Evolutionary models predict potential mechanisms of escape from mutational meltdown

Mutagenic drugs are promising candidates for the treatment of various RNA virus infections. Increasing the mutation rate of the virus leads to rapid accumulation of deleterious mutation load, which is proposed to ultimately result in extinction as described by the theoretical concepts of mutational meltdown and lethal mutagenesis. However, the conditions and potential mechanisms of viral escape from the effects of mutagenic drugs have not been conceptually explored. Here we apply a computational approach to quantify the population dynamics and genetics of a population under high mutation rates and discuss the likelihood of adaptation to a mutagenic drug by means of three proposed mechanisms: (1) a proportion of “traditional” beneficial mutations that increase growth/fitness, (2) a mutation rate modifier (i.e., evolution of resistance to the mutagenic drug) that reduces the mutation rate, and (3) a modifier of the distribution of fitness effects, which either decreases or increases deleterious effects of mutations (i.e., evolution of tolerance to the mutagenic drug). We track the population dynamics and genetics of evolving populations and find that successful adaptations have to appear early to override the increasing mutational load and rescue the population from its imminent extinction. We highlight that the observed stochasticity of adaptation, especially by means of modifiers of the distribution of fitness effects, is difficult to capture in experimental trials, which may leave potential dangers of the use of mutagenic treatments unexposed

Identification and Quantitation of Flavanols and Proanthocyanidins in Foods: How Good are the Datas?

Evidence suggesting that dietary polyphenols, flavanols, and proanthocyanidins in particular offer significant cardiovascular health benefits is rapidly increasing. Accordingly, reliable and accurate methods are needed to provide qualitative and quantitative food composition data necessary for high quality epidemiological and clinical research. Measurements for flavonoids and proanthocyanidins have employed a range of analytical techniques, with various colorimetric assays still being popular for estimating total polyphenolic content in foods and other biological samples despite advances made with more sophisticated analyses. More crudely, estimations of polyphenol content as well as antioxidant activity are also reported with values relating to radical scavenging activity. High-performance liquid chromatography (HPLC) is the method of choice for quantitative analysis of individual polyphenols such as flavanols and proanthocyanidins. Qualitative information regarding proanthocyanidin structure has been determined by chemical methods such as thiolysis and by HPLC-mass spectrometry (MS) techniques at present. The lack of appropriate standards is the single most important factor that limits the aforementioned analyses. However, with ever expanding research in the arena of flavanols, proanthocyanidins, and health and the importance of their future inclusion in food composition databases, the need for standards becomes more critical. At present, sufficiently well-characterized standard material is available for selective flavanols and proanthocyanidins, and construction of at least a limited food composition database is feasible

The extinction time under mutational meltdown driven by high mutation rates.

Mutational meltdown describes an eco-evolutionary process in which the accumulation of deleterious mutations causes a fitness decline that eventually leads to the extinction of a population. Possible applications of this concept include medical treatment of RNA virus infections based on mutagenic drugs that increase the mutation rate of the pathogen. To determine the usefulness and expected success of such an antiviral treatment, estimates of the expected time to mutational meltdown are necessary. Here, we compute the extinction time of a population under high mutation rates, using both analytical approaches and stochastic simulations. Extinction is the result of three consecutive processes: (a) initial accumulation of deleterious mutations due to the increased mutation pressure; (b) consecutive loss of the fittest haplotype due to Muller's ratchet; (c) rapid population decline toward extinction. We find accurate analytical results for the mean extinction time, which show that the deleterious mutation rate has the strongest effect on the extinction time. We confirm that intermediate-sized deleterious selection coefficients minimize the extinction time. Finally, our simulations show that the variation in extinction time, given a set of parameters, is surprisingly small

One Diamictite and Two Rifts: Stratigraphy and Geochronology of the Gataga Mountain of Northern British Columbia

