Impact of Epistasis and Pleiotropy on Evolutionary Adaptation

Evolutionary adaptation is often likened to climbing a hill or peak. While this process is simple for fitness landscapes where mutations are independent, the interaction between mutations (epistasis) as well as mutations at loci that affect more than one trait (pleiotropy) are crucial in complex and realistic fitness landscapes. We investigate the impact of epistasis and pleiotropy on adaptive evolution by studying the evolution of a population of asexual haploid organisms (haplotypes) in a model of N interacting loci, where each locus interacts with K other loci. We use a quantitative measure of the magnitude of epistatic interactions between substitutions, and find that it is an increasing function of K. When haplotypes adapt at high mutation rates, more epistatic pairs of substitutions are observed on the line of descent than expected. The highest fitness is attained in landscapes with an intermediate amount of ruggedness that balance the higher fitness potential of interacting genes with their concomitant decreased evolvability. Our findings imply that the synergism between loci that interact epistatically is crucial for evolving genetic modules with high fitness, while too much ruggedness stalls the adaptive process.Comment: 20 pages, 8 figures, plus 10 supporting figure

The nk model and population genetics

The nk model of fitness interactions is examined. This model has been used by previous authors to investigate the effects of fitness epistasis on substitution dynamics in molecular evolution, and to make broader claims about the importance of epistasis. To examine these claims, an infinite-allele approximation is introduced. In this limit, it is shown that the nk model is, at an appropriate level of description, formally identical to the non-epistatic House-of-Cards model--a well-studied model in theoretical population genetics. It is further shown that in many parameter regimes, the analytical results obtained from this infinite-allele approximation are very close to results from the full nk model (with a finite number of alleles per locus). The findings presented shed light on a number of previous results

The Kinematic and Spectral Ages of the Compact Radio Source CTD 93

We present a study of the kinematic and spectral ages of the Gigahertz-Peaked Spectrum (GPS) source CTD~93. Measurements of the hot spot separation over 8.5 yr show evidence of an increase. The separation rate along the source axis is 0.34$\pm0.11c$ (H$_{0}$=72 km s$^{-1}$ Mpc$^{-1}$), which results in a kinematic age of 2200$\pm$700 yr. Assuming that two hot spots are moving apart at equal speeds, we derive an advance speed of 0.17$\pm0.06c$. The radio lobe spectra show a high frequency steepening, as expected if energetic electrons lose energy by synchrotron radiation. The spectral break decreases with the distance from the hot spot in the northern component of CTD~93. This tendency is expected from the basic scenario of radio lobe evolution involving particle acceleration at the hot spots, with the radio lobes populated by high energy electrons which have leaked from the hot spots. Although a core-jet morphology for CTD~93 has previously been proposed, these results indicate that the morphology is similar to that of Compact Symmetric Object (CSO). From the spectral fits in the northern component we found a break frequency of 3.7 GHz at the edge of the lobe. The resultant spectral age is $\sim$300 yr assuming the equipartition magnetic field. This requires the advance speed of 0.26$c$, which shows a good agreement of the hot spot motion of 0.17$\pm0.06c$. Our results strongly support the hypothesis that CSOs are young radio sources.Comment: 25 pages, 19 figures, accepted for publication in Ap

Distributions of epistasis in microbes fit predictions from a fitness landscape model.

How do the fitness effects of several mutations combine? Despite its simplicity, this question is central to the understanding of multilocus evolution. Epistasis (the interaction between alleles at different loci), especially epistasis for fitness traits such as reproduction and survival, influences evolutionary predictions "almost whenever multilocus genetics matters". Yet very few models have sought to predict epistasis, and none has been empirically tested. Here we show that the distribution of epistasis can be predicted from the distribution of single mutation effects, based on a simple fitness landscape model. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli and the RNA virus vesicular stomatitis virus. Our results suggest that a simple fitness landscape model may be sufficient to quantitatively capture the complex nature of gene interactions. This model may offer a simple and widely applicable alternative to complex metabolic network models, in particular for making evolutionary predictions

Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans

Background: The accumulation of deleterious mutations can drastically reduce population mean fitness. Self-fertilization is thought to be an effective means of purging deleterious mutations. However, widespread linkage disequilibrium generated and maintained by self-fertilization is predicted to reduce the efficacy of purging when mutations are present at multiple loci. Methodology/Principal Findings: We tested the ability of self-fertilizing populations to purge deleterious mutations at multiple loci by exposing obligately self-fertilizing populations of Caenorhabditis elegans to a range of elevated mutation rates and found that mutations accumulated, as evidenced by a reduction in mean fitness, in each population. Therefore, purging in obligate selfing populations is overwhelmed by an increase in mutation rate. Surprisingly, we also found that obligate and predominantly self-fertilizing populations exposed to very high mutation rates exhibited consistently greater fitness than those subject to lesser increases in mutation rate, which contradicts the assumption that increases in mutation rate are negatively correlated with fitness. The high levels of genetic linkage inherent in self-fertilization could drive this fitness increase. Conclusions: Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. Th

Surface charging and electrostatic dust acceleration at the nucleus of comet 67P during periods of low activity

We have investigated through simulation the electrostatic charging of the nucleus of Comet 67 P/Churyumov-Gerasimenko during periods of weak outgassing activity. Specifically, we have modeled the surface potential and electric field at the surface of the nucleus during the initial Rosetta rendezvous at 3.5 AU and the release of the Philae lander at 3 AU. We have also investigated the possibility of dust acceleration and ejection above the nucleus due to electrostatic forces. Finally, we discuss these modeling results in the context of possible observations by instruments on both the Rosetta orbiter and the Philae lander

Case Report and Mini Literature Review: Anesthetic Management for Severe Peripartum Cardiomyopathy Complicated with Preeclampsia Using Sufetanil in Combined Spinal Epidural Anesthesia

Peripartum cardiomyopathy (PPCM) is a rare entity, and anesthetic management for cesarean section of a patient with this condition can be challenging. We hereby present the anesthetic management of a patient with PPCM complicated with preeclampsia scheduled for cesarean section, along with a mini review of literature. A 24 year-old primigravida with twin gestation was admitted to our hospital with severe PPCM and preeclampsia for peripartum care, which finally required a cesarean section. Preoperative optimization was done according to the goal of managing left ventricular failure. Combined spinal epidural (CSE) anaesthesia with bupivacaine and sufentanil was used for cesarean section under optimal monitoring. The surgery was completed without event or complication. Postoperative pain relief was adequate and patient required only one epidural top up with sufentanil 6 hours after operation. To the best of our knowledge there is no report in literature of the use of sufentanil as a neuraxial opioid in the anesthetic management of cesarean section in a patient with PPCM. CSE with sufentanil may be a safer and more effective alternative in such cases

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13