Gene expression can accelerate ecological divergence by rapidly tweaking the response of an organism to novel environments, with more divergent environments exerting stronger selection and, supposedly, requiring faster adaptive responses. Organisms adapted to extreme environments provide ideal systems to test this hypothesis, particularly when compared to related species with milder ecological niches. The Emperor penguin (Aptenodytes forsteri) is the only warm-blooded vertebrate breeding in the harsh Antarctic winter, in stark contrast with the less cold-adapted sister species, the King penguin (A. patagonicus). Assembling the first de novo transcriptomes and analysing multi-tissue (brain, kidney, liver, muscle, skin) RNAseq data from natural populations of both species, we quantified the shifts in tissue-enhanced genes, co-expression gene networks, and differentially expressed genes characterising Emperor penguin adaptation to extreme Antarctic ecology. Our analyses revealed the crucial role played by muscle and liver in temperature homeostasis, fasting and whole-body energy metabolism (glucose/insulin regulation, lipid metabolism, fatty acid beta-oxidation, and blood coagulation). Repatterning at the regulatory level appears as more important in the brain of the Emperor penguin, showing the lowest signature of differential gene expression but the largest co-expression gene network shift. Nevertheless, over-expressed genes related to mTOR signalling in the brain and the liver support their central role in cold and fasting responses. Besides contributing to understanding the genetics underlying complex traits, like body energy reservoir management, our results provide a first insight into the role of gene expression in adaptation to one of the most extreme environmental conditions endured by an endotherm. less

Sedentary lifestyles, mismatched with our active foraging history, contribute to escalating rates of non-communicable diseases. Contemporary hunter-gatherers appear to be highly active, but little is known about physical activity levels in hunter-gatherer children. We analysed 150 days of accelerometer data from 51 BaYaka hunter-gatherer children (aged 3-18) in the Republic of Congo, comparing it with British and American children (MCS and NHANES). BaYaka children were highly active, engaging in over 3 hours of moderate-to-vigorous physical activity (MVPA) daily, surpassing British adolescents by over 70 minutes. In US children activity declined with age; while in BaYaka children activity increased with age, unaffected by gender. Reflecting their foraging lifestyle, activity patterns varied within and between days, yet all children consistently rose with the sun. These findings highlight the impact of a foraging upbringing on children\'s activity levels, providing a benchmark for understanding childhood physical activity and wellbeing. less

CRISPR-Cas9 gene drives (CCGDs) are powerful tools for genetic control of wild populations, useful for eradication of disease vectors, conservation of endangered species and other applications. However, Cas9 alone and in a complex with gRNA can cause double-stranded DNA breaks at off-target sites, which could increase the mutational load and lead to loss of heterozygosity (LOH). These undesired effects raise potential concerns about the long-term evolutionary safety of CCGDs, but the magnitude of these effects is unknown. To estimate how the presence of a CCGD or a Cas9 alone in the genome affects the rates of LOH events and de novo mutations, we carried out a mutation accumulation experiment in yeast Saccharomyces cerevisiae. Despite its substantial statistical power, our experiment revealed no detectable effect of CCGD or Cas9 alone on the genome-wide rates of mutations or LOH events, suggesting that these rates are affected by less than 30%. Nevertheless, we found that Cas9 caused a slight but significant shift towards more interstitial and fewer terminal LOH events, and the CCGD caused a significant difference in the distribution of LOH events on Chromosome V. Taken together, our results show that these genetic elements impose a weak and likely localized additional mutational burden in the yeast model. Although the mutagenic effects of CCGDs need to be further evaluated in other systems, our results suggest that the effect of CCGDs on off-target mutation rates and genetic diversity may be acceptable. less

Recent studies suggest that elevated temperatures interact with nutrition to exacerbate the negative effects of poor nutrition. Furthermore, populations adapted to distinct environments differ in their sensitivity to combined thermal and nutritional stress. However, most studies have tested these effects using constant temperatures, even though animals in the wild experience daily and seasonal thermal fluctuations. Here, we used two locally-adapted populations of D. melanogaster from the east coast of Australia (a tropical and a temperate population) to ask whether temperature fluctuations interact with nutrition in the same manner as constant temperature conditions to shape life history traits, and how this differs across populations. We found that fluctuating temperatures exacerbate the negative effects of a poor diet when compared to constant temperatures. Moreover, the negative effects of nutritional stress were significantly greater in the tropical population. In contrast, we found that the temperate population was able to utilize nutrition in unique ways to maintain optimal viability under warmer temperatures. Our findings reveal the ways in which temperature and nutrition interact to impact key life history traits in geographically distinct populations, while also highlighting the importance of using temperature assays representative of natural diel cycles when examining insect responses to climate change. less

