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Evolution of HIV virulence in response to widespread scale up of antiretroviral therapy: a modeling study

There are global increases in the use of HIV antiretroviral therapy (ART), guided by clinical benefits of early ART initiation, and the efficacy of treatment as prevention of transmission. Separately, it has been shown theoretically and empirically that HIV virulence can evolve over time. Observed virulence levels may reflect an adaptive balance between infected lifespan and per-contact transmission rate. Critically, the potential effects of widespread ART on HIV virulence are unknown. To predict these effects, we used an agent-based stochastic model to simulate changes in HIV virulence, using set point viral load as a virulence proxy. We calibrated our epidemic model to the prevalence and incidence trends of South Africa. We repeated our analysis using a separate calibration, as a sensitivity analysis, and found that predicted impact of ART on virulence was relatively insensitive to calibration. We explored two ART scenarios, at increasing coverage : ART initiation based on patients reaching a CD4 cell count threshold, or based on time elapsed since infection (a scenario that mimics the \"universal testing and treatment\" aspirations). We found that HIV virulence is generally unchanged in scenarios of CD4-based initiation. However, with ART initiation based on time since infection, virulence can increase moderately within several years of ART rollout, under high coverage and early treatment initiation, albeit within the context of rapidly shrinking epidemics. Our modeling study suggests that increasing virulence driven by universal test and treat is likely not a major public health concern, but could be monitored in sentinel surveillance, in a manner similar to transmitted drug resistance.

Evolutionary Biology

Craniofacial shape transition across the house mouse hybrid zone: implications for the genetic architecture and evolution of between-species differences

Craniofacial shape differences between taxa have often being linked to environmental adaptation, e.g. to new food sources, or have been studied in the context of domestication. Evidence for the genetic basis of such phenotypic differences to date suggests that within- as well as between-species variation has an oligogenic basis, i.e. few loci of large effect explain most of the variation. In mice, it has been shown that within-population craniofacial variation has a highly polygenic basis, but there are no data regarding the genetic basis of between-species differences. Here, we address this question using a phenotype-focused approach. Using 3D geometric morphometrics, we phenotyped a panel of mice derived from a natural hybrid zone between M. m. domesticus and M. m. musculus, and quantify the transition of craniofacial shape along the hybridization gradient. We find a continuous shape transition along the hybridization gradient, and unaltered developmental stability associated with hybridization. This suggests that the morphospace between the two subspecies is continuous despite reproductive isolation and strong barriers to gene flow. We show that quantitative changes in genome composition generate quantitative changes in craniofacial shape; this supports a highly polygenic basis for between-species craniofacial differences in the house mouse. We discuss our findings in the context of oligogenic versus polygenic models of the genetic architecture of morphological traits.

Evolutionary Biology

The infinitesimal model

Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. We first review the long history of the infinitesimal model in quantitative genetics. Then we provide a definition of the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, ... We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. In each case, by conditioning on the pedigree relating individuals in the population, we incorporate arbitrary selection and population structure. We suppose that we can observe the pedigree up to the present generation, together with all the ancestral traits, and we show, in particular, that the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order [Formula]. Simulations suggest that in particular cases the convergence may be as fast as 1/M.

Evolutionary Biology

A tradeoff between the ecological and evolutionary stabilities of public goods genes in microbial populations

Microbial populations often rely on the cooperative production of extracellular \"public goods\" molecules. The cooperative nature of public good production may lead to minimum viable population sizes, below which populations collapse. In addition, \"cooperator\" public goods producing cells face evolutionary competition from non-producing mutants, or \"freeloaders\". Thus, public goods cooperators have to be stable not only to the invasion of freeloaders, but also to ecological perturbations that may push their numbers too small to be sustainable. Through a combination of experiments with microbial populations and mathematical analysis of the Ecological Public Goods Game, we show that game parameters and experimental conditions that improve the evolutionary stability of cooperators also lead to a low ecological stability of the cooperator population. Complex regulatory strategies mimicking those used by microbes in nature may allow cooperators to beat this eco-evolutionary stability tradeoff and become resistant to freeloaders while at the same time maximizing their ecological stability. Our results thus identify the coupled eco-evolutionary stability as being key for the long-term viability of microbial public goods cooperators.

