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Uncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges. Individuals with different genotypes may respond differently to environmental variation. Here, Favé et al. find substantial impacts of different environment exposures on the transcriptome and clinical endophenotypes when controlling for genetic ancestry by analyzing data from ∼1000 individuals from a founder population in Quebec.

The EAGLE algorithm and software identifies replicable gene-by-environment interactions based on associations between environment and allele-specific expression. Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on associations between environmental variables and allele-specific expression. Combining whole-blood RNA-seq with extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared with only four using standard GxE interaction testing. EAGLE provides new opportunities for researchers to identify GxE interactions using functional genomic data.

The origin of complex worker-caste systems in ants perplexed Darwin 1 and has remained an enduring problem for evolutionary and developmental biology 2 – 6 . Ants originated approximately 150 million years ago, and produce colonies with winged queen and male castes as well as a wingless worker caste 7 . In the hyperdiverse genus Pheidole , the wingless worker caste has evolved into two morphologically distinct subcastes—small-headed minor workers and large-headed soldiers 8 . The wings of queens and males develop from populations of cells in larvae that are called wing imaginal discs 7 . Although minor workers and soldiers are wingless, vestiges or rudiments of wing imaginal discs appear transiently during soldier development 7 , 9 – 11 . Such rudimentary traits are phylogenetically widespread and are primarily used as evidence of common descent, yet their functional importance remains equivocal 1 , 12 – 14 . Here we show that the growth of rudimentary wing discs is necessary for regulating allometry—disproportionate scaling—between head and body size to generate large-headed soldiers in the genus Pheidole . We also show that Pheidole colonies have evolved the capacity to socially regulate the growth of rudimentary wing discs to control worker subcaste determination, which allows these colonies to maintain the ratio of minor workers to soldiers. Finally, we provide comparative and experimental evidence that suggests that rudimentary wing discs have facilitated the parallel evolution of complex worker-caste systems across the ants. More generally, rudimentary organs may unexpectedly acquire novel regulatory functions during development to facilitate adaptive evolution. In the ant genus Pheidole the growth of rudimentary wing discs—which influence developmental allometry to produce castes with distinct morphologies—is socially regulated to determine the worker-to-soldier ratio in Pheidole colonies.

Aims/hypothesisType 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk.MethodsWe developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study.ResultsThe model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years.Conclusions/interpretationThis novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Background A fundamental and enduring problem in evolutionary biology is to understand how populations differentiate in the wild, yet little is known about what role organismal development plays in this process. Organismal development integrates environmental inputs with the action of gene regulatory networks to generate the phenotype. Core developmental gene networks have been highly conserved for millions of years across all animals, and therefore, organismal development may bias variation available for selection to work on. Biased variation may facilitate repeatable phenotypic responses when exposed to similar environmental inputs and ecological changes. To gain a more complete understanding of population differentiation in the wild, we integrated evolutionary developmental biology with population genetics, morphology, paleoecology and ecology. This integration was made possible by studying how populations of the ant species Monomorium emersoni respond to climatic and ecological changes across five ‘Sky Islands’ in Arizona, which are mountain ranges separated by vast ‘seas’ of desert. Sky Islands represent a replicated natural experiment allowing us to determine how repeatable is the response of M. emersoni populations to climate and ecological changes at the phenotypic, developmental, and gene network levels. Results We show that a core developmental gene network and its phenotype has kept pace with ecological and climate change on each Sky Island over the last ∼90,000 years before present (BP). This response has produced two types of evolutionary change within an ant species: one type is unpredictable and contingent on the pattern of isolation of Sky lsland populations by climate warming, resulting in slight changes in gene expression, organ growth, and morphology. The other type is predictable and deterministic, resulting in the repeated evolution of a novel wingless queen phenotype and its underlying gene network in response to habitat changes induced by climate warming. Conclusion Our findings reveal dynamics of developmental gene network evolution in wild populations. This holds important implications: (1) for understanding how phenotypic novelty is generated in the wild; (2) for providing a possible bridge between micro- and macroevolution; and (3) for understanding how development mediates the response of organisms to past, and potentially, future climate change.

