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The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern 1 – 4 . Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2. Results indicate that the sublineages BA.4 and BA.5 of SARS-CoV-2 Omicron variants have similar pathogenicity to that of the BA.2 sublineage in rodents, highlighting the importance of evaluating viral replication and pathogenesis using clinical isolates.

Population-level spacer diversity is a key fitness determinant of CRISPR-Cas adaptive immune systems because it limits the emergence of escape virus. Diversity in CRISPR-Cas immunity The CRISPR-Cas adaptive immune system of prokaryotes uses spacer sequences derived from viruses and other invading mobile genetic elements to target and destroy these elements in a sequence-specific manner. As a result, spacer diversity is often high in bacterial populations, but its importance has been unclear as it has been proposed that viruses overcome spacer diversity by evolving escape mutations. Using experimental evolution to track the co-evolution of a Pseudomonas aeruginosa bacteriophage with its host bacterium, Edze Westra and colleagues demonstrate that a high level of spacer diversity actually drives the virus population to extinction, as a result of the synergy between spacer diversity and the high specificity of viral infection. These data reveal that high spacer diversity is key to the success of CRISPR-Cas immunity as it limits the ability of viruses to escape. Prokaryotic CRISPR-Cas adaptive immune systems insert spacers derived from viruses and other parasitic DNA elements into CRISPR loci to provide sequence-specific immunity 1 , 2 . This frequently results in high within-population spacer diversity 3 , 4 , 5 , 6 , but it is unclear if and why this is important. Here we show that, as a result of this spacer diversity, viruses can no longer evolve to overcome CRISPR-Cas by point mutation, which results in rapid virus extinction. This effect arises from synergy between spacer diversity and the high specificity of infection, which greatly increases overall population resistance. We propose that the resulting short-lived nature of CRISPR-dependent bacteria–virus coevolution has provided strong selection for the evolution of sophisticated virus-encoded anti-CRISPR mechanisms 7 .

Steady-state protein abundance is set by four rates: transcription, translation, mRNA decay and protein decay. A given protein abundance can be obtained from infinitely many combinations of these rates. This raises the question of whether the natural rates for each gene result from historical accidents, or are there rules that give certain combinations a selective advantage? We address this question using high-throughput measurements in rapidly growing cells from diverse organisms to find that about half of the rate combinations do not exist: genes that combine high transcription with low translation are strongly depleted. This depletion is due to a trade-off between precision and economy: high transcription decreases stochastic fluctuations but increases transcription costs. Our theory quantitatively explains which rate combinations are missing, and predicts the curvature of the fitness function for each gene. It may guide the design of gene circuits with desired expression levels and noise. The same protein abundance can be achieved by many combinations of transcription, translation and degradation rates. Here, the authors find that genes combining high transcription with low translation rate are rare due to a trade-off between the cost of transcription and expression noise.

Populations of the flour beetle Tribolium castaneum with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. Mutational load minimized by sexual selection Sexual reproduction is more costly than the asexual kind because the genetic contribution of a given individual to the next generation is halved. A disadvantage of asexual reproduction is the accumulation of mutations, and it has been suggested that sexual selection, which acts when reproduction is achieved through competition and choice, might purge mutation. Matthew Gage and colleagues tested this theory in a study of populations of the flour beetle Tribolium castaneum raised for seven years under conditions of strong or weak sexual selection. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness, even with strong inbreeding, with some families continuing to survive after 20 generations of sibling–sibling mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after the tenth generation. Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring 1 . It has been theorized that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load 2 , 3 , 4 . Under sexual selection, competition between (usually) males and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which is contingent to mutation load, then sexually selected filtering through ‘genic capture’ 5 could offset the costs of sex because it provides genetic benefits to populations. Here we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for 6 to 7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress.

Hypervirulent K . pneumoniae (hvKp) is a distinct pathotype that causes invasive community-acquired infections in healthy individuals. Hypermucoviscosity (hmv) is a major phenotype associated with hvKp characterized by copious capsule production and poor sedimentation. Dissecting the individual functions of CPS production and hmv in hvKp has been hindered by the conflation of these two properties. Although hmv requires capsular polysaccharide (CPS) biosynthesis, other cellular factors may also be required and some fitness phenotypes ascribed to CPS may be distinctly attributed to hmv. To address this challenge, we systematically identified genes that impact capsule and hmv. We generated a condensed, ordered transposon library in hypervirulent strain KPPR1, then evaluated the CPS production and hmv phenotypes of the 3,733 transposon mutants, representing 72% of all open reading frames in the genome. We employed forward and reverse genetic screens to evaluate effects of novel and known genes on CPS biosynthesis and hmv. These screens expand our understanding of core genes that coordinate CPS biosynthesis and hmv, as well as identify central metabolism genes that distinctly impact CPS biosynthesis or hmv, specifically those related to purine metabolism, pyruvate metabolism and the TCA cycle. Six representative mutants, with varying effect on CPS biosynthesis and hmv, were evaluated for their impact on CPS thickness, serum resistance, host cell association, and fitness in a murine model of disseminating pneumonia. Altogether, these data demonstrate that hmv requires both CPS biosynthesis and other cellular factors, and that hmv and CPS may serve distinct functions during pathogenesis. The integration of hmv and CPS to the metabolic status of the cell suggests that hvKp may require certain nutrients to specifically cause deep tissue infections.