Evolutionary Biology

Into the tropics: phylogenomics and evolutionary dynamics of a contrarian clade of ants

AimThe standard latitudinal diversity gradient (LDG), in which species richness decreases from equator to pole, is a pervasive pattern observed in most groups of organisms. Despite its commonness, an increasing number of non-conforming lineages have been identified, presenting a challenge for general explanations of the standard LDG. Although problematic, documenting and studying these contrarian groups can help us to better understand LDGs generally. To that end we identify the ant tribe Stenammini, a diverse lineage with over 400 species, as a contrarian clade, and we attempt to explain the groups atypical diversity pattern using a historical approach. We evaluate the following alternative hypotheses: time-for-speciation/center-of-origin (TFS/COO), niche conservatism, and differences in diversification rate.\n\nLocationGlobal.\n\nMethodsWe examine the shape of the LDG in Stenammini by plotting latitudinal midpoints for all extant species. We then infer a robust phylogeny using a phylogenomic approach that employs ultraconserved element loci and we use the phylogeny to estimate divergence dates, biogeographic history, and ancestral habitats. We also test for diversification rate heterogeneity across the tree and among lineages within the tribe.\n\nResultsStenammini has a skewed inverse latitudinal diversity gradient with an extratropical richness peak in the northern temperate zone. Our phylogenomic approach resulted in a robust phylogeny revealing five major clades and several instances of non-monophyly among genera (Goniomma, Aphaenogaster). The tribe and most major lineages originated in the temperate zone and inhabited temperate niches. Crown Stenammini dates to 52 Ma (Eocene Climatic Optimum) and most major lineages appeared soon after during a period of global cooling. Despite its temperate origin, the group invaded the tropics at least six times, but failed to diversify greatly there. Across the tree diversification increased from 17.2-1.9 Ma following the Mid-Miocene Climatic Optimum, and among lineages there was a rate increase in Holarctic Aphaenogaster + Messor just prior to 17.2 Ma.\n\nMain ConclusionsOur results suggest that time, niche conservatism, and increased diversification have all contributed to the inverse latitudinal gradient in Stenammini. Among these processes, niche conservatism may be less important given that the tribe has dispersed to the tropics multiple times.

Evolutionary Biology

Tunable bet hedging in yeast responses to osmotic stress

Microbes limit risk by stochastic bet hedging - low frequency expression of less fit, slow growing cells constitutively preadapted against many stresses including antibiotics. By contrast, here we report continuous variation in the induced frequency of cells with slow osmotic stress signaling, survival and proliferation among 50 ecologically-distinct strains of budding yeast challenged by sudden hyperosmotic stress. Despite extensive variation in early mortality, strains displayed robust perfect adaptation and recovery of steady-state viability in moderate stress. In severe stress survival depended on strain-specific proportions of cells with divergent strategies. Cautious cells survived without dividing; reckless cells attempted to divide too soon and failed, killing both mother and daughter. We show that heritable frequencies of cautious and reckless cells produce a rapidly diversifying template for microbial bet hedging that mimics natural variation in stress responses whose timing, amplitude and frequency could evolve - be tuned by - different patterns of environmental stress.

Evolutionary Biology

High-resolution maps of hunter-gatherer social networks reveal human adaptation for cultural exchange

Are interactions with unrelated and even unknown individuals a by-product of modern life in megacities? Here we argue instead that social ties among non-kin are a crucial human adaptation. By deploying a new portable wireless sensing technology (motes), we mapped social networks in Agta and BaYaka hunter-gatherers in unprecedented detail. We show that strong friendships with non-kin optimize the global efficiency of their social networks thereby facilitating cultural exchange, and that the adaptation for forming friendship ties appears early in development. The ability to extend networks and form strong non-kin ties may explain some human distinctive characteristics such as hypersociality and cumulative culture, and the tendency to exchange ideas with unrelated and unknown individuals in megacities and online social networks.\n\nOne Sentence SummarySocial networks of two hunter-gatherer groups in Congo and the Philippines reveal that friendships are an ancestral adaptation for the exchange of information and culture.