Neoproterozoic glacial diamictites and rift-related volcanics are preserved throughout the North American Cordillera, yet the nature and timing of both glaciation and rifting are poorly constrained. New geochronological, geochemical, and stratigraphic data from the Cryogenian Gataga volcanics and bounding units at Gataga Mountain, in the Kechika Trough of northern British Columbia, better constrain the age of these rift-related volcanics and suggest that they erupted during glaciation. At Gataga Mountain, three informal sequences are exposed; a basal quartzite, the Gataga volcanics, and an overlying mixed carbonate-siliciclastic succession. The basal quartzite is dominated by cross-bedded sandstone with an intertidal facies assemblage including bidirectional cross-stratification and mud-cracks, indicative of non-glacial deposition. The overlying Gataga volcanics are over one kilometer thick, comprising both mafic and felsic units, with volcaniclastic breccia and interbedded sedimentary units including iron formation and matrix-supported diamictite with exotic clasts. Magmatic ages in the upper Gataga volcanics span 696.2 0.2 to 690.1 0.2 Ma, and detrital zircon from the underlying non-glacial quartzite provide a maximum age constraint on the onset of glaciation \u3c735.8 0.6 Ma. We interpret interfingering beds of matrix-supported diamictite with exotic clasts within the Gataga volcanics to record sub-ice shelf sedimentation and volcanism during the Sturtian Glaciation. Although volcanic facies are consistent with eruption in a sub-ice to sub-aqueous (below ice shelf) environment, we acknowledge the difficulty of distinguishing sub-glacial from sub-aqueous explosive volcanic facies. Overlying the Gataga volcanics, a mixed carbonate-siliciclastic succession contains minor basalt flows that are geochemically distinct from the underlying volcanic rocks. Based on chemostratigraphic and lithostratigraphic similarities, we suggest that this sequence is correlative with Ediacaran strata to the north. Together, we suggest that the stratigraphy and geochemical signature of volcanic rocks at Gataga Mountain records two episodes of Neoproterozoic extensionrelated sedimentation and volcanism, the first indicated by the Cryogenian Gataga volcanics and interbedded sedimentary strata and the second by the overlying Ediacaran carbonate-siliciclastic succession with interfingering basalt

Monogenetic near-island seamounts in the Galapagos Archipelago

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 21(12), (2020): e2020GC008914, https://doi.org/10.1029/2020GC008914.Rarely have small seamounts on the flanks of hotspot derived ocean‐island volcanoes been the targets of sampling, due to sparse high‐resolution mapping near ocean islands. In the Galápagos Archipelago, for instance, sampling has primarily targeted the subaerial volcanic edifices, with only a few studies focusing on large‐volume submarine features. Sampling restricted to these large volcanic features may present a selection bias, potentially resulting in a skewed view of magmatic and source processes because mature magmatic systems support mixing and volcanic accretion that overprints early magmatic stages. We demonstrate how finer‐scale sampling of satellite seamounts surrounding the volcanic islands in the Galápagos can be used to lessen this bias and thus, better constrain the evolution of these volcanoes. Seamounts were targeted in the vicinity of Floreana and Fernandina Islands, and between Santiago and Santa Cruz. In all regions, individual seamounts are typically monogenetic, but each seamount field requires multigenerational magmatic episodes to account for their geochemical variability. This study demonstrates that in the southern and eastern regions the seamounts are characterized by greater geochemical variability than the islands they surround but all three regions have (Sr‐Nd‐He) isotopic signatures that resemble neighboring islands. Variations in seamount chemistry from alkalic to tholeiitic near Fernandina support the concept that islands along the center of the hotspot track undergo greater mean depths of melting, as predicted by plume theory. Patterns of geochemical and isotopic enrichment of seamounts within each region support fine‐scale mantle heterogeneities in the mantle plume sourcing the Galápagos hotspot.This work was carried out with funding from National Science Foundation Division of Ocean Sciences (OCE‐1634952 to V. D. Wanless, OCE‐1634685 to S. A. Soule). The authors have no competing interests to declare. We thank Sally Gibson and three anonymous reviewers for providing detailed and critical feedback on this manuscript.2021-05-0

Exploring the Law of Detrital Zircon: LA-ICP-MS and CA-TIMS Geochronology of Jurassic Forearc Strata, Cook Inlet, Alaska, USA

Uranium-lead (U-Pb) geochronology studies commonly employ the law of detrital zircon: A sedimentary rock cannot be older than its youngest zircon. This premise permits maximum depositional ages (MDAs) to be applied in chronostratigraphy, but geochronologic dates are complicated by uncertainty. We conducted laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and chemical abrasion-thermal ionization mass spectrometry (CA-TIMS) of detrital zircon in forearc strata of southern Alaska (USA) to assess the accuracy of several MDA approaches. Six samples from Middle–Upper Jurassic units are generally replete with youthful zircon and underwent three rounds of analysis: (1) LA-ICP-MS of ∼115 grains, with one date per zircon; (2) LA-ICP-MS of the ∼15 youngest grains identified in round 1, acquiring two additional dates per zircon; and (3) CA-TIMS of the ∼5 youngest grains identified by LA-ICP-MS. The youngest single-grain LA-ICP-MS dates are all younger than—and rarely overlap at 2σ uncertainty with—the CA-TIMS MDAs. The youngest kernel density estimation modes are typically several million years older than the CA-TIMS MDAs. Weighted means of round 1 dates that define the youngest statistical populations yield the best coincidence with CA-TIMS MDAs. CA-TIMS dating of the youngest zircon identified by LA-ICP-MS is indispensable for critical MDA applications, eliminating laser-induced matrix effects, mitigating and evaluating Pb loss, and resolving complexities of interpreting lower-precision, normally distributed LA-ICP-MS dates. Finally, numerous CA-TIMS MDAs in this study are younger than Bathonian(?)–Callovian and Oxfordian faunal correlations suggest, highlighting the need for additional radioisotopic constraints—including CA-TIMS MDAs—for the Middle–Late Jurassic geologic time scale

