SEARCH · PubMed Health

Results for “evolutionary dynamics”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed2003

The population genetics of sporophytic self-incompatibility in Senecio squalidus L. (Asteraceae): avoidance of mating constraints imposed by low S-allele number.

Senecio squalidus L. (Asteraceae) has been the subject of several ecological and population genetic studies due to its well-documented history of introduction, establishment and spread throughout Britain in the past 300 years. Our recent studies have focused on identifying and quantifying factors associated with the sporophytic self-incompatibility (SSI) system of S. squalidus that may have contributed to its success as a colonist. These findings are of general biological interest because they provide important insights into the short-term evolutionary dynamics of a plant mating system. The number of S-alleles in populations and their dominance interactions were investigated in eight wild British populations using cross-diallel studies. The numbers of S-alleles in British S. squalidus populations are typically low (average of 5.3 S-alleles) and the entire British population is estimated to possess no more than 7-11 S-alleles. Such low numbers of S-alleles are most probably a consequence of population bottlenecks associated with introduction and colonization. Potential evolutionary impacts on SSI caused by a paucity of S-alleles, such as restricted mate availability, are discussed, and we suggest that increased dominance interactions between S-alleles may be an important short-term means of increasing mate availability when S-allele numbers are low.

Alleles↗

PubMed1997

Phylogenetic analysis of a retrotransposon with implications for strong evolutionary constraints on reverse transcriptase.

This study examines the evolutionary dynamics of a retrotransposon in a group of parasitoid wasps. A region containing the reverse transcriptase (RT) domain was sequenced for 43 elements from the genomes of nine different wasp species. Phylogenetic analysis of the elements revealed concordance with taxonomic classification of the host species, and the pattern was consistent with that expected for vertical transmission of a multicopy element during differentiation of the species. Twenty-three of the 43 elements had comparable intact open reading frames in the amplified region, and these were used in an analysis of evolutionary constraint on the amino acid sequence. As previously documented for retroelements, closely related elements exhibited nearly equal substitution rates at nonsynonymous and synonymous sites, but relative nonsynonymous substitution rates decreased as increasingly divergent elements were compared. A statistical test indicated that the decrease was not due to saturation of weakly selected sites. The pattern is most likely caused by a "pseudogene effect." Individual elements are not subject to purifying selection, and therefore, synonymous and nonsynonymous substitutions accumulate at equal rates. Comparisons among closely related elements are influenced strongly by this pseudogene evolution, whereas comparisons among distantly related elements reveal selection on the actively replicating lineages connecting the elements. These distant comparisons more accurately reflect the constraints on the amino acid sequence, and the comparisons among elements in this study indicated strong constraints on RT.

Amino Acid Sequence↗

PubMed1998

Instability of signaling resolution models of parent-offspring conflict.

Recent signaling resolution models of parent-offspring conflict have provided an important framework for theoretical and empirical studies of communication and parental care. According to these models, signaling of need is stabilized by its cost. However, our computer simulations of the evolutionary dynamics of chick begging and parental investment show that in Godfray's model the signaling equilibrium is evolutionarily unstable: populations that start at the signaling equilibrium quickly depart from it. Furthermore, the signaling and nonsignaling equilibria are linked by a continuum of equilibria where chicks above a certain condition do not signal and we show that, contrary to intuition, fitness increases monotonically as the proportion of young that signal decreases. This result forces us to reconsider much of the current literature on signaling of need and highlights the need to investigate the evolutionary stability of signaling equilibria based on the handicap principle.

Animals↗

PubMed2025

Distinct evolutionary trajectories of subgenomic centromeres in polyploid wheat.