Evolutionary Biology

Conserved gene clusters in the scrambled plastomes of IRLC legumes (Fabaceae: Trifolieae and Fabeae).

The plastid genome retains several features from its cyanobacterial-like ancestor, one being the co-transcriptional organization of genes into operon-like structures. Some plastid operons have been identified but undoubtedly many more remain undiscovered. Here we utilize the highly variable plastome structure that exists within certain legumes of the inverted repeat lost clade (IRLC) to find conserved gene clusters. These plastomes exhibit an unusually high frequency of translocations and inversions. We analysed the plastomes of 23 legume species and identified 32 locally collinear blocks (LCBs), which are regions within the plastid genomes that occur in different orientation and/or order among the plastid genomes but are themselves free from internal rearrangements. Several represent gene clusters that have previously been recognized as plastid operons. It appears that the number of LCBs has reached saturation in our data set, suggesting that these LCBs are not random, but likely represent legume plastid operons protected from internal rearrangement by functional constraint. Some of the LCBs we identify, such as psbD/C/Z, are previously known plastid operons. Others, such as rpl32-ndhF-psbA-matK-rbcL-atpB-atpE, may represent novel polycistronic operons in legumes.

Evolutionary Biology

Micro- and macroevolutionary trade-offs in plant-feeding insects

A long-standing hypothesis asserts that plant-feeding insects specialize on particular host plants because of negative interactions (trade-offs) between adaptations to alternative hosts, yet empirical evidence for such trade-offs is scarce. Most studies have looked for microevolutionary performance trade-offs within insect species, but host-use could also be constrained by macroevolutionary trade-offs caused by epistasis and historical contingency. On the other hand, evolutionary interactions between adaptations to diverse hosts could be neutral or positive rather than negative. Here we used a phylogenetic approach to estimate the micro-and macroevolutionary correlations between use of alternative host plants within two major orders of plant-feeding insects: Lepidoptera (caterpillars) and Hemiptera (true bugs). Across 1604 caterpillar species, we found both positive and negative pairwise correlations between use of diverse host taxa, with overall network patterns suggesting that different host-use constraints act over micro-and macroevolutionary timescales. In contrast, host-use patterns of 955 true bug species revealed uniformly positive correlations between presence on the same host taxa over both timescales. The lack of consistent patterns across timescales and insect orders indicates that host-use trade-offs are historically contingent rather than universal constraints. Moreover, we observed few negative correlations overall despite the wide taxonomic and ecological diversity of the focal host taxa, suggesting that positive interactions between host-use adaptations, not trade-offs, dominate the long-term evolution of host use in plant-feeding insects.

Evolutionary Biology

The molecular chaperone DnaK accelerates protein evolution

Molecular chaperones, also known as heat-shock proteins, refold misfolded proteins and help other proteins reach their native conformation. Thanks to these abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL, can buffer the deleterious phenotypic effects of mutations that alter protein structure and function. Hsp70 chaperones use a chaperoning mechanism different from Hsp90 and GroEL, and it is not known whether they can also buffer mutations. Here, we show that they can. To this end, we performed a mutation accumulation experiment in Escherichia coli, followed by whole-genome resequencing. Our sequence data shows that overexpression of the Hsp70 chaperone DnaK increases the tolerance of its clients for nonsynonymous nucleotide substitutions and nucleotide insertions and deletions. We also show that this elevated mutational buffering on short evolutionary time scales translates into differences in evolutionary rates on intermediate and long evolutionary time scales. To this end, we compared the evolutionary rates of DnaK clients and nonclients using the genomes of E. coli, Salmonella typhimurium, and 83 other gamma-proteobacterial species. We find that clients that interact strongly with DnaK evolve faster than weakly interacting clients. Our results imply that all three major chaperone classes can buffer mutations and affect protein evolution. They illustrate how an individual protein like a chaperone can have a disproportionate effect on proteome evolution.