In combination therapy, bacteria are challenged with two or more antibiotics simultaneously. Ideally, separate mutations are required to adapt to each of them, which is a priori expected to hinder the evolution of full resistance. Yet, the success of this strategy ultimately depends on how well the combination controls the growth of bacteria with and without resistance mutations. To design a combination treatment, we need to choose drugs and their doses and decide how many drugs get mixed. Which combinations are good? To answer this question, we set up a stochastic pharmacodynamic model and determine the probability to successfully eradicate a bacterial population. We consider bacteriostatic and two types of bactericidal drugs -- those that kill independent of replication and those that kill during replication. To establish results for a null model, we consider non-interacting drugs and implement the two most common models for drug independence -- Loewe additivity and Bliss independence. Our results show that combination therapy is almost always better in limiting the evolution of resistance than administering just one drug, even though we keep the total drug dose constant for a \'fair\' comparison. Yet, exceptions exist for drugs with steep dose-response curves. Combining a bacteriostatic and a bactericidal drug which can kill non-replicating cells is particularly beneficial. Our results suggest that a 50:50 drug ratio -- even if not always optimal -- is usually a good and safe choice. Applying three or four drugs is beneficial for treatment of strains with large mutation rates but adding more drugs otherwise only provides a marginal benefit or even a disadvantage. By systematically addressing key elements of treatment design, our study provides a basis for future models which take further factors into account. It also highlights conceptual challenges with translating the traditional concepts of drug independence to the single-cell level. less

Although several filoviruses are dangerous human pathogens, there is conflicting evidence regarding their origins and interactions with animal hosts. Here we attempt to improve this understanding using the paleoviral record over a geological time scale, protein structure predictions, tests for evolutionary maintenance, and phylogenetic methods that alleviate sources of bias and error. We found evidence for long branch attraction bias in the L gene tree for filoviruses, and that using codon-specific models and protein structural comparisons of paleoviruses ameliorated conflict and bias. We found evidence for four ancient filoviral groups, each with extant viruses and paleoviruses with open reading frames. Furthermore, we found evidence of repeated transfers of filovirus-like elements to mouse-like rodents. A filovirus-like nucleoprotein ortholog with an open reading frame was detected in three subfamilies of spalacid rodents (present since the Miocene). These elements were unique among the detected filovirus-like paleoviruses in possessing open reading frames, expression products, and evidence for purifying selection. Our finding of structural conservation over geological time for paleoviruses informs virus and paleovirus discovery methods. Our results resolve a deep conflict in the evolutionary framework for filoviruses and reveal that genomic transfers to vertebrate hosts with potentially functional co-options have been more widespread than previously appreciated. less

In the wild, any population is likely to be spatially structured. Whereas we deeply understand evolutionary dynamics in well-mixed populations, our understanding of evolutionary dynamics in subdivided populations needs to be improved. In this work, I quantify the impact of genotype-dependent gene flow on the evolutionary dynamics of a subdivided population. Specifically, I build a model of a population structured as the island or the stepping stone model in which genotype-dependent gene flow is represented by individuals migrating between its sub-populations at a rate depending on their genotype. I analytically calculate the fixation probability and time of a mutation arising in the subdivided population under the low migration limit, which I validate with numerical simulations. I find that the island and the stepping stone models lead to the same fixation probability. Moreover, comparing the fixation probability in these models to the one in a well-mixed population of the same total census size allows me to identify an effective selection coefficient and population size. In the island and the stepping stone models, the effective selection coefficient differs from the selection coefficient if the wild-type and the mutant migration rates are different, whereas the effective population size equals the total census size. Finally, I show that genotype-dependent gene flow increases the fixation time, which allows for distinguishing the island and the stepping stone models, as opposed to the fixation probability. less

