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PubMed2025

Comparative genomic analysis of Acer tsinglingense and A. davidii provides insights into nervonic acid biosynthesis, population evolution and genome vulnerability of endangered A. tsinglingense.

Global biodiversity is facing threats from climate change, habitat fragmentation, and anthropogenic activities-pressures that particularly endanger endemic and narrowly distributed species. In this study, the high-quality chromosome-level genomes of two ecologically divergent maples were assembled: the endangered and range-restricted Acer tsinglingense (791.40 Mb) and its widespread congener Acer davidii (1291.99 Mb). Phylogenomic analysis indicates that the two species diverged ~16.3 million years ago, with A. tsinglingense showing notable gene family expansions in secondary metabolite pathways. Notably, the 3-ketoacyl-CoA synthase gene family, which is involved in nervonic acid biosynthesis, underwent significant expansion and tandem duplication in A. tsinglingense, exhibiting high expression in buds. Population genomic analysis revealed that, compared with the widely distributed A. davidii, A. tsinglingense possesses lower genetic diversity, higher harmful mutation load, and signatures of a severe population bottleneck during the Late Pleistocene. Genome-environment association analysis further identified climate-adaptive genomic variations linked to five key environmental factors and projected potential genomic offsets under future climate scenarios. The southern lineage of A. tsinglingense exhibited greater climate sensitivity and genomic vulnerability under strong selective pressures, underscoring its importance as a conservation priority. Our research reveals that metabolic specializations in A. tsinglingense (such as the synthesis of nervonic acid) may confer competitive advantages in specific habitats. However, factors including its restricted distribution, historical population bottlenecks, and accumulated genetic load severely constrain its evolutionary potential to cope with rapid climate change. These findings emphasize the importance of elucidating the genomic basis and mechanisms of endangerment in metabolically specialized and threatened plant species to inform effective conservation strategies.

Genome, Plant↗
PubMed2025

Common gardens reveal genomic susceptibility and vulnerability to climate change in Eucalyptus.

Accelerated global climate change and increased species introduction across international scales have raised concerns about the potential for trees to experience maladaptation or lagging adaptation in response to these environmental shifts. However, our knowledge regarding the relationship between the genomic metrics used to predict maladaptation and actual fitness proxies in trees remains limited. Here, we present a population genomic analysis of 295 families from 28 provenances of Eucalyptus pellita, a widely cultivated fast-growing tree species, and conducted two common garden experiments. Genomic susceptibility encompassing individual heterozygosity (H), genomic inbreeding (FROH), and genomic load (inferred from deleterious mutations) exhibited distinct geographic patterns, shedding light on the origin and evolutionary history of E. pellita. The genetic basis of local adaptation was elucidated through genotype-environment associations and genome-wide association studies, including 198 loci associated with climate and 2388 loci regulating different traits. Furthermore, Australian provenances have higher genomic vulnerability under prospective climate alterations than Papua New Guinea and Indonesia provenances. By integrating phenotypic data across two common gardens, the relationship between leaf functional traits and predicted metrics of maladaptation was closer than growth attributes. Notably, pronounced natural selection signals linked to leaf morphogenesis have been identified by comparing two lineages spanning the oceans. This study underscores the immense potential of leveraging genomic susceptibility and genomic vulnerability to decipher the local (mal)adaptation of forest trees.

Eucalyptus↗
PubMed2024

Global quantification of off-target activity by base editors.

Base editors are engineered deaminases combined with CRISPR components. These engineered deaminases are designed to target specific sites within DNA or RNA to make a precise change in the molecule. In therapeutics, they hold promise for correcting mutations associated with genetic diseases. However, a key challenge is minimizing unintended edits at off-target sites, which could lead to harmful mutations. Researchers are actively addressing this concern through a variety of optimization efforts that aim to improve the precision of base editors and minimize off-target activity. Here, we examine the various types of off-target activity, and the methods used to evaluate them. Current methods for finding off-target activity focus on identifying similar sequences in the genome or in the transcriptome, assuming the guide RNA misdirects the editor. The main method presented here, that was originally developed to quantify editing levels mediated by the ADAR enzyme, takes a different approach, investigating the inherent activity of base editors themselves, which might lead to off-target edits beyond sequence similarity. The editing index tool quantifies global off-target editing, eliminates the need to detect individual off-target sites, and allows for assessment of the global load of mutations.

Gene Editing↗
PubMed2026

High levels of mitotic gene conversion are needed to effectively purge deleterious mutations in asexual organisms.

Self-fertilisation and asexual reproduction are both hypothesised to cause long-term extinction due to inefficient selection against deleterious mutations. Self-fertilisation can counter these effects through creating homozygous genotypes and purging deleterious mutations. Although complete asexuality lacks meiotic gene exchange, mitotic gene conversion creates homozygous regions that could limit deleterious mutation accumulation in an analogous manner. We compare mutation accumulation in self-fertilising and facultative sexual populations subject to mitotic gene conversion, and quantify the efficacy of purging in the latter. We first show analytically that purging is most effective with high levels of asexuality and gene conversion, and when deleterious mutations are recessive. We further show using simulations that, when mitotic gene conversion becomes sufficiently high in obligate asexuals, there is a reduction in the mutation count and a jump in homozygosity, reflecting purging. However, this mechanism is not necessarily as efficient at purging under high self-fertilisation, and elevated rates of mitotic gene conversion seem to be needed for widespread purging compared to empirical estimates. If gene conversion rates are allowed to evolve, then elevated rates that increase mean fitness can arise, but only if there is sufficient variance in the gene conversion rate. Conversely, if gene conversion rates are already high and rates are not constrained then they will slightly decrease, reducing mean fitness.

Self-fertilisation↗
PubMed2025

Compensatory Evolution Following Deleterious Episodes of GC-biased Gene Conversion in Rodents.

GC-biased gene conversion (gBGC) is a widespread evolutionary force associated with meiotic recombination that favors the accumulation of deleterious AT to GC substitutions in proteins, moving them away from their fitness optimum. In many mammals, recombination hotspots have a rapid turnover, leading to episodic gBGC, with the accumulation of deleterious mutations stopping when the recombination hotspot dies. Selection is therefore expected to act to repair the damage caused by gBGC episodes through compensatory evolution. However, this process has never been studied or quantified so far. Here, we analyzed the nucleotide substitution pattern in coding sequences of a highly diversified group of Murinae rodents. Using phylogenetic analyses of about 70,000 coding exons, we identified numerous exon-specific, lineage-specific gBGC episodes, characterized by a clustering of synonymous AT to GC substitutions and by an increasing rate of nonsynonymous AT to GC substitutions, many of which are potentially deleterious. Analyzing the molecular evolution of the affected exons in downstream lineages, we found evidence for pervasive compensatory evolution after deleterious gBGC episodes. Compensation appears to occur rapidly after the end of the episode and to be driven by the standing genetic variation rather than new mutations. Our results demonstrate the impact of gBGC on the evolution of amino-acid sequences and underline the key role of epistasis in protein adaptation. This study contributes to a growing body of literature emphasizing that adaptive mutations, which arise in response to environmental changes, are just 1 subset of beneficial mutations, alongside mutations resulting from oscillations around the fitness optimum.

Gene Conversion↗
PubMed2025

Sexual selection, genomic evolution and population fitness in Drosophila pseudoobscura.

Sexual selection shapes the genome in unique ways. It is also likely to have significant fitness consequences, such as purging deleterious mutations from the genome or conversely maintaining genetic load in a population via sexual conflict. Here, we examined what the influence of sexual selection has on genomic variation potentially underlying population fitness using experimentally evolved Drosophila pseudoobscura populations. Sexual selection was manipulated by keeping replicate lines in elevated polyandry or strict monogamy for approximately 200 generations followed by individual-based sequencing. Using pi (π), fixation index (Fst)and recombination rate measures, we confirmed signatures of selection were not dispersed but mainly localized to the third and X chromosome. Overall mutational load was similar between lines but our analysis of the distribution of fitness effects revealed considerable variation between lines and chromosomes. Furthermore, we found that the distribution of transposable elements differs between the lines, with a higher load in monogamous lines. Our results suggest that complex interactions between purifying selection and sexual conflict are shaping the genome, particularly on chromosome 3 and the sex chromosome; sexual selection influences divergence across chromosomes but in a more complex way than proposed by simple 'purging' of deleterious loci.

Animals↗
PubMed2025

Inbreeding load in finite populations from dominant and overdominant mutations.

Inbreeding depression is a widespread phenomenon that reflects the burden of deleterious effects hidden in heterozygosis in non-inbred populations but exposed in homozygosis in inbred individuals, known as inbreeding load (B). This load can be due to partially or fully recessive deleterious mutations (dominance model) or to heterozygote advantage (overdominance model, where both homozygotes are deleterious relative to the heterozygote). There are many studies addressing the changes in inbreeding load in finite populations assuming the dominance model. However, the contribution of overdominance to inbreeding depression has been focused on infinite-size populations. We carried out computer simulations to investigate the joint impact of dominant and pure overdominant mutations on inbreeding load, both for self-fertilizing populations and for panmictic populations suffering from a drastic bottleneck. We found that the overdominant inbreeding load can be substantially reduced by drift even for symmetrical overdominance, at least when considering mutations of small effect. For panmictic bottlenecked populations, the reduction in inbreeding load under dominance and overdominance loci cannot be easily distinguished. However, while purging depletes inbreeding load from dominant loci, