Development and selective grain make plasticity 'take the lead' in adaptive evolution.

BACKGROUND: Biological evolution exhibits an extraordinary capability to adapt organisms to their environments. The explanation for this often takes for granted that random genetic variation produces at least some beneficial phenotypic variation in which natural selection can act. Such genetic evolvability could itself be a product of evolution, but it is widely acknowledged that the immediate selective gains of evolvability are small on short timescales. So how do biological systems come to exhibit such extraordinary capacity to evolve? One suggestion is that adaptive phenotypic plasticity makes genetic evolution find adaptations faster. However, the need to explain the origin of adaptive plasticity puts genetic evolution back in the driving seat, and genetic evolvability remains unexplained. RESULTS: To better understand the interaction between plasticity and genetic evolvability, we simulate the evolution of phenotypes produced by gene-regulation network-based models of development. First, we show that the phenotypic variation resulting from genetic and environmental perturbation are highly concordant. This is because phenotypic variation, regardless of its cause, occurs within the relatively specific space of possibilities allowed by development. Second, we show that selection for genetic evolvability results in the evolution of adaptive plasticity and vice versa. This linkage is essentially symmetric but, unlike genetic evolvability, the selective gains of plasticity are often substantial on short, including within-lifetime, timescales. Accordingly, we show that selection for phenotypic plasticity can be effective in promoting the evolution of high genetic evolvability. CONCLUSIONS: Without overlooking the fact that adaptive plasticity is itself a product of genetic evolution, we show how past selection for plasticity can exercise a disproportionate effect on genetic evolvability and, in turn, influence the course of adaptive evolution.

Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial.

The specific effects of administering live probiotics in the human gut are not well characterized. To this end, we investigated the immediate effect of Lactobacillus rhamnosus GG (LGG) in the jejunum of 27 healthy volunteers 2 h after ingestion using a combination of global RNA sequencing of human biopsies and bacterial DNA sequencing in a multi-visit, randomized, cross-over design (ClinicalTrials.gov number NCT03140878). While LGG was detectable in jejunum after 2 h in treated subjects, the gene expression response vs. placebo was subtle if assessed across all subjects. However, clustering analysis revealed that one-third of subjects exhibited a strong and consistent LGG response involving hundreds of genes, where genes related to B cell activation were upregulated, consistent with prior results in mice. Immunohistochemistry and single cell-based deconvolution analyses showed that this B cell signature likely is due to activation and proliferation of existing B cells rather than B cell immigration to the tissue. Our results indicate that the LGG strain has an immediate effect in the human gut in a subpopulation of individuals. In extension, our data strongly suggest that studies on in vivo probiotic effects in humans require large cohorts and must take individual variation into account.

Sex biased expression and co-expression networks in development, using the hymenopteran Nasonia vitripennis.

Sexual dimorphism requires regulation of gene expression in developing organisms. These developmental differences are caused by differential expression of genes and isoforms. The effect of expressing a gene is also influenced by which other genes are simultaneously expressed (functional interactions). However, few studies have described how these processes change across development. We compare the dynamics of differential expression, isoform switching and functional interactions in the sexual development of the model parasitoid wasp Nasonia vitripennis, a system that permits genome wide analysis of sex bias from early embryos to adults. We find relatively little sex-bias in embryos and larvae at the gene level, but several sub-networks show sex-biased functional interactions in early developmental stages. These networks provide new candidates for hymenopteran sex determination, including histone modification. In contrast, sex-bias in pupae and adults is driven by the differential expression of genes. We observe sex-biased isoform switching consistently across development, but mostly in genes that are already differentially expressed. Finally, we discover that sex-biased networks are enriched by genes specific to the Nasonia clade, and that those genes possess the topological properties of key regulators. These findings suggest that regulators in sex-biased networks evolve more rapidly than regulators of other developmental networks.

Developmental plasticity and evolutionary explanations.