Evolutionary Biology

Analytical results for directional and quadratic selection gradients for log-linear models of fitness functions

O_LIEstablished methods for inference about selection gradients involve least-squares regression of fitness on phenotype. While these methods are simple and may generally be quite robust, they do not account well for distributions of fitness.\nC_LIO_LISome progress has previously been made in relating inferences about trait-fitness relationships from generalised linear models to selection gradients in the formal quantitative genetic sense. These approaches involve numerical calculation of average derivatives of relative fitness with respect to phenotype.\nC_LIO_LIWe present analytical results expressing selection gradients as functions of the coefficients of generalised linear models for fitness in terms of traits. The analytical results allow calculation of univariate and multivariate directional, quadratic, and correlational selection gradients from log-linear and log-quadratic models.\nC_LIO_LIThe results should be quite generally applicable in selection analysis. They apply to any generalised linear model with a log link function. Furthermore, we show how they apply to some situations including inference of selection from (molecular) paternity data, capture-mark-recapture analysis, and survival analysis. Finally, the results may bridge some gaps between typical approaches in empirical and theoretical studies of natural selection.\nC_LI

Evolutionary Biology

Bayesian Inference of the Evolution of a Phenotype Distribution on a Phylogenetic Tree

The distribution of a phenotype on a phylogenetic tree is often a quantity of interest. Many phenotypes have imperfect heritability, so that a measurement of the phenotype for an individual can be thought of as a single realisation from the phenotype distribution of that individual. If all individuals in a phylogeny had the same phenotype distribution, measured phenotypes would be randomly distributed on the tree leaves. This is however often not the case, implying that the phenotype distribution evolves over time. Here we propose a new model based on this principle of evolving phenotype distribution on the branches of a phylogeny, which is different from ancestral state reconstruction where the phenotype itself is assumed to evolve. We develop an efficient Bayesian inference method to estimate the parameters of our model and to test the evidence for changes in the phenotype distribution. We use multiple simulated datasets to show that our algorithm has good sensitivity and specificity properties. Since our method identifies branches on the tree on which the phenotype distribution has changed, it is able to break down a tree into components for which this distribution is unique and constant. We present two applications of our method, one investigating the association between HIV genetic variation and human leukocyte antigen, and the other studying host range distribution in a lineage of Salmonella enterica, and we discuss many other potential applications. All the methods described in this paper are implemented in a software package called TreeBreaker which is freely available for download at https://github.com/ansariazim/TreeBreaker

Evolutionary Biology

Natural selection driven by DNA binding proteins shapes genome-wide motif statistics

Ectopic DNA binding by transcription factors and other DNA binding proteins can be detrimental to cellular functions and ultimately to organismal fitness. The frequency of protein-DNA binding at non-functional sites depends on the global composition of a genome with respect to all possible short motifs, or k-mer words. To determine whether weak yet ubiquitous protein-DNA interactions could exert significant evolutionary pressures on genomes, we correlate in vitro measurements of binding strengths on all 8-mer words from a large collection of transcription factors, in several different species, against their relative genomic frequencies. Our analysis reveals a clear signal of purifying selection to reduce the large number of weak binding sites genome-wide. This evolutionary process, which we call global selection, has a detectable hallmark in that similar words experience similar evolutionary pressure, a consequence of the biophysics of protein-DNA binding. By analyzing a large collection of genomes, we show that global selection exists in all domains of life, and operates through tiny selective steps, maintaining genomic binding landscapes over long evolutionary timescales.

Evolutionary Biology

Generation of mutation hotspots in ageing bacterial colonies

How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation: most mutations were located in just a few hotspots in the genome and over time, mutations increasingly originated from 8-oxo-guanosine, formed exclusively on the transcribed strand.