The originally diverse ciscoe fish fauna of the Laurentian Great Lakes has suffered many extinctions and local extirpations. Bloaters (Coregonus hoyi) are presumed extirpated from Lake Ontario and the reintroduction of this deepwater fish is under consideration. Given the demographic fluctuations of this species in the other Great Lakes and its recent intralacustrine origin, we sought to identify a genetically diverse and similar source of C. hoyi via an analysis of genetic diversity and population structure using 10 microsatellite loci. Despite well-documented demographic declines, we found no genetic evidence of bottlenecks in 12 C. hoyi samples from the four potential donor lakes (Huron, Michigan, Superior and Nipigon). By contrast, evidence of bottlenecks in historical samples of C. artedi from Lake Ontario suggested that standard genetic methods frequently used to identify population bottlenecks can only detect very severe and long-lasting demographic declines in naturally large populations. Patterns of genetic differentiation and assignment tests indicated that C. hoyi from Lake Huron and Lake Michigan, which are not differentiated, are genetically most similar to Lake Ontario ciscoes. The small available sample of deepwater ciscoes recently caught in Lake Ontario did not allow determining if these represent a small undetected C. hoyi population or a recent invasion of the deep section by C. artedi. On the basis of genetic criteria, we conclude that C. hoyi from any location within Lake Huron or Lake Michigan would be judicious sources of breeders for reintroducing C. hoyi in Lake Ontario.

Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses.

We report the draft genome sequence of the red harvester ant, Pogonomyrmex barbatus. The genome was sequenced using 454 pyrosequencing, and the current assembly and annotation were completed in less than 1 y. Analyses of conserved gene groups (more than 1,200 manually annotated genes to date) suggest a high-quality assembly and annotation comparable to recently sequenced insect genomes using Sanger sequencing. The red harvester ant is a model for studying reproductive division of labor, phenotypic plasticity, and sociogenomics. Although the genome of P. barbatus is similar to other sequenced hymenopterans (Apis mellifera and Nasonia vitripennis) in GC content and compositional organization, and possesses a complete CpG methylation toolkit, its predicted genomic CpG content differs markedly from the other hymenopterans. Gene networks involved in generating key differences between the queen and worker castes (e.g., wings and ovaries) show signatures of increased methylation and suggest that ants and bees may have independently co-opted the same gene regulatory mechanisms for reproductive division of labor. Gene family expansions (e.g., 344 functional odorant receptors) and pseudogene accumulation in chemoreception and P450 genes compared with A. mellifera and N. vitripennis are consistent with major life-history changes during the adaptive radiation of Pogonomyrmex spp., perhaps in parallel with the development of the North American deserts.

A Correction to this paper has been published: https://doi.org/10.1007/s00125-021-05544-x

Reintroduction programs aim at reinstalling a self-sustained population into the wild via a period of supplementation with captive-bred individuals. This procedure can rapidly generate inbreeding among offspring because of the mating scheme and this inbreeding might be further enhanced by the reintroduction scenario. First, we used simulations to assess the consequences of breeding designs on mean inbreeding index F among offspring when the genetic diversity of breeders, the number and sex ratios of breeders, and the proportion of successful crosses vary. A high number of breeders, a balanced sex ratio, a high proportion of effective crosses and a genetically diverse source population generally contribute to lower F values. However, moderately high (>=20) numbers of breeders combined with all but the most biased sex ratios produced mean F values near minimal values. The variability in F was negligible in all parameter combinations except for a very small number of breeders (5) and very biased sex ratios (<= 1M : 19F). We also simulated the long-term inbreeding dynamics in the introduced population under various demographic scenarios. Our main finding was that the annual number of introduced offspring is a decisive factor in establishing long-term F values in the supplemented population. Low supplementation levels (10²) quickly generated an almost completely inbred population whereas high levels (>=10⁴) produced stable F values close to that of the introduced offspring. Simulations were run based on the life history and specific demographics of the bloater (Coregonus hoyi), whose reintroduction in Lake Ontario is being considered.