Critical mutation rate has an exponential dependence on population size for eukaryotic-length genomes with crossover

The critical mutation rate (CMR) determines the shift between survival-of-the-fittest and survival of individuals with greater mutational robustness (“flattest”). We identify an inverse relationship between CMR and sequence length in an in silico system with a two-peak fitness landscape; CMR decreases to no more than five orders of magnitude above estimates of eukaryotic per base mutation rate. We confirm the CMR reduces exponentially at low population sizes, irrespective of peak radius and distance, and increases with the number of genetic crossovers. We also identify an inverse relationship between CMR and the number of genes, confirming that, for a similar number of genes to that for the plant Arabidopsis thaliana (25,000), the CMR is close to its known wild-type mutation rate; mutation rates for additional organisms were also found to be within one order of magnitude of the CMR. This is the first time such a simulation model has been assigned input and produced output within range for a given biological organism. The decrease in CMR with population size previously observed is maintained; there is potential for the model to influence understanding of populations undergoing bottleneck, stress, and conservation strategy for populations near extinction

Environmental pleiotropy and demographic history direct adaptation under antibiotic selection

Evolutionary rescue following environmental change requires mutations permitting population growth in the new environment. If change is severe enough to prevent most of the population reproducing, rescue becomes reliant on mutations already present. If change is sustained, the fitness effects in both environments, and how they are associated—termed ‘environmental pleiotropy’—may determine which alleles are ultimately favoured. A population’s demographic history—its size over time—influences the variation present. Although demographic history is known to affect the probability of evolutionary rescue, how it interacts with environmental pleiotropy during severe and sustained environmental change remains unexplored. Here, we demonstrate how these factors interact during antibiotic resistance evolution, a key example of evolutionary rescue fuelled by pre-existing mutations with pleiotropic fitness effects. We combine published data with novel simulations to characterise environmental pleiotropy and its effects on resistance evolution under different demographic histories. Comparisons among resistance alleles typically revealed no correlation for fitness—i.e., neutral pleiotropy—above and below the sensitive strain’s minimum inhibitory concentration. Resistance allele frequency following experimental evolution showed opposing correlations with their fitness effects in the presence and absence of antibiotic. Simulations demonstrated that effects of environmental pleiotropy on allele frequencies depended on demographic history. At the population level, the major influence of environmental pleiotropy was on mean fitness, rather than the probability of evolutionary rescue or diversity. Our work suggests that determining both environmental pleiotropy and demographic history is critical for predicting resistance evolution, and we discuss the practicalities of this during in vivo evolution

Opposing effects of final population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis-SIM) and decrease at high final population density (density-associated mutation-rate plasticity-DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 10  cells ml ). These findings demonstrate a strikingly close and nuanced relationship of ecological factors-stress and population density-with mutation, the fuel of all evolution

Roadmap Towards Communitywide Intercalibration and Standardization of Ocean Nucleic Acids ‘Omics Measurements

In January 2020, the US Ocean Carbon & Biogeochemistry (OCB) Project Office funded the Ocean Nucleic Acids 'omics Intercalibration and Standardization workshop held at the University of North Carolina in Chapel Hill. Thirty-two participants from across the US, along with guests from Canada and France, met to develop a framework for standardization and intercalibration (S&I) of ocean nucleic acid ‘omics (na’omics) approaches (i.e., amplicon sequencing, metagenomics and metatranscriptomics). During the three-day workshop, participants discussed numerous topics, including: a) sample biomass collection and nucleic acid preservation for downstream analysis, b) extraction protocols for nucleic acids, c) addition of standard reference material to nucleic acid isolation protocols, d) isolation methods unique to RNA, e) sequence library construction, and f ) integration of bioinformatic considerations. This report provides a summary of these and other topics covered during the workshop and a series of recommendations for future S&I activities for na’omics approaches.The Ocean Nucleic Acids ‘Omics Intercalibration and Standardization Workshop was supported by grants from the Ocean Carbon & Biogeochemistry Program (OCB) – funding provided by the National Science Foundation (NSF) and the National Aeronautics and Space Administration (NASA) – and the Simons Foundation. This report was developed with federal support of NSF (OCE-1558412) and NASA (NNX17AB17G)

A Multi-Wavelength Mass Analysis of RCS2 J232727.6-020437, a ~3x1015^{15}M⊙_{\odot} Galaxy Cluster at z=0.7

We present an initial study of the mass and evolutionary state of a massive and distant cluster, RCS2 J232727.6-020437. This cluster, at z=0.6986, is the richest cluster discovered in the RCS2 project. The mass measurements presented in this paper are derived from all possible mass proxies: X-ray measurements, weak-lensing shear, strong lensing, Sunyaev Zel'dovich effect decrement, the velocity distribution of cluster member galaxies, and galaxy richness. While each of these observables probe the mass of the cluster at a different radius, they all indicate that RCS2 J232727.6-020437 is among the most massive clusters at this redshift, with an estimated mass of M_200 ~3 x10^15 h^-1 Msun. In this paper, we demonstrate that the various observables are all reasonably consistent with each other to within their uncertainties. RCS2 J232727.6-020437 appears to be well relaxed -- with circular and concentric X-ray isophotes, with a cool core, and no indication of significant substructure in extensive galaxy velocity data.Comment: 19 pages, 15 figures, submitted to ApJ on March 5, 2015; in press. Manuscript revised following the referee revie

Spontaneous mutation rate is a plastic trait associated with population density across domains of life

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Core handling and processing for the WAIS Divide ice-core project

On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed

Core handling and processing for the WAIS Divide ice-core project

On 1 December 2011 the West Antarctic Ice Sheet (WAIS) Divide ice-core project reached its final depth of 3405 m. The WAIS Divide ice core is not only the longest US ice core to date, but is also the highest-quality deep ice core, including ice from the brittle ice zone, that the US has ever recovered. The methods used at WAIS Divide to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the US National Ice Core Laboratory (NICL) and the methods used to process and sample the ice at the NICL are described and discussed