Lethal mutagenesis and evolutionary epidemiology

The lethal mutagenesis hypothesis states that within-host populations of pathogens can be driven to extinction when the load of deleterious mutations is artificially increased with a mutagen, and becomes too high for the population to be maintained. Although chemical mutagens have been shown to lead to important reductions in viral titres for a wide variety of RNA viruses, the theoretical underpinnings of this process are still not clearly established. A few recent models sought to describe lethal mutagenesis but they often relied on restrictive assumptions. We extend this earlier work in two novel directions. First, we derive the dynamics of the genetic load in a multivariate Gaussian fitness landscape akin to classical quantitative genetics models. This fitness landscape yields a continuous distribution of mutation effects on fitness, ranging from deleterious to beneficial (i.e. compensatory) mutations. We also include an additional class of lethal mutations. Second, we couple this evolutionary model with an epidemiological model accounting for the within-host dynamics of the pathogen. We derive the epidemiological and evolutionary equilibrium of the system. At this equilibrium, the density of the pathogen is expected to decrease linearly with the genomic mutation rate U. We also provide a simple expression for the critical mutation rate leading to extinction. Stochastic simulations show that these predictions are accurate for a broad range of parameter values. As they depend on a small set of measurable epidemiological and evolutionary parameters, we used available information on several viruses to make quantitative and testable predictions on critical mutation rates. In the light of this model, we discuss the feasibility of lethal mutagenesis as an efficient therapeutic strategy.     

Lifting the veil on the correction of double counting incidents in hybrid life cycle assessment

Life cycle assessment (LCA) and environmentally extended input–output analyses (EEIOA) are two techniques commonly used to assess environmental impacts of an activity/product. Their strengths and weaknesses are complementary, and they are thus regularly combined to obtain hybrid LCAs. A number of approaches in hybrid LCA exist, which leads to different results. One of the differences is the method used to ensure that mixed LCA and EEIOA data do not overlap, which is referred to as correction for double counting. This aspect of hybrid LCA is often ignored in reports of hybrid assessments and no comprehensive study has been carried out on it. This article strives to list, compare, and analyze the different existing methods for the correction of double counting. We first harmonize the definitions of the existing correction methods and express them in a common notation, before introducing a streamlined variant. We then compare their respective assumptions and limitations. We discuss the loss of specific information regarding the studied activity/product and the loss of coherent financial representation caused by some of the correction methods. This analysis clarifies which techniques are most applicable to different tasks, from hybridizing individual LCA processes to integrating complete databases. We finally conclude by giving recommendations for future hybrid analyses.     

Sampling strategy optimization to increase statistical power in landscape genomics: A simulation‐based approach

An increasing number of studies are using landscape genomics to investigate local adaptation in wild and domestic populations. Implementation of this approach requires the sampling phase to consider the complexity of environmental settings and the burden of logistical constraints. These important aspects are often underestimated in the literature dedicated to sampling strategies. In this study, we computed simulated genomic data sets to run against actual environmental data in order to trial landscape genomics experiments under distinct sampling strategies. These strategies differed by design approach (to enhance environmental and/or geographical representativeness at study sites), number of sampling locations and sample sizes. We then evaluated how these elements affected statistical performances (power and false discoveries) under two antithetical demographic scenarios. Our results highlight the importance of selecting an appropriate sample size, which should be modified based on the demographic characteristics of the studied population. For species with limited dispersal, sample sizes above 200 units are generally sufficient to detect most adaptive signals, while in random mating populations this threshold should be increased to 400 units. Furthermore, we describe a design approach that maximizes both environmental and geographical representativeness of sampling sites and show how it systematically outperforms random or regular sampling schemes. Finally, we show that although having more sampling locations (between 40 and 50 sites) increase statistical power and reduce false discovery rate, similar results can be achieved with a moderate number of sites (20 sites). Overall, this study provides valuable guidelines for optimizing sampling strategies for landscape genomics experiments.     