Fisheries-induced mortality is size-selective, commonly targeting large individuals, which leads to evolution towards smaller size and early maturation. However, little is known on whether behaviour is affected. Here we aimed at testing whether size-dependent harvest indirectly affects behavioural traits that might have ecological consequences. Specifically, we assessed feeding rate (which affects prey abundance), boldness (which determines a fish vulnerability to predators), and sociability, which determines how a fish interacts with conspecifics and ultimately affects foraging and predation avoidance. In addition, we tested whether the differences in behaviour were associated to differences in selected key genes expression, to understand its molecular regulation. With a decade-long selection experiment on guppies Poecilia reticulata, we created populations with life histories adapted to positively size-dependent harvest, i.e., like that induced by fishing (fast life history). For comparison, we also created populations adapted to the opposite size-selection, and populations experiencing no size-selection. Fish exposed to positively size-dependent harvest were bolder, more likely to feed, were more social/aggressive, and expressed less brain avt (arginine vasotocin) relative to those exposed to negatively size-dependent harvest. In addition, higher expression of th and th2 (tyrosine hydroxylase 1 and 2), and neuroD2 (neuronal differentiation factor 2) were linked with bolder behaviour and higher feeding in normal (no-threat) conditions, while higher avt, th, and neuroD2 were associated with higher sociability/aggression after a threat. Fish exposed to positively size-dependent harvest presented behaviours linked to faster life histories as theoretically expected. Therefore, harvest selection does not only affect fish size and life history, but indirectly leads to boldness and higher feeding rates, which potentially results in higher vulnerability to predators and higher pressure on prey abundance, respectively. Our results suggest that size-dependent mortality have further consequences to the ecosystem, beyond the target species. less

Predicting population responses to environmental changes requires understanding interactions among environmentally induced phenotypic variation, selection, demography and genetic variation, and thereby predicting eco-evolutionary dynamics emerging across diverse temporal and spatial scales. Partially migratory metapopulations (PMMPs), featuring seasonal coexistence of resident and migrant individuals across multiple spatially distinct subpopulations, have clear potential for complex spatio-seasonal eco-evolutionary dynamics through impacts of selection on migration on spatial population dynamics, and feedbacks resulting from ongoing micro-evolution. However, the key genetic and environmental conditions that maintain migratory polymorphisms, and eco-evolutionary dynamics of PMMPs under stochastic environmental variation and strong seasonal perturbations, have not yet been resolved. Accordingly, we present a general individual-based model that tracks eco-evolutionary dynamics in PMMPs inhabiting spatially structured, seasonally varying landscapes, with migration formulated as a quantitative genetic threshold trait. Our simulations show that such genetic and landscape structures, which commonly occur in nature, can readily produce a variety of stable partially migratory systems given diverse regimes of spatio-seasonal environmental variation. Typically, partial migration is maintained whenever sites differ in non-breeding season suitability resulting from variation in density-dependence, causing \'ideal free\' non-breeding distributions where residents and migrants occur with frequencies that generate similar survival probabilities. Yet, stable partial migration can also arise without any fixed differences in non-breeding season density-dependence among sites, and even without density-dependence at all, through risk-spreading given sufficiently large stochastic environmental fluctuations among sites and years. Finally, we show that local non-breeding season mortality events, as could result from extreme climatic events, can generate eco-evolutionary dynamics that ripple out to affect breeding and non-breeding season space use of subpopulations throughout the PMMP, on both short and longer timeframes. Such effects result from spatially divergent selection on both the occurrence and destinations of migration. Our model thus shows how facultative seasonal migration can act as a key mediator of eco-evolutionary dynamics in spatially and seasonally structured environments, providing key steps towards predicting responses of natural partially migratory populations to ongoing changes in spatio-seasonal patterns of environmental variation. less

The molecular hitchhiking model proposes that linked non-coding regions also undergo fixation, while fixing a beneficial allele in a population. This concept can be applied to identify loci with functional and evolutionary significance. Putative circumsporozoite protein (CSP) in Plasmodium vivax (PvpuCSP) identified following the molecular hitchhiking model, holds evolutionary significance. We investigated the extent of genetic polymorphism in PvpuCSP and the role of natural selection which shapes the genetic composition and maintains the diversity in P. vivax isolates from India. Sequencing the putative CSP of P. vivax (PvpuCSP) in 71 isolates revealed a well-conserved N- and C-terminal, constituting around 80% of the gene. PCR amplification and sequencing validated extensive diversity in the repeat region, ranging from 1.8 to 2.2 kb towards the C-terminal, identifying 37 different alleles from 71 samples. The recent and exclusive accumulation of repeats in puCSP within P. vivax highlights its highly variable length polymorphism, making it a potential marker for estimating diversity and infection complexity. Episodic diversifying selection in the PvpuCSP repeat region, evidenced by statistically significant p-values and likelihood ratios, enhances amino acid diversity at various phylogenetic levels, facilitating adaptation for accommodating different substrates for degradation. less