Assays to accurately estimate relative fitness of bacteria growing in multistrain communities can advance our understanding of how selection shapes diversity within a lineage. Here, we present a variant of the “evolve and resequence” approach both to estimate relative fitness and to identify genetic variants responsible for fitness variation of symbiotic bacteria in free-living and host environments. We demonstrate the utility of this approach by characterizing selection by two plant hosts and in two free-living environments (sterilized soil and liquid media) acting on synthetic communities of the facultatively symbiotic bacterium Ensifer meliloti. We find (i) selection that hosts exert on rhizobial communities depends on competition among strains, (ii) selection is stronger inside hosts than in either free-living environment, and (iii) a positive host-dependent relationship between relative strain fitness in multistrain communities and host benefits provided by strains in single-strain experiments. The greatest changes in allele frequencies in response to plant hosts are in genes associated with motility, regulation of nitrogen fixation, and host/rhizobia signaling. The approach we present provides a powerful complement to experimental evolution and forward genetic screens for characterizing selection in bacterial populations, identifying gene function, and surveying the functional importance of naturally occurring genomic variation.

Sexual selection has manifold ecological and evolutionary consequences, making its net effect on population fitness difficult to predict. A powerful empirical test is to experimentally manipulate sexual selection and then determine how population fitness evolves. Here, we synthesise 459 effect sizes from 65 experimental evolution studies using meta-analysis. We find that sexual selection on males tends to elevate the mean and reduce the variance for many fitness traits, especially in females and in populations evolving under stressful conditions. Sexual selection had weaker effects on direct measures of population fitness such as extinction rate and proportion of viable offspring, relative to traits that are less closely linked to population fitness. Overall, we conclude that the beneficial population-level consequences of sexual selection typically outweigh the harmful ones and that the effects of sexual selection can differ between sexes and environments. We discuss the implications of these results for conservation and evolutionary biology. Sexual selection has the potential to either increase or decrease absolute fitness. Here, Cally et al. perform a meta-analysis of 65 experimental evolution studies and find that sexual selection on males tends to increase fitness, especially in females evolving under stressful conditions.

Manipulation of the frequency of naturally occurring colour patterns within replicate pools of fish at three sites shows that males with rare colour patterns have higher reproductive fitness, demonstrating negative frequency-dependent selection mediated by sexual selection. Reasons to be different Given that natural selection is both ubiquitous and remorseless, how is it that variation is maintained in populations? This pressing question in evolutionary biology is answered by Kimberly Hughes and colleagues in a study of guppies ( Poecilia reticulata ), a particularly useful model system because guppy male colouration is one of the most genetically variable organismal traits known. It was shown previously that in a population of brightly coloured guppies, males with rare colour patterns tend to thrive, against expectation. Hughes et al . show, using carefully controlled wild populations, not only that female guppies prefer to mate with these rare males, but that the males produce more offspring than those of more common stripe. This phenomenon, known as negative frequency-dependent selection, shows that there is a price on exclusivity and provides a mechanism for maintaining variation in a population. To understand the processes that maintain genetic diversity is a long-standing challenge in evolutionary biology, with implications for predicting disease resistance, response to environmental change, and population persistence 1 , 2 , 3 . Simple population genetic models are not sufficient to explain the high levels of genetic diversity sometimes observed in ecologically important traits 2 . In guppies ( Poecilia reticulata ), male colour pattern is both diverse and heritable, and is arguably one of the most extreme examples of morphological polymorphism known 4 , 5 . Negative frequency-dependent selection (NFDS), a form of selection in which genotypes are favoured when they are rare 6 , can potentially maintain such extensive polymorphism, but few experimental studies have confirmed its operation in nature 7 , 8 . Here we use highly replicated experimental manipulations of natural populations to show that males with rare colour patterns have higher reproductive fitness, demonstrating NFDS mediated by sexual selection. Rare males acquired more mates and sired more offspring compared to common males and, as previously reported, had higher rates of survival 8 . Orange colour, implicated in other studies of sexual selection in guppies, did predict male reproductive success, but only in one of three populations. These data support the hypothesis that NFDS maintains diversity in the colour patterns of male guppies through two selective agents, mates and predators. Similar field-based manipulations of genotype frequencies could provide a powerful approach to reveal the underlying ecological and behavioural mechanisms that maintain genetic and phenotypic diversity.

The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage. A computational approach for predicting the future evolution of the human influenza virus, based on population-genetic data of previous strains, is presented; this model holds promise for improving vaccine strain selection for seasonal influenza. Keeping tabs on influenza virus evolution Marta Łuksza and Michael Lässig present a computational approach for predicting the future evolution of influenza virus. The authors develop a fitness model for the influenza haemagglutinin protein, based on population-genetic data from all previous strains, that allows them to predict the future evolution of currently existing clades. This computational model holds promise for improving vaccine strain selection.

If climate change outpaces the rate of adaptive evolution within a site, populations previously well adapted to local conditions may decline or disappear, and banked seeds from those populations will be unsuitable for restoring them. However, if such adaptational lag has occurred, immigrants from historically warmer climates will outperform natives and may provide genetic potential for evolutionary rescue. We tested for lagging adaptation to warming climate using banked seeds of the annual weed Arabidopsis thaliana in common garden experiments in four sites across the species’ native European range: Valencia, Spain; Norwich, United Kingdom; Halle, Germany; and Oulu, Finland. Genotypes originating from geographic regions near the planting site had high relative fitness in each site, direct evidence for broad-scale geographic adaptation in this model species. However, genotypes originating in sites historically warmer than the planting site had higher average relative fitness than local genotypes in every site, especially at the northern range limit in Finland. This result suggests that local adaptive optima have shifted rapidly with recent warming across the species’ native range. Climatic optima also differed among seasonal germination cohorts within the Norwich site, suggesting that populations occurring where summer germination is common may have greater evolutionary potential to persist under future warming. If adaptational lag has occurred over just a few decades in banked seeds of an annual species, it may be an important consideration for managing longer-lived species, as well as for attempts to conserve threatened populations through ex situ preservation.