Developmental plasticity looks like a promising bridge between ecological and developmental perspectives on evolution. Yet, there is no consensus on whether plasticity is part of the explanation for adaptive evolution or an optional "add-on" to genes and natural selection. Here, we suggest that these differences in opinion are caused by differences in the simplifying assumptions, and particular idealizations, that enable evolutionary explanation. We outline why idealizations designed to explain evolution through natural selection prevent an understanding of the role of development, and vice versa. We show that representing plasticity as a reaction norm conforms with the idealizations of selective explanations, which can give the false impression that plasticity has no explanatory power for adaptive evolution. Finally, we use examples to illustrate why evolutionary explanations that include developmental plasticity may in fact be more satisfactory than explanations that solely refer to genes and natural selection.

How adaptive plasticity evolves when selected against.

Adaptive plasticity allows organisms to cope with environmental change, thereby increasing the population's long-term fitness. However, individual selection can only compare the fitness of individuals within each generation: if the environment changes more slowly than the generation time (i.e., a coarse-grained environment) a population will not experience selection for plasticity even if it is adaptive in the long-term. How does adaptive plasticity then evolve? One explanation is that, if competing alleles conferring different degrees of plasticity persist across multiple environments, natural selection between genetic lineages could select for adaptive plasticity (lineage selection). We show that adaptive plasticity can evolve even in the absence of such lineage selection. Instead, we propose that adaptive plasticity in coarse-grained environments evolves as a by-product of inefficient short-term natural selection: populations that rapidly evolve their phenotypes in response to selective pressures follow short-term optima, with the result that they have reduced long-term fitness across environments. Conversely, populations that accumulate limited genetic change within each environment evolve long-term adaptive plasticity even when plasticity incurs short-term costs. These results remain qualitatively similar regardless of whether we decrease the efficiency of natural selection by increasing the rate of environmental change or decreasing mutation rate, demonstrating that both factors act via the same mechanism. We demonstrate how this mechanism can be understood through the concept of learning rate. Our work shows how plastic responses that are costly in the short term, yet adaptive in the long term, can evolve as a by-product of inefficient short-term selection, without selection for plasticity at either the individual or lineage level.

Developmental plasticity in reptiles: Insights from temperature-dependent gene expression in wall lizard embryos.

Many features of the development of reptiles are affected by temperature, but very little is known about how incubation temperature affects gene expression. Here, we provide a detailed case study of gene expression profiles in common wall lizard (Podarcis muralis) embryos developing at stressfully low (15°C) versus benign (24°C) temperature. For maximum comparability between the two temperature regimes, we selected a precise developmental stage early in embryogenesis defined by the number of somites. We used a split-clutch design and lizards from four different populations to evaluate the robustness of temperature-responsive gene expression profiles. Embryos incubated at stressfully low incubation temperature expressed on average 20% less total RNA than those incubated at benign temperatures, presumably reflecting lower rates of transcription at cool temperature. After normalizing for differences in total amounts of input RNA, we find that approximately 50% of all transcripts show significant expression differences between the two incubation temperatures. Transcripts with the most extreme changes in expression profiles are associated with transcriptional and translational regulation and chromatin remodeling, suggesting possible epigenetic mechanisms underlying acclimation of early embryos to cool temperature. We discuss our findings in light of current advances in the use of transcriptomic data to study how individuals acclimatize and populations adapt to thermal stress.

Signatures of selection in embryonic transcriptomes of lizards adapting in parallel to cool climate.

Populations adapting independently to the same environment provide important insights into the repeatability of evolution at different levels of biological organization. In the 20th century, common wall lizards (Podarcis muralis) from southern and western Europe were introduced to England, north of their native range. Nonnative populations of both lineages have adapted to the shorter season and lower egg incubation temperature by increasing the absolute rate of embryonic development. Here, we tested if this adaptation is accompanied by signatures of directional selection in the transcriptomes of early embryos and, if so, if nonnative populations show adaptive convergence. Embryos from nonnative populations exhibited gene expression profiles consistent with directional selection following introduction, but different genes were affected in the two lineages. Despite this, the functional enrichment of genes that changed their expression following introduction showed substantial similarity between lineages, and was consistent with mechanisms that should promote developmental rate. Moreover, the divergence between nonnative and native populations was enriched for genes that were temperature-responsive in native populations. These results indicate that small populations are able to adapt to new climatic regimes, but the means by which they do so may largely be determined by founder effects and other sources of genetic drift.

