In Pursuit of Safety: One-Hundred Years of Toxicological Risk Assessment

The publication in 1962 of Rachel Carson's Silent Spring marks the mid-point in a century that saw, in its first half, the emergence of public health concerns related to human exposures to chemicals, and, in its second half, the emergence of public policies to deal with those concerns. Those policies made it imperative that the scientific community come to grips with the problem of identifying exposure levels not likely to cause harm. This problem was not significantly discussed within the scientific community until the 1950s, and well-described methods for practical solutions to it did not appear until the 1970s. An important report from the National Academy of Sciences, published in 1983 (Risk Assessment in the Federal Government), provided an analysis of these emerging methods, and recommended a useful framework for the assessment and management of risk. This framework remains central to public health and regulatory decision-making. A high-level perspective is offered on events leading to and following the 1983 report. The article describes early thinking about chemical toxicity and the scientific path that thinking followed through the 20th century, and to the present.     

DNA microenvironments and the molecular clock

Summary A few years ago we presented a stationary Markov model of gene evolution according to which only homologous genes from not too divergent species obeying the condition of being stationary may behave as reliable molecular clocks. A compartmentalized model of the nuclear genome in which the genes are distributed in compartments, the isochores, defined by their G+C content has been proposed recently. We have found that only homologous gene pairs that are stationary, and belong to the same isochore, can be used consistently for the determination of phylogeny and base substitution rate. In particular, for the rodent-human couple, only about half of the homologous gene pairs are stationary. Stationary genes evolve at the third silent codon position with the same velocity independent of the genes and base composition. By contrast, nonstationary genes display apparent rate values (pseudovelocities) that are significantly higher. Our results cast doubt upon recent claims of a large acceleration in the rate of molecular evolution in rodents.     

Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents

Summary Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.     

Contrasting rates of nucleotide substitution in the X-Linked and Y-Linked zinc finger genes

We have sequenced the entire exon (1,180 bp) encoding the zinc finger domain of the X-linked and Y-linked zinc finger genes (ZFX and ZFY, respectively) in the orangutan, the baboon, the squirrel monkey, and the rat; a total of 9,442 by were sequenced. The ratio of the rates of synonymous substitution in the ZFY and ZFX genes is estimated to be 2.1 in primates. This is close to the ratio of 2.3 estimated from primate ZFY and ZFX intron sequences and supports the view that the male-to-female ratio of mutation rate in humans is considerably higher than 1 but not extremely large. The ratio of synonymous substitution rates in ZFY and ZFX is estimated to be 1.3 in the rat lineage but 4.2 in the mouse lineage. The former is close to the estimate (1.4) from introns. The much higher ratio in the mouse lineage (not statistically significant) might have arisen from relaxation of selective constraints. The synonymous divergence between mouse and rat ZFX is considerably lower than that between mouse and rat autosomal genes, agreeing with previous observations and providing some evidence for stronger selective constraints on synonymous changes in X-linked genes than in autosomal genes. At the protein level ZFX has been highly conserved in all placental mammals studied while ZFY has been well conserved in primates and foxes but has evolved rapidly in mice and rats, possibly due to relaxation of functional constraints as a result of the development of X-inactivation of ZFX in rodents. The long persistence of the ZFY-ZFX gene pair in mammals provides some insight into the process of degeneration of Y-linked genes.Correspondence to: W.-H. Li     

A multivariate approach to the selection of biological reserves

Multivariate analysis provides an effective context for the examination of some significant aspects of biodiversity and conservation. The framework is a multidimensional space that integrates sample sites, taxa and environments. This approach enables terms such as representativeness, complementarity and irreplaceability to be integrated within an intuitive and practical framework for reserve design. Cluster analysis is proposed to determine what is there by defining a set of complementary clusters. These clusters are sampled in a representative manner; from the core outward. The degree of irreplaceability of a site is defined as the multivariate distance of each potential reserve site to its nearest neighbour.     

