Spontaneous Mutations Decrease Sensitivity of Gene Expression to Random Environmental Variation in Caenorhabditis elegans

Biological phenotypes are described as “canalized” if they are robust to minor variation of environment and/or genetic background. The existence of a robust phenotype logically implies that some underlying mechanism must be variable, in the sense of “able to vary”, in order to compensate for variation in the environment and/or genetic effects. Several lines of evidence lead to the conclusion that deleterious mutations predictably render morphological, developmental, and life-history traits more sensitive to small random environmental perturbations - that is, mutations de-canalize the phenotype. and the common (unmutated) ancestor. There was significantly less environmental variance in the MA lines than in the ancestor, both among replicates of the same gene and among genes.Deleterious mutations consistently decrease the within-line component of variance in transcript abundance, which is straightforwardly interpreted as reducing the sensitivity of gene expression to small random variation in the environment. This finding is consistent with the idea that underlying variability in gene expression might be mechanistically responsible for phenotypic robustness

Comparative Genomic Analysis of 130 Bacteriophages Infecting Bacteria in the Genus Pseudomonas

Bacteria of the genus Pseudomonas are genetically diverse and ubiquitous in the environment. Like other bacteria, those of the genus Pseudomonas are susceptible to bacteriophages which can significantly affect their host in many ways, ranging from cell lysis to major changes in morphology and virulence. Insights into phage genomes, evolution, and functional relationships with their hosts have the potential to contribute to a broader understanding of Pseudomonas biology, and the development of novel phage therapy strategies. Here we provide a broad-based comparative and evolutionary analysis of 130 complete Pseudomonas phage genome sequences available in online databases. We discovered extensive variation in genome size (ranging from 3 to 316 kb), G + C percentage (ranging from 37 to 66%), and overall gene content (ranging from 81–96% of genome space). Based on overall nucleotide similarity and the numbers of shared gene products, 100 out of 130 genome sequences were grouped into 12 different clusters; 30 were characterized as singletons, which do not have close relationships with other phage genomes. For 5/12 clusters, constituent phage members originated from two or more different Pseudomonas host species, suggesting that phage in these clusters can traverse bacterial species boundaries. An analysis of CRISPR spacers in Pseudomonas bacterial genome sequences supported this finding. Substantial diversity was revealed in analyses of phage gene families; out of 4,462 total families, the largest had only 39 members and there were 2,992 families with only one member. An evolutionary analysis of 72 phage gene families, based on patterns of nucleotide diversity at non-synonymous and synonymous sites, revealed strong and consistent signals for purifying selection. Our study revealed highly diverse and dynamic Pseudomonas phage genomes, and evidence for a dominant role of purifying selection in shaping the evolution of genes encoded in them

Endogenous ROS Levels in C. Elegans Under Exogenous Stress Support Revision of Oxidative Stress Theory of Life-History Tradeoffs

Background: The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Results: Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments–consistent with the oxidative stress theory of aging. Conclusions: Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory

Paternal Mitochondrial Transmission in Intra-Species \u3ci\u3eCaenorhabditis briggsae\u3c/i\u3e Hybrids

To study mitochondrial-nuclear genetic interactions in the nematode Caenorhabditis briggsae, our three laboratories independently created 38 intra-species cytoplasmic-nuclear hybrid (cybrid) lines. Although the cross design combines maternal mitotypes with paternal nuclear genotypes, eight lines (21%) unexpectedly contained paternal mitotypes. All eight share in common ancestry of one of two genetically related strains. This unexpected parallel observation of paternal mitochondrial transmission, undesirable given our intent of creating cybrids, provides a serendipitous experimental model and framework to study the molecular and evolutionary basis of uniparental mitochondrial inheritance

Genome-wide polymorphism and signatures of selection in the symbiotic sea anemone Aiptasia

Background: Coral reef ecosystems are declining in response to global climate change and anthropogenic impacts. Yet patterns of standing genetic variation within cnidarian species, a major determinant of adaptive potential, are virtually unknown at genome-scale resolution. We explore patterns of genome-wide polymorphism and identify candidate loci under selection in the sea anemone Aiptasia, an important laboratory model system for studying the symbiosis between corals and dinoflagellate algae of the genus Symbiodinium. Results: Low coverage genome sequencing revealed large genetic distances among globally widespread lineages, novel candidate targets of selection, and considerably higher heterozygosity than previously reported for Aiptasia. More than 670,000 single nucleotide polymorphisms were identified among 10 Aiptasia individuals including two pairs of genetic clones. Evolutionary relationships based on genome-wide polymorphism supported the current paradigm of a genetically distinct population from the US South Atlantic that harbors diverse Symbiodinium clades. However, anemones from the US South Atlantic demonstrated a striking lack of shared derived polymorphism. Heterozygosity was an important feature shaping nucleotide diversity patterns: at any given SNP site, more than a third of individuals genotyped were heterozygotes, and heterozygosity within individual genomes ranged from 0.37–0.58 %. Analysis of nonsynonymous and synonymous sites suggested that highly heterozygous regions are evolving under relaxed purifying selection compared to the rest of the Aiptasia genome. Genes previously identified as having elevated evolutionary rates in Aiptasia compared to other cnidarians were found in our study to be under strong purifying selection within Aiptasia. Candidate targets of selection, including lectins and genes involved in Rho GTPase signalling, were identified based on unusual signatures of nucleotide diversity, Tajima’s D, and heterozygosity compared to genome-wide averages. Conclusions: This study represents the first genome-wide analysis of Tajima’s D in a cnidarian. Our results shed light on patterns of intraspecific genome-wide polymorphism in a model for studies of coral-algae symbiosis and present genetic targets for future research on evolutionary and cellular processes in early-diverging metazoans.Keywords: heterozygosity, Cnidarian symbiosis, genome skimming, Symbiodinium, Tajima's

Evolution Of A Higher Intracellular Oxidizing Environment In Caenorhabditis Elegans Under Relaxed Selection

We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutation-accumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (DM) of these measures of oxidative stress are similar to those reported for fitness-related traits. Conversely, there is no significant relationship between either marker of oxidative stress and the per-generation frequencies of base substitution or GC-TA transversion. Although these results provide no direct evidence for a causative relationship between oxidative damage and base substitution mutations, to the extent that oxidative damage may be weakly mutagenic in the germline, the case for condition-dependent mutation is advanced

Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs

BACKGROUND: The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. RESULTS: Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments–consistent with the oxidative stress theory of aging. CONCLUSIONS: Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory.Keywords: Aging, Lifespan, Fitness, Free radicals, Resource allocatio