BACKGROUND: Centromeres are crucial for precise chromosome segregation and maintaining genome stability during cell division. However, their evolutionary dynamics, particularly in polyploid organisms with complex genomic architectures, remain largely enigmatic. Allopolyploid wheat, with its well-defined hierarchical ploidy series and recent polyploidization history, serves as an excellent model to explore centromere evolution. RESULTS: In this study, we perform a systematic comparative analysis of centromeres in common wheat and its corresponding ancestral species, utilizing the latest comprehensive reference genome assembly available. Our findings reveal that wheat centromeres predominantly consist of five types of centromeric-specific retrotransposon elements (CRWs), with CRW1 and CRW2 being the most prevalent. We identify distinct evolutionary trajectories in the functional centromeres of each subgenome, characterized by variations in copy number, insertion age, and CRW composition. By utilizing CENH3-ChIP data across various ploidy levels, we uncover a series of CRW invasion events that have shaped the evolution of AA subgenome centromeres. Conversely, the evolutionary process of the DD subgenome centromeres involves their expansion from diploid to hexaploid wheat, facilitating adaptation to a larger genomic context. Integration of complete einkorn centromere assemblies and Aegilops tauschii pan-genomes further revealed subgenome-specific centromere evolutionary trajectories. By inclusion of synthetic hexaploid from S2-S3 generations, alongside 2x/6 × natural accessions, we demonstrate that DD subgenome centromere expansion represents a gradual evolutionary process rather than an immediate response to polyploidization. CONCLUSIONS: Our study provides a comprehensive landscape of centromere adaptation, evolution, and maturation, along with insights into how retrotransposon invasions drive centromere evolution in polyploid wheat.

Centromere↗

PubMed1997

A phylogenetic perspective on P transposable element evolution in Drosophila.

The P element, originally described in Drosophila melanogaster, is one of the best-studied eukaryotic transposable elements. In an attempt to understand the evolutionary dynamics of the P element family, an extensive phylogenetic analysis of 239 partial P element sequences has been completed. These sequences were obtained from 40 species in the Drosophila subgenus Sophophora. The phylogeny of the P element family is examined in the context of a phylogeny of the species in which these elements are found. An interesting feature of many of the species examined is the coexistence in the same genome of P sequences belonging to two or more divergent subfamilies. In general, P elements in Drosophila have been transmitted vertically from generation to generation over evolutionary time. However, four unequivocal cases of horizontal transfer, in which the element was transferred between species, have been identified. In addition, the P element phylogeny is best explained in numerous instances by horizontal transfer at various times in the past. These observations suggest that, as with some other transposable elements, horizontal transfer may play an important role in the maintenance of P elements in natural populations.

Animals↗

PubMed2000

Lineage-specific evolutionary rate in mammalian mtDNA.

The existence of a lineage-specific nucleotide substitution rate in mammalian mtDNA has been investigated by analyzing the mtDNA of all available species, that is, 35 complete mitochondrial genomes from 14 mammalian orders. A detailed study of their evolutionary dynamics has been carried out on both ribosomal RNA and first and second codon positions (P12) of H-strand protein-coding genes by using two different types of relative-rate tests. Results are quite congruent between ribosomal and P12 sites. Significant rate variations have been observed among orders and among species of the same order. However, rate variation does not exceed 1.8-fold between the fastest (Proboscidea and Primates) and the slowest (Perissodactyla) evolving orders. Thus, the observed mitochondrial rate variations among taxa do not invalidate the suitability of mtDNA for drawing mammalian phylogeny. Dependence of evolutionary rate differences on variations in mutation and/or fixation rates was examined. Body size, generation time, and metabolic rate were tested, and no significant correlation was observed between them and the taxon-specific evolutionary rates, most likely because the latter might be influenced by multiple overlapping variable constraints.

Animals↗

PubMed2026

Population-level genomic surveillance of human norovirus using wastewater-based whole-genome sequencing.

