provides nucleotides for food. Here we develop a novel simulation approach for
the long-term dynamics of genome organization (involving the loss and
acquisition of genes) in a bacterial species consisting of a large number of
spatially distinct populations subject to independently fluctuating ecological
conditions. Our results show that in the presence of weak inter-population
migration NGT is able to subsist as a mechanism to reload locally lost,
intermittently selected genes from the collective gene pool of the species
through DNA uptake from migrants. Reloading genes and combining them with those
in locally adapted genomes allow individual cells to re-adapt faster to
environmental changes. The machinery of transformation survives under a wide
range of model parameters readily encompassing real-world biological
conditions. These findings imply that the primary role of NGT is not to serve
the cell with food, but to provide homologous sequences for restoring genes
that have disappeared from or become degraded in the local population.Comment: 16 pages with 3 color figures. Manuscript accepted for publication in
Genetics (www.genetics.org
Relative time constraints improve molecular dating
Dating the tree of life is central to understanding the evolution of life on Earth. Molecular clocks calibrated with fossils represent the state of the art for inferring the ages of major groups. Yet, other information on the timing of species diversification can be used to date the tree of life. This is the case for instance for horizontal gene transfer events and ancient coevolutionary relationships such as (endo)symbioses, which can imply temporal relationships between two nodes in a phylogeny (Davín et al. 2018). This can be particularly helpful when the geological record is sparse, e.g. for microorganisms, which represent the vast majority of extant and extinct biodiversity
Congruent evolution of genetic and environmental robustness in microRNA
Genetic robustness, the preservation of an optimal phenotype in the face of
mutations, is critical to the understanding of evolution as phenotypically
expressed genetic variation is the fuel of natural selection. The origin of
genetic robustness, whether it evolves directly by natural selection or it is a
correlated byproduct of other phenotypic traits, is, however, unresolved.
Examining microRNA (miRNA) genes of several eukaryotic species, Borenstein and
Ruppin (Borenstein et al. 2006, PNAS 103: 6593), showed that the structure of
miRNA precursor stem-loops exhibits significantly increased mutational
robustness in comparison with a sample of random RNA sequences with the same
stem-loop structure. The observed robustness was found to be uncorrelated with
traditional measures of environmental robustness -- implying that miRNA
sequences show evidence of the direct evolution of genetic robustness. These
findings are surprising as theoretical results indicate that the direct
evolution of robustness requires high mutation rates and/or large effective
population sizes only found among RNA viruses, not multicellular eukaryotes.
Introducing a novel measure of environmental robustness based on the
equilibrium thermodynamic ensemble of secondary structures of the miRNA
precursor sequences we demonstrate that the biophysics of RNA folding, induces
a high level of correlation between genetic (mutational) and environmental
(thermodynamic) robustness, as expected from the theory of plastogenetic
congruence introduced by Ancel and Fontana (Ancel et al. 2000, J. Exp. Zool.
288: 242). In light of theoretical considerations we believe that this
correlation strongly suggests that genetic robustness observed in miRNA
sequences is the byproduct of selection for environmental robustness.Comment: Accepted for publication in Mol. Biol. Evol. Supplemental Information
available as a separate pdf file from
http://angel.elte.hu:/~ssolo/miRNA_supp_mat.pd
Bacterial microevolution and the Pangenome
The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history
Genome size evolution in the Archaea
What determines variation in genome size, gene content and genetic diversity at the broadest scales across the tree of life? Much of the existing work contrasts eukaryotes with prokaryotes, the latter represented mainly by Bacteria. But any general theory of genome evolution must also account for the Archaea, a diverse and ecologically important group of prokaryotes that represent one of the primary domains of cellular life. Here, we survey the extant diversity of Bacteria and Archaea, and ask whether the general principles of genome evolution deduced from the study of Bacteria and eukaryotes also apply to the archaeal domain. Although Bacteria and Archaea share a common prokaryotic genome architecture, the extant diversity of Bacteria appears to be much higher than that of Archaea. Compared with Archaea, Bacteria also show much greater genome-level specialisation to specific ecological niches, including parasitism and endosymbiosis. The reasons for these differences in long-term diversification rates are unclear, but might be related to fundamental differences in informational processing machineries and cell biological features that may favour archaeal diversification in harsher or more energy-limited environments. Finally, phylogenomic analyses suggest that the first Archaea were anaerobic autotrophs that evolved on the early Earth
Optimal tumor sampling for immunostaining of biomarkers in breast carcinoma
IntroductionBiomarkers, such as Estrogen Receptor, are used to determine therapy and prognosis in breast carcinoma. Immunostaining assays of biomarker expression have a high rate of inaccuracy; for example, estimates are as high as 20% for Estrogen Receptor. Biomarkers have been shown to be heterogeneously expressed in breast tumors and this heterogeneity may contribute to the inaccuracy of immunostaining assays. Currently, no evidence-based standards exist for the amount of tumor that must be sampled in order to correct for biomarker heterogeneity. The aim of this study was to determine the optimal number of 20X fields that are necessary to estimate a representative measurement of expression in a whole tissue section for selected biomarkers: ER, HER-2, AKT, ERK, S6K1, GAPDH, Cytokeratin, and MAP-Tau.MethodsTwo collections of whole tissue sections of breast carcinoma were immunostained for biomarkers. Expression was quantified using the Automated Quantitative Analysis (AQUA) method of quantitative immunofluorescence. Simulated sampling of various numbers of fields (ranging from one to thirty five) was performed for each marker. The optimal number was selected for each marker via resampling techniques and minimization of prediction error over an independent test set.ResultsThe optimal number of 20X fields varied by biomarker, ranging between three to fourteen fields. More heterogeneous markers, such as MAP-Tau protein, required a larger sample of 20X fields to produce representative measurement.ConclusionsThe optimal number of 20X fields that must be sampled to produce a representative measurement of biomarker expression varies by marker with more heterogeneous markers requiring a larger number. The clinical implication of these findings is that breast biopsies consisting of a small number of fields may be inadequate to represent whole tumor biomarker expression for many markers. Additionally, for biomarkers newly introduced into clinical use, especially if therapeutic response is dictated by level of expression, the optimal size of tissue sample must be determined on a marker-by-marker basis
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