Evolutionary Biology

Pollinator specialization imposes stronger evolutionary constraints on flower shape

Flowers show important structural variation as reproductive organs but the evolutionary forces underlying this diversity are still poorly understood. In animal-pollinated species, flower shape is strongly fashioned by selection imposed by pollinators, which is expected to vary according to guilds of effective pollinators. Using the Antillean subtribe Gesneriinae (Gesneriaceae), we tested the hypothesis that pollination specialists pollinated by one functional type of pollinator have maintained more similar corolla shapes through time due to stronger selection constraints compared to species with more generalist pollination strategies. Using geometric morphometrics and evolutionary models, we showed that the corolla of hummingbird specialists, bat specialists, and species with a mixed-pollination strategy (pollinated by hummingbirds and bats; thus a more generalist strategy) have distinct shapes and that these shapes have evolved under evolutionary constraints. However, we did not find support for smaller disparity in corolla shape for hummingbird specialists compared to more generalist species. This could be because the corolla shape of more generalist species in subtribe Gesneriinae, which has evolved multiple times, is finely adapted to be effectively pollinated by both bats and hummingbirds. These results suggest that pollination generalization is not necessarily associated with relaxed selection constraints.

Evolutionary Biology

Species Identification by Bayesian Fingerprinting: A Powerful Alternative to DNA Barcoding

A number of methods have been developed to use genetic sequence data to identify and delineate species. Some methods are based on heuristics, such as DNA barcoding which is based on a sequence-distance threshold, while others use Bayesian model comparison under the multispecies coalescent model. Here we use mathematical analysis and computer simulation to demonstrate large differences in statistical performance of species identification between DNA barcoding and Bayesian inference under the multispecies coalescent model as implemented in the BPP program. We show that a fixed genetic-distance threshold as used in DNA barcoding is problematic for delimiting species, even if the threshold is \"optimized\", because different species have different population sizes and different divergence times, and therefore display different amounts of intra-species versus inter-species variation. In contrast, BPP can reliably delimit species in such situations with only one locus and rarely supports a wrong assignment with high posterior probability. While under-sampling or rare specimens may pose problems for heuristic methods, BPP can delimit species with high power when multi-locus data are used, even if the species is represented by a single specimen. Finally we demonstrate that BPP may be powerful for delimiting cryptic species using specimens that are misidentified as a single species in the barcoding library.

Evolutionary Biology

Sporulation, bacterial cell envelopes, and the origin of life

Four recent papers from our group exploiting the power of electron cryotomography to produce 3-D reconstructions of intact cells in a near-native state have led to the proposal that an ancient sporulation-like event gave rise to the second membrane in diderm bacteria. Here we review the images of sporulating monoderm and diderm cells which show how sporulation leads to diderm cells. We also review the images of Gram-negative and Gram-positive cell walls that show they are more closely related than previously thought, and explain how this provides critical support for the hypothesis. Mapping the distribution of cell envelope architectures onto the most recent phylogenetic tree of life then leads to the conclusion that the diderm cell plan, and therefore the sporulation-like event that gave rise to it, must be very ancient. One explanation for the biogeologic record is that during the cataclysmic transitions of early Earth, cellular evolution may have gone through a bottleneck where only spores survived (LUCA was a spore).

Evolutionary Biology

Trait Heritability in Major Transitions

A crucial component of major transitions theory is that after the transition, adaptation occurs primarily at the level of the new, higher-level unit. For collective-level adaptations to occur, though, collective-level traits must be heritable. Since collective-level trait values are functions of lower-level trait values, collective-level heritability is related to particle-level heritability. However, the nature of this relationship has rarely been explored in the context of major transitions. We examine relationships between particle-level heritability and collective-level heritability for several functions that express collective-level trait value in terms of particle-level trait values. When a collective-level trait value is a linear function of particle-level trait values, the heritability of a collective-level trait is never less than that of the corresponding particle-level trait and is higher under most conditions. For more complicated functions, collective-level heritability is higher under most conditions, but can be lower when the function relating particle to cell-level trait values is sensitive to small fluctuations in the state of the particles within the collective. Rather than being an impediment to major transitions, we show that collective-level heritability superior to that of the lower-level units can often arise for free, simply as a byproduct of collective formation.

Evolutionary Biology