Wastewater-based surveillance has garnered increasing attention as a valuable approach for capturing community-level infection dynamics that are often difficult to detect through clinical reporting systems alone. In this study, we analyzed human norovirus genotype distributions and whole-genome-level variations in wastewater samples collected in Gwangju, Korea. These results were interpreted in conjunction with a documented foodborne outbreak to evaluate the epidemiological relevance of wastewater-based monitoring. Human norovirus concentrations were quantified using TaqMan Array Card-based RT-qPCR, and whole-genome next-generation sequencing (NGS) was performed to obtain viral read counts and reads per kilobase per million filtered reads values. Overall, strong correlations were observed between RT-qPCR-based concentrations and NGS-derived metrics. Genotype dynamics varied among wastewater treatment plants, reflecting differences in catchment size and local population characteristics. In particular, the relative abundance of GII.17[P17] increased during epidemiological week 50, temporally coinciding with a documented local foodborne outbreak. Variant analysis revealed that wastewater samples exhibited mixed nucleotide patterns, with multiple alleles coexisting at varying relative frequencies rather than fixed substitutions. Notably, some nonsynonymous variants detected in clinical samples were also observed in wastewater samples collected surrounding the outbreak period. Together, these findings demonstrate that wastewater-based whole-genome surveillance can capture both genotype-level shifts and nucleotide-level dynamics at the population scale, highlighting its potential as a complementary tool for monitoring community-level norovirus circulation and outbreak-associated genotype dynamics.IMPORTANCEWastewater-based surveillance is increasingly recognized as a promising approach for capturing community-level infection dynamics that are often missed by clinical surveillance. In this study, we applied whole-genome sequencing to wastewater samples collected in Gwangju, South Korea, to comprehensively characterize human norovirus genotype distributions and genetic variation. Distinct genotype patterns were observed across wastewater treatment plants, reflecting differences in catchment population size and local characteristics. Notably, an increase in the GII.17[P17] genotype detected in wastewater coincided with a foodborne outbreak investigated in Gwangju, demonstrating the potential of wastewater surveillance to reflect ongoing community transmission and emerging outbreak-associated genotypes. In addition, wastewater samples contained diverse and coexisting genetic variants, capturing population-level viral diversity and evolutionary dynamics that are not readily detected through clinical surveillance alone. These findings highlight the value of wastewater-based whole-genome surveillance for monitoring community-level viral circulation and support its integration as a complementary strategy to existing clinical surveillance systems.

genotype dynamics↗

PubMed1996

Disequilibrium mapping: composite likelihood for pairwise disequilibrium.

The pattern of linkage disequilibrium between a disease locus and a set of marker loci has been shown to be a useful tool for geneticists searching for disease genes. Several methods have been advanced to utilize the pairwise disequilibrium between the disease locus and each of a set of marker loci. However, none of the methods take into account the information from all pairs simultaneously while also modeling the variability in the disequilibrium values due to the evolutionary dynamics of the population. We propose a Composite Likelihood (CL) model that has these features when the physical distances between the marker loci are known or can be approximated. In this instance, and assuming that there is a single disease mutation, the CL model depends on only three parameters, the recombination fraction between the disease locus and an arbitrary marker locus, theta, the age of the mutation, and a variance parameter. When the CL is maximized over a grid of theta, it provides a graph that can direct the search for the disease locus. We also show how the CL model can be generalized to account for multiple disease mutations. Evolutionary simulations demonstrate the power of the analyses, as well as their potential weaknesses. Finally, we analyze the data from two mapped diseases, cystic fibrosis and diastrophic dysplasia, finding that the CL method performs well in both cases.

Computer Simulation↗

PubMed1995

Immune responses against multiple epitopes.