Both facilitation and limiting similarity shape the species coexistence in dry alkali grasslands

Facilitation is an important driver of community assembly, and often overwhelms the effect of competition in stressed habitats. Thus, net effect of biotic interactions is often positive in stressed grasslands, where dominant species and litter can protect the subordinate species. Besides facilitation, niche partitioning can also support species coexistence leading to limiting similarity between subordinate species. Our aim was to provide a detailed analysis of fine-scale biotic interactions in stressed alkali grasslands. We supposed, that there are positive relationships between the main biomass fractions and species richness. We expected the expansion of trait ranges and the increase of trait dissimilarity with increasing biomass scores (total litter, green biomass of dominant species) and species richness. We studied the relationships between main biomass fractions, species richness, functional diversity and functional trait indices (ranges, weighted means and Rao indices). We used fine-scale biomass sampling in nine stands of dry alkali grasslands dominated by Festuca pseudovina. The detected relationships were always positive between the main biomass fractions (green biomass of dominant species, total litter and green biomass of subordinate species) and species richness. We found that the green biomass of dominant species and total litter increased ranges and dissimilarity of functional traits. Our results suggest that in dry alkali grasslands facilitation is crucial in shaping vegetation composition. The green biomass of dominant species and total litter increased the biomass production of subordinate species leading to overyielding. We found that mechanisms of facilitation and limiting similarity were jointly shaping the species coexistence in stressed grasslands, such as alkali grasslands.     

Soil fauna diversity increases CO2 but suppresses N2O emissions from soil

Soil faunal activity can be a major control of greenhouse gas (GHG) emissions from soil. Effects of single faunal species, genera or families have been investigated, but it is unknown how soil fauna diversity may influence emissions of both carbon dioxide (CO₂, end product of decomposition of organic matter) and nitrous oxide (N₂O, an intermediate product of N transformation processes, in particular denitrification). Here, we studied how CO₂ and N₂O emissions are affected by species and species mixtures of up to eight species of detritivorous/fungivorous soil fauna from four different taxonomic groups (earthworms, potworms, mites, springtails) using a microcosm set‐up. We found that higher species richness and increased functional dissimilarity of species mixtures led to increased faunal‐induced CO₂ emission (up to 10%), but decreased N₂O emission (up to 62%). Large ecosystem engineers such as earthworms were key drivers of both CO₂ and N₂O emissions. Interestingly, increased biodiversity of other soil fauna in the presence of earthworms decreased faunal‐induced N₂O emission despite enhanced C cycling. We conclude that higher soil fauna functional diversity enhanced the intensity of belowground processes, leading to more complete litter decomposition and increased CO₂ emission, but concurrently also resulting in more complete denitrification and reduced N₂O emission. Our results suggest that increased soil fauna species diversity has the potential to mitigate emissions of N₂O from soil ecosystems. Given the loss of soil biodiversity in managed soils, our findings call for adoption of management practices that enhance soil biodiversity and stimulate a functionally diverse faunal community to reduce N₂O emissions from managed soils.     

Fungal communities living within leaves of native Hawaiian dicots are structured by landscape‐scale variables as well as by host plants

A phylogenetically diverse array of fungi live within healthy leaf tissue of dicotyledonous plants. Many studies have examined these endophytes within a single plant species and/or at small spatial scales, but landscape‐scale variables that determine their community composition are not well understood, either across geographic space, across climatic conditions, or in the context of host plant phylogeny. Here, we evaluate the contributions of these variables to endophyte beta diversity using a survey of foliar endophytic fungi in native Hawaiian dicots sampled across the Hawaiian archipelago. We used Illumina technology to sequence fungal ITS1 amplicons to characterize foliar endophyte communities across five islands and 80 host plant genera. We found that communities of foliar endophytic fungi showed strong geographic structuring between distances of 7 and 36 km. Endophyte community structure was most strongly associated with host plant phylogeny and evapotranspiration, and was also significantly associated with NDVI, elevation and solar radiation. Additionally, our bipartite network analysis revealed that the five islands we sampled each harboured significantly specialized endophyte communities. These results demonstrate how the interaction of factors at large and small spatial and phylogenetic scales shapes fungal symbiont communities.