Paternity tests support a diallelic self‐incompatibility system in a wild olive (Olea europaea subsp. laperrinei,Oleaceae)

Self‐incompatibility (SI) is the main mechanism that favors outcrossing in plants. By limiting compatible matings, SI interferes in fruit production and breeding of new cultivars. In the Oleeae tribe (Oleaceae), an unusual diallelic SI system (DSI) has been proposed for three distantly related species including the olive (Olea europaea), but empirical evidence has remained controversial for this latter. The olive domestication is a complex process with multiple origins. As a consequence, the mixing of S‐alleles from two distinct taxa, the possible artificial selection of self‐compatible mutants and the large phenological variation of blooming may constitute obstacles for deciphering SI in olive. Here, we investigate cross‐genotype compatibilities in the Saharan wild olive (O. e. subsp. laperrinei). As this taxon was geographically isolated for thousands of years, SI should not be affected by human selection. A population of 37 mature individuals maintained in a collection was investigated. Several embryos per mother were genotyped with microsatellites in order to identify compatible fathers that contributed to fertilization. While the pollination was limited by distance inside the collection, our results strongly support the DSI hypothesis, and all individuals were assigned to two incompatibility groups (G1 and G2). No self‐fertilization was observed in our conditions. In contrast, crosses between full or half siblings were frequent (ca. 45%), which is likely due to a nonrandom assortment of related trees in the collection. Finally, implications of our results for orchard management and the conservation of olive genetic resources are discussed.     

First partial cranium of Togocetus from Kpogamé (Togo) and the protocetid diversity in the Togolese phosphate basin

Earliest cetaceans (whales) originated from the early Eocene of Indo-Pakistan, but the group dispersed through most of the oceans of the planet by the late middle to late Eocene. This late Eocene global distribution indicates that important dispersal events took place during the middle Eocene (Lutetian), a globally undersampled time interval that is well documented in the Togolese phosphate series. We report here the first discovery of a partial cetacean cranium from middle Eocene deposits of Togo (West Africa). A 3D model of the cranium and teeth was reconstructed in order to reveal hidden anatomical features. The dental and cranial characteristics of the Togolese specimen recall those of protocetid taxa described in Africa, Asia, and North America, but also display significant differences. In particular, we show that the new specimen shares a number of morphological features with the Togolese taxon Togocetus. Such a hypothesis is further supported by a cladistic analysis including 45 taxa and 167 morphological characters, which recovers the new specimen close to Togocetus as the first offshoot of protocetids. Phylogenetic analysis including all the protocetids remains of Kpogamé confirms the singular diversity of the Togolese phosphate basin, and enables to examine potential connections with faunas from contemporaneous localities in Africa.     

LCA and nutritional assessment of southern Benin market vegetable gardening across the production continuum

The International Journal of Life Cycle Assessment - The goal of this work is to analyse the environmental impacts across the productive continuum of market gardening in southern Benin, to...     

A Dual Strategy to Cope with High Light in Chlamydomonas reinhardtii

Absorption of light in excess of the capacity for photosynthetic electron transport is damaging to photosynthetic organisms. Several mechanisms exist to avoid photodamage, which are collectively referred to as nonphotochemical quenching. This term comprises at least two major processes. State transitions (qT) represent changes in the relative antenna sizes of photosystems II and I. High energy quenching (qE) is the increased thermal dissipation of light energy triggered by lumen acidification. To investigate the respective roles of qE and qT in photoprotection, a mutant (npq4 stt7-9) was generated in Chlamydomonas reinhardtii by crossing the state transition–deficient mutant (stt7-9) with a strain having a largely reduced qE capacity (npq4). The comparative phenotypic analysis of the wild type, single mutants, and double mutants reveals that both state transitions and qE are induced by high light. Moreover, the double mutant exhibits an increased photosensitivity with respect to the single mutants and the wild type. Therefore, we suggest that besides qE, state transitions also play a photoprotective role during high light acclimation of the cells, most likely by decreasing hydrogen peroxide production. These results are discussed in terms of the relative photoprotective benefit related to thermal dissipation of excess light and/or to the physical displacement of antennas from photosystem II.     

Acute Hypoxemia Does Not Increase the Oxidative Stress in Resting and Contracting Muscle in Humans

In healthy humans sustaining static handgrip at 60% of maximal voluntary contraction (MVC) until exhaustion, we measured the venous blood concentration of reduced ascorbic acid (RAA) and thiobarbituric acid reactive substances (TBARS), respectively, used as markers of the post-exercise oxidative stress and lipid peroxidation. Measurements were conducted in normoxemia, then during a 30-min period of hypoxemia (PaO 2 =56 mmHg) produced by inhalation of an hypoxic gas mixture. Compared to normoxemia, hypoxemia did not significantly modify the resting concentrations of TBARS and RAA, and did not affect the consumption of ascorbic acid after 60% MVC but suppressed the post-exercise TBARS increase. We conclude that acute hypoxemia does not modify the production of oxygen free radicals after strenuous static efforts and even seems to attenuate the lipid peroxidation.