Fitness Is Strongly Influenced by Rare Mutations of Large Effect in a Microbial Mutation Accumulation Experiment

Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect.     

Comprehensive DNA microarray expression profiles of tumors in tenascin-C-knockout mice

Tenascin-C (TNC), an extracellular matrix glycoprotein, plays a pivotal role in tumor growth. However, the mechanism whereby TNC affects tumor biology remains unclear. To investigate the exact role of TNC in primary tumor growth, a mouse mammary tumor cell line, GLMT1, was first developed. Subsequently, global gene expression in GLMT1-derived tumors was compared between wild-type (WT) and TNC-knockout (TNKO) mice. Tumors in WT mice were significantly larger than those in TNKO mice. DNA microarray analysis revealed 447 up and 667 downregulated in the tumors inoculated into TNKO mice as compared to tumors in WT mice. Validation by quantitative gene expression analysis showed that Tnc, Cxcl1, Cxcl2, and Cxcr2 were significantly upregulated in WT mice. We hypothesize that TNC stimulates the CXCL1/2-CXCR2 pathway involved in cancer cell proliferation.     

Selection analysis on the rapid evolution of a secondary sexual trait

Evolutionary analyses of population translocations (experimental or accidental) have been important in demonstrating speed of evolution because they subject organisms to abrupt environmental changes that create an episode of selection. However, the strength of selection in such studies is rarely measured, limiting our understanding of the evolutionary process. This contrasts with long-term, mark–recapture studies of unmanipulated populations that measure selection directly, yet rarely reveal evolutionary change. Here, we present a study of experimental evolution of male colour in Trinidadian guppies where we tracked both evolutionary change and individual-based measures of selection. Guppies were translocated from a predator-rich to a low-predation environment within the same stream system. We used a combination of common garden experiments and monthly sampling of individuals to measure the phenotypic and genetic divergence of male coloration between ancestral and derived fish. Results show rapid evolutionary increases in orange coloration in both populations (1 year or three generations), replicating the results of previous studies. Unlike previous studies, we linked this evolution to an individual-based analysis of selection. By quantifying individual reproductive success and survival, we show, for the first time, that males with more orange and black pigment have higher reproductive success, but males with more black pigment also have higher risk of mortality. The net effect of selection is thus an advantage of orange but not black coloration, as reflected in the evolutionary response. This highlights the importance of considering all components of fitness when understanding the evolution of sexually selected traits in the wild.     

How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH₂ or NADH determines radical formation. During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing—asymptotically—with fatty acid length to 0.5, when compared with 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH₂ in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings.     

Patch assessment in foraging flocks of European starlings: evidence for the use of public information

A field experiment was carried out to determine whether group-foragingstarlings (Sturnus vulgaris) use public information to helpthem estimate the quality of an artificial resource patch anddepart accordingly. Three kinds of information are potentiallyavailable in a group: patch-sample information, pre-harvestinformation, and public information. These three types of informationcan be combined into four patch assessment strategies: (1) patch-samplealone; (2) patch-sample and pre-harvest; (3) patch-sample andpublic; and (4) patch-sample, pre-harvest, and public. Dependingon the foraging environment we presented to the starlings, eachassessment strategy made a unique set of predictions concerningthe patch departure decisions of pairs of birds based on differencesin their foraging success. The environment was manipulated intwo ways: by altering the variability in patch quality and bychanging compatibility, the ease with which individual birdscould simultaneously acquire both patch-sample and public information.Our observations on patch persistence and departure order demonstratethat the starlings used a combination of patch-sample and publicinformation, but not pre-harvest information, to estimate thequality of the experimental patch. Moreover, our results suggestthat starlings use public information only when it is easilyavailable and ignore it under incompatible conditions. Thisstudy provides the first evidence of public information usein a patch assessment problem.     

Investigating structure and temporal scale in social organizations using identified individuals

Studies of individually identified animals can produce substantialdata sets containing information on the structure and temporalscale of social organizations. However, methods of analyzingsuch data are not well established. Important features of asocial organization are revealed by plotting the rate of persistenceof the associations between pairs of individuals over a rangeof time lags (lagged association rate). The consistency of long-termrelationships can be characterized using the rate of associationof pairs of individuals between their first and last observedassociations (intermediate association rate). A hierarchicalseries of models featuring exponentially decaying lagged associationrates may be fitted to these data. This technique retrievedthe essential parameters of five simulated social organizationsand, when used on real data, portrayed the essential featuresof the patterns of temporal change in relationships betweenanimals. The method should be especially useful for analyzingfissionfusion societies containing 10–10, 000 individuallyidentifiable animals.     

WFS1 and non-syndromic low-frequency sensorineural hearing loss: A novel mutation in a Portuguese case

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin.     

Change of liver metabolism of 1,2-dibromoethane during simultaneous treatment with carbon tetrachloride

The combination of carbon tetrachloride (CCl₄) and 1,2-dibromoethane (DBE) in isolated rat hepatocytes led to a significant potentiation of both lipid peroxidation and of plasma membrane damage observed after a single treatment with CCl₄. Such a synergistic effect appeared to be related to the CCl₄-induced shift of DBE metabolism from the cytosolic conjugation with glutathione towards the microsomal transformation into toxic intermediates. In fact, CCl₄ significantly inactivated hepatocyte total GSH-transferase, i.e. the DBE detoxification pathway. Furthermore, while the microsomal metabolism of CCl₄ was not affected by the simultaneous presence of DBE, the amount of DBE reactive metabolities covalently bound to hepatocyte protein was significantly enhanced in the presence of CCl₄.     

Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells

Acetylcholine synthesis from radiolabelled glucose was monitored in cerebral cortex cells isolated from brains of suckling and adult rats. Acetylcholine synthesis was found much higher in suckling animals, both in the absence and presence of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) inhibitor, paraoxon. Together with choline (20 μM), carnitine was found to stimulate acetylcholine synthesis in a synergistic way in cortex cells from adult rats (18%). Choline, however, was incapable of reversing an inhibitory effect exerted by carnitine on acetylcholine synthesis in cortex cells from suckling animals. Distribution of carnitine derivatives was found significantly different in the cells from young and old animals, the content of acetylcarnitine decreased with age with a corresponding increase of free carnitine. The observed differences in carnitine effect on acetylcholine synthesis suggested that high acetylcarnitine in cells capable of β-oxidation might be correlated with the lower level of acetylcholine synthesis.     

Thiosulfinate Tolerance Is a Virulence Strategy of an Atypical Bacterial Pathogen of Onion

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