A Robust Age Model for the Cryogenian Pocatello Formation of Southeastern Idaho (Northwestern USA) from Tandem in situ and Isotope Dilution U-Pb Dating of Volcanic Tuffs and Epiclastic Detrital Zircons

Tandem in situ and isotope dilution U-Pb analysis of zircons from pyroclastic volcanic rocks and both glacial and non-glacial sedimentary strata of the Pocatello Formation (Idaho, northwestern USA) provides new age constraints on Cryogenian glaciation in the North American Cordillera. Two dacitic tuffs sampled within glacigenic strata of the lower diamictite interval of the Scout Mountain Member yield high-precision chemical abrasion isotope dilution U-Pb zircon eruption and depositional ages of 696.43 ± 0.21 and 695.17 ± 0.20 Ma. When supplemented by a new high-precision detrital zircon maximum depositional age of ≤ 670 Ma for shoreface and offshore sandstones unconformably overlying the lower diamictite, these data are consistent with correlation of the lower diamictite to the early Cryogenian (ca. 717–660 Ma) Sturtian glaciation. These 670–675 Ma zircons persist in beds above the upper diamictite and cap dolostone units, up to and including a purported “reworked fallout tuff,” which we instead conclude provides only a maximum depositional age of ≤ 673 Ma from epiclastic volcanic detritus. Rare detrital zircons as young as 658 Ma provide a maximum depositional age for the upper diamictite and overlying cap dolostone units. This new geochronological framework supports litho- and chemostratigraphic correlations of the lower and upper diamictite intervals of the Scout Mountain Member of the Pocatello Formation with the Sturtian (716–660 Ma) and Marinoan (≤ 650–635 Ma) low-latitude glaciations, respectively. The Pocatello Formation thus contains a more complete record of Cryogenian glaciations than previously postulated

Genomic impact of eukaryotic transposable elements

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Mobile DNA 3 (2012): 19, doi:10.1186/1759-8753-3-19.The third international conference on the genomic impact of eukaryotic transposable elements (TEs) was held 24 to 28 February 2012 at the Asilomar Conference Center, Pacific Grove, CA, USA. Sponsored in part by the National Institutes of Health grant 5 P41 LM006252, the goal of the conference was to bring together researchers from around the world who study the impact and mechanisms of TEs using multiple computational and experimental approaches. The meeting drew close to 170 attendees and included invited floor presentations on the biology of TEs and their genomic impact, as well as numerous talks contributed by young scientists. The workshop talks were devoted to computational analysis of TEs with additional time for discussion of unresolved issues. Also, there was ample opportunity for poster presentations and informal evening discussions. The success of the meeting reflects the important role of Repbase in comparative genomic studies, and emphasizes the need for close interactions between experimental and computational biologists in the years to come.The conference was supported in part by the National Institutes of Health grant 5 P41 LM006252

Genomic impact of eukaryotic transposable elements

Abstract The third international conference on the genomic impact of eukaryotic transposable elements (TEs) was held 24 to 28 February 2012 at the Asilomar Conference Center, Pacific Grove, CA, USA. Sponsored in part by the National Institutes of Health grant 5 P41 LM006252, the goal of the conference was to bring together researchers from around the world who study the impact and mechanisms of TEs using multiple computational and experimental approaches. The meeting drew close to 170 attendees and included invited floor presentations on the biology of TEs and their genomic impact, as well as numerous talks contributed by young scientists. The workshop talks were devoted to computational analysis of TEs with additional time for discussion of unresolved issues. Also, there was ample opportunity for poster presentations and informal evening discussions. The success of the meeting reflects the important role of Repbase in comparative genomic studies, and emphasizes the need for close interactions between experimental and computational biologists in the years to come.http://deepblue.lib.umich.edu/bitstream/2027.42/112619/1/13100_2012_Article_57.pd