OGS2: genome re-annotation of the jewel wasp Nasonia vitripennis.

BACKGROUND: Nasonia vitripennis is an emerging insect model system with haplodiploid genetics. It holds a key position within the insect phylogeny for comparative, evolutionary and behavioral genetic studies. The draft genomes for N. vitripennis and two sibling species were published in 2010, yet a considerable amount of transcriptiome data have since been produced thereby enabling improvements to the original (OGS1.2) annotated gene set. We describe and apply the EvidentialGene method used to produce an updated gene set (OGS2). We also carry out comparative analyses showcasing the usefulness of the revised annotated gene set. RESULTS: The revised annotation (OGS2) now consists of 24,388 genes with supporting evidence, compared to 18,850 for OGS1.2. Improvements include the nearly complete annotation of untranslated regions (UTR) for 97 % of the genes compared to 28 % of genes for OGS1.2. The fraction of RNA-Seq validated introns also grow from 85 to 98 % in this latest gene set. The EST and RNA-Seq expression data provide support for several non-protein coding loci and 7712 alternative transcripts for 4146 genes. Notably, we report 180 alternative transcripts for the gene lola. Nasonia now has among the most complete insect gene set; only 27 conserved single copy orthologs in arthropods are missing from OGS2. Its genome also contains 2.1-fold more duplicated genes and 1.4-fold more single copy genes than the Drosophila melanogaster genome. The Nasonia gene count is larger than those of other sequenced hymenopteran species, owing both to improvements in the genome annotation and to unique genes in the wasp lineage. We identify 1008 genes and 171 gene families that deviate significantly from other hymenopterans in their rates of protein evolution and duplication history, respectively. We also provide an analysis of alternative splicing that reveals that genes with no annotated isoforms are characterized by shorter transcripts, fewer introns, faster protein evolution and higher probabilities of duplication than genes having alternative transcripts. CONCLUSIONS: Genome-wide expression data greatly improves the annotation of the N. vitripennis genome, by increasing the gene count, reducing the number of missing genes and providing more comprehensive data on splicing and gene structure. The improved gene set identifies lineage-specific genomic features tied to Nasonia's biology, as well as numerous novel genes. OGS2 and its associated search tools are available at http://arthropods.eugenes.org/EvidentialGene/nasonia/ , www.hymenopteragenome.org/nasonia/ and waspAtlas: www.tinyURL.com/waspAtlas . The EvidentialGene pipeline is available at https://sourceforge.net/projects/evidentialgene/ .

Function and evolution of DNA methylation in Nasonia vitripennis.

The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5' regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5' and 3' UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression patterns. We speculate that loss of methylation may result in increased developmental specialization in evolution and acquisition of methylation may lead to broader constitutive expression.

Introduction pathway and climate trump ecology and life history as predictors of establishment success in alien frogs and toads.

A major goal for ecology and evolution is to understand how abiotic and biotic factors shape patterns of biological diversity. Here, we show that variation in establishment success of nonnative frogs and toads is primarily explained by variation in introduction pathways and climatic similarity between the native range and introduction locality, with minor contributions from phylogeny, species ecology, and life history. This finding contrasts with recent evidence that particular species characteristics promote evolutionary range expansion and reduce the probability of extinction in native populations of amphibians, emphasizing how different mechanisms may shape species distributions on different temporal and spatial scales. We suggest that contemporary changes in the distribution of amphibians will be primarily determined by human-mediated extinctions and movement of species within climatic envelopes, and less by species-typical traits.