The current understanding of antigenic escape dynamics is based on models with single epitopes. The usual idea is that a mutation which enables a pathogen (virus, bacteria, etc) to escape from a given immune response confers a selective advantage. The "escape mutant" may then increase in abundance until it induces a new specific response against itself. In this paper a new picture is developed, based on mathematical models of immune responses against several epitopes; the simplest such models can have very complicated dynamics, with some surprising features. The emergence of an escape mutant can shift the immunodominant response to another epitope. Even in the absence of mutations, antigenic oscillation is found, with distinct peaks of different virus variants and fluctuations in the size and specificity of the immune responses. The model also provides a general theory for immunodominance in the presence of antigenic variation. Immunodominance is determined by the immunogenicity and by the antigenic diversity of the competing epitopes. Antigenic oscillations and fluctuations in the cytotoxic T-lymphocyte response have been observed in infections with the human immunodeficiency virus (HIV). Shifting the immune responses to weaker epitopes can represent a mechanism for disease progression based on evolutionary dynamics and antigenic diversity of the virus.

Antigenic Variation↗

PubMed1999

Evolution of the genetic covariance between male and female components of mate recognition: an experimental test.

The evolution of a positive genetic correlation between male and female components of mate recognition systems will result as a consequence of assortative mating and, in particular, is central to a number of theories of sexual selection. Although the existence of such genetic correlations has been investigated in a number of taxa, it has yet to be shown that such correlations evolve and whether they may evolve as rapidly as suggested by sexual selection models. In this study, I used a hybridization experiment to disrupt natural mate recognition systems and then observed the subsequent evolutionary dynamics of the genetic correlation between male and female components for 56 generations in hybrids between Drosophila serrata and Drosophila birchii. The genetic correlation between male and female components evolved from 0.388 at generation 5 to 1.017 at generation 37 and then declined to -0.040 after a further 19 generations. These results indicated that the genetic basis of the mate recognition system in the hybrid populations evolved rapidly. The initial rapid increase in the genetic correlation was consistent with the classic assumption that male and female components will coevolve under sexual selection. The subsequent decline in genetic correlation may be attributable to the fixation of major genes, or, alternatively, may be a result of a cyclic evolutionary change in mate recognition.

Animals↗

PubMed2026

Genome-wide identification and functional analysis of the BES1-like (VfBES1) gene family in Vernicia fordii reveals its role in floral development.

BACKGROUND: Vernicia fordii Hemsl (also known as Tung tree), an significant commercial oil-producing tree species, is a monoecious and diclinous species with male and female flowers on the same inflorescence; however, the molecular mechanisms governing its floral sex determination remain elusive, particularly the genetic basis underlying the skewed female-to-male flower ratio and the evolutionary dynamics of sex-related gene families, which severely restrict targeted breeding for yield enhancement. In the model plant Arabidopsis, the BRI1 EMS SUPPRESSOR 1 (BES1) transcription factor family plays a crucial role in Brassinosteroid (BR) signaling and reproductive development. However, its function remains largely unexplored in woody perennials. RESULTS: In this study, we introduce the genome-wide identification and functional characterization of the BES1-like (VfBES1) gene family in the Tung tree for the first time. Integrative multi-omics approaches reveal seven VfBES1 genes that are clustered into three phylogenetically distinct clades, each characterized by clade-specific motifs and structural simplicity. Segmental duplication events (VfBES1-1/VfBES1-5 and VfBES1-4/VfBES1-7) and promoter cis-element enrichment (hormone-responsive and abiotic stress-related motifs) highlight evolutionary innovation and functional diversification. Spatiotemporal expression profiling reveals VfBES1 genes' tissue- and stage-specific roles. VfBES1-1 predominantly expresses in female flowers and fruits, suggesting its possible roles in late-stage sex maintenance or ovule and fruit development. VfBES1-2 and VfBES1-6 exhibit male flower-specific and early floral developmental activation, respectively. Nuclear-localized VfBES1-6 displays co-expression with VfMYB35-1 gene, which is a regulator of male structure degeneration. CONCLUSIONS: Findings in this study shed light on the regulatory roles of VfBES1 genes in the floral development of the Tung tree, providing a reference for its precision breeding to enhance flowering synchrony and seed productivity. This study also provides a comparative framework for understanding the functional diversity of BES1-like genes in non-model woody plants.

Flowers↗

PubMed2003

Patterns of nucleotide variation in homoeologous regulatory genes in the allotetraploid Hawaiian silversword alliance (Asteraceae).

Genome-wide duplication (polyploidization) is prevalent in a large number of eukaryotic organisms and is particularly widespread in flowering plants. Polyploid species appear to vary from their diploid progenitors in a variety of ecologically important traits, suggesting that genome duplications provide a mechanism for ecological diversification. Studies of nucleotide variation at duplicate genes that arise via polyploidization allow us to infer the evolutionary forces that act on these polyploid loci. In an effort to examine the evolutionary dynamics of homoeologous loci, molecular population genetic analyses were undertaken for duplicate regulatory genes in the allopolyploid Hawaiian silversword alliance, a premier example of adaptive radiation. The levels and patterns of nucleotide variation for the floral homeotic genes ASAPETALA1 (ASAP1) and ASAPETALA3/TM6 (ASAP3/TM6) were studied in two species representing different lineages within the Hawaiian silversword alliance: Argyroxiphium sandwicense ssp. macrocephalum and Dubautia ciliolata ssp. glutinosa. Homoeologueous copies of ASAP1 and ASAP3/TM6 show differing levels and patterns of nucleotide polymorphism. Duplicate ASAP1 copies have similar levels of nucleotide diversity and haplotype structure in both species; by contrast, duplicate ASAP3/TM6 genes display different levels and patterns of variation in D. ciliolata ssp. glutinosa. Additionally, D. ciliolata ssp. glutinosa appears to be segregating for a moderate frequency null allele in one ASAP3/TM6 homoeologue. These results suggest that differing evolutionary forces can affect duplicate loci arising from allopolyploidization.

Asteraceae↗

PubMed2001

Role of genomic typing in taxonomy, evolutionary genetics, and microbial epidemiology.

Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for discrimination between genotypes. Apart from being an essential component of these fundamental sciences, microbial typing clearly affects several areas of applied microbiological research. The epidemiological investigation of outbreaks of infectious diseases and the measurement of genetic diversity in relation to relevant biological properties such as pathogenicity, drug resistance, and biodegradation capacities are obvious examples. The diversity among nucleic acid molecules provides the basic information for all fields described above. However, researchers in various disciplines tend to use different vocabularies, a wide variety of different experimental methods to monitor genetic variation, and sometimes widely differing modes of data processing and interpretation. The aim of the present review is to summarize the technological and fundamental concepts used in microbial taxonomy, evolutionary genetics, and epidemiology. Information on the nomenclature used in the different fields of research is provided, descriptions of the diverse genetic typing procedures are presented, and examples of both conceptual and technological research developments for Escherichia coli are included. Recommendations for unification of the different fields through standardization of laboratory techniques are made.

Bacteria↗

PubMed2026

Plasmids as persistent genetic reservoirs of bacterial defense systems in wastewater treatment.

BACKGROUND: Bacterial antiphage defense systems play essential roles in microbial ecology, yet their dynamics within urban wastewater systems (UWS) remain poorly characterized. RESULTS: In this study, we performed comprehensive metagenomic and plasmidome analyses on 78 wastewater samples collected during two seasons and four sampling points across UWS from three European countries. We observed a significant reduction in the abundance, diversity, and mobility potential of defense systems during biological treatment. However, these reductions were not directly correlated with changes in microbial abundance. Defense systems were significantly enriched on plasmids, particularly conjugative plasmids, where their gene density was approximately twice as high as on chromosomes and remained relatively stable across compartments. In contrast to chromosomal defense systems, plasmid-borne systems exhibited more frequent co-localization with a wide range of mobile genetic elements (MGEs)-associated genes, thereby facilitating multilayered dissemination networks. Furthermore, we detected a strong correlation between phage abundance and host defense system profiles, indicating ongoing phage-host co-evolutionary dynamics in these environments. CONCLUSIONS: In summary, our results demonstrate that UWS reduce the abundance and diversity of bacterial defense system genes. However, plasmid-associated defense systems can persist through shared mobile genetic reservoirs. These findings underscore the critical role of plasmids in bacterial immunity and provide new insights into defense system dynamics within urban wastewater environments.

Plasmids↗

PubMedDate not supplied

[The population genetics of nodule bacteria].

The data are reviewed on the population structure and evolutionary dynamics of the nodule bacteria (rhizobia) which are among the most intensively studied microorganisms. High level of the population polymorphism was demonstrated for the rhizobia populations using the enzyme electrophoresis (MLEE profiles). The average value of Nei's coefficient of heterogeneity (H = 1 - sigma pi2 [n/(n - 1)]) were: 0.590 for rhizobia (Rhizobium, Bradyrhizobium), 0.368 for enterobacteria (Escherichia, Salmonella, Shigella) and 0.452 for pathogenic bacteria (Bordetella, Borrelia, Erysipelothrix, Haemophilus, Helicobacter, Listeria, Mycobacterium, Neisseria, Staphylococcus) populations. In spite of being devoid of the effective systems for the gene conjugative transfer, many rhizobia populations possess an essentially panmictic structure. However, the enterobacteria populations in which the gene transfer may be facilitated due to the conjugative F- and R-factors, usually display the clonal population structure. The legume host plant is proved to be a key factor that determines the high levels of polymorphism and of panmixis as well as high evolutionary rates of the symbiotic bacteria populations. The host may ensure: a) an increase in mutation and gene transfer frequencies; b) stimulation of the competitive (selective) processes in both symbiotic and free-living rhizobia populations. A "cyclic" model of the rhizobia microevolution is presented which allows to assess the inputs the interstrain competition for the saprophytic growth and for the host nodulation into evolution of a plant-associated rhizobia population. The nodulation competitiveness in the rhizobia populations is responsible for the frequency-dependent selection of the rare genotypes which may arise in the soil bacterial communities as a result of the transfer of symbiotic (sym) genes from virulent rhizobia strains to either avirulent rhizobia or to the other (saprophytic, phytopathogenic) bacteria. Therefore, the nodulation competitiveness may ensure: a) panmictic structure of the natural rhizobia populations; b) high taxonomic diversity of rhizobia which was apparently caused by a broad sym gene expansion in the soil bacterial communities. The kin selection models are presented which explain evolution of the "altruistic" (essential for the host plant, but not for the bacteria themselves) symbiotic traits (e.g., the ability for symbiotic nitrogen fixation and for differentiation into non-viable bacteroids) in the rhizobia populations. These models are based on preferential multiplication of the nitrogen-fixing clones either in planta (due to an elevated supply of the nitrogen-fixing nodules with photosynthates) or ex planta (due to a release of the rhizopines from the nitrogen-fixing nodules). Speaking generally, interactions with the host plants provide a range of mechanisms increasing a genetic heterogeneity and an evolutionary potential in the associated rhizobia populations.

Altruism↗

PubMed2003

Dynamics and genealogy of strains in spatially extended host-pathogen models.

We examine the dynamics of evolution in a generic spatial model of a pathogen infecting a population of hosts, or an analogous predator-prey system. Previous studies of this model have found a range of interesting phenomena that differ from the well-mixed version. We extend these studies by examining the spatial and temporal dynamics of strains using genealogical tracing. When transmissibility can evolve by mutation, strains of intermediate transmissibility dominate even though high-transmissibility mutants have a short-term reproductive advantage. Mutant strains continually arise and grow rapidly for many generations but eventually go extinct before dominating the system. We find that, after a number of generations, the mutant pathogen characteristics strongly impact the spatial distribution of their local host environment, even when there are diverse types coexisting. Extinction is due to the depletion of susceptibles in the local environment of these mutant strains. Studies of spatial and genealogical relatedness reveal the self-organized spatial clustering of strains that enables their impact on the local environment. Thus, we find that selection acts against the high-transmissibility strains on long time-scales as a result of the feedback due to environmental change. Our study shows that averages over space or time should not be assumed to adequately describe the evolutionary dynamics of spatially distributed host-pathogen systems.

Animals↗

PubMed2002

Evolving the division of labour: generalists, specialists and task allocation.

The evolutionary dynamics of specialization, in the context of the division of labour, are investigated. Individuals associate in groups in which benefits are shared and costs borne individually; each individual is either a generalist who can perform all the necessary tasks, a specialist who performs a sub-set of the necessary tasks, or a parasite who contributes nothing to the group. The implications of the model are explored analytically and through both numerical and Monte Carlo methods. These methods demonstrate the evolution of populations towards stable arrangements of specialists and generalists. The fittest populations are those that divide tasks fairly and associate in large, highly specialized groups. Generalists have a distinct advantage in small groups, but the presence of generalists, ironically, lowers group fitness. Parasites are able to invade both specialized and non-specialized populations. A basic model for the continuous division of labour is also presented, demonstrating a tendency for populations to evolve increasingly unfair divisions of labour. This last result implies that an evolutionary ratchet favours disparity between the workload of specialist populations.

Animals↗

PubMed2025

SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.

BACKGROUND: Persistent SARS-CoV-2 infections in hospitalised immunocompromised individuals are known to facilitate accelerated within-host viral evolution, potentially contributing to the emergence of highly divergent variants. However, little is known about the evolutionary dynamics and transmission risks of persistent infections in the general population. We aimed to characterise the within-host evolution of SARS-CoV-2 during persistent infections identified through a large community surveillance study. METHODS: We used data from the Office for National Statistics COVID-19 Infection Survey (ONS-CIS), a large-scale, longitudinal, population-based surveillance study conducted in the UK from April, 2020, to March, 2023. For this analysis, we focused on infections with high viral load (cycle threshold ≤30) and available genome sequences, from seven major SARS-CoV-2 lineages (alpha, delta, BA.1, BA.2, BA.4, BA.5, and XBB). ONS-CIS participants were randomly selected from the general population and tested regularly by RT-PCR, regardless of symptoms. We defined persistent infections as those with sustained or rebounding high viral RNA titres for 26 days or longer. We examined associated host characteristics and used raw sequence data to identify de novo mutations and estimate within-host synonymous and non-synonymous evolutionary rates across the SARS-CoV-2 genome. FINDINGS: Between Nov 2, 2020, and March 21, 2023, we identified 576 persistent infections with at least two sequences, including 11 alpha, 106 delta, 102 BA.1, 204 BA.2, 16 BA.4, 133 BA.5, and 4 XBB. Persistent infections were more common in males than females (p<0·0001) and individuals older than 60 years (p=0·0027). The median within-host genome-wide evolutionary rate was 7·9 × 10-4 substitutions per site per year (IQR 7·0-9·0 × 10-4), with high inter-individual variability driven largely by non-synonymous mutations, particularly in the N-terminal and receptor-binding domains of the spike protein. Longer infection duration was associated with higher evolutionary rates, while no associations were found with age, sex, vaccination status, previous infection, or virus lineage. We found no clear evidence of transmission beyond the first month of infection in any of the 84 persistent infections lasting 56 days or longer. In total, we identified 379 recurrent mutations, including many with known or predicted negative fitness effects and low prevalence at the population level, as well as de novo reversions to the Wuhan-Hu-1 reference sequence, which were likely under positive selection within those individuals. INTERPRETATION: This study highlights the heterogeneous nature of within-host SARS-CoV-2 evolution in individuals with persistent infection in the community. Notably, a small subset of persistent infections with high viral loads underwent accelerated viral evolution or recurrently acquired hallmark mutations found in novel variants. In addition, onward transmission from a persistent infection during the later stages of infection is likely to be rare. These insights have important implications for prioritising genomic surveillance and managing patients with persistent infections. FUNDING: Department of Health and Social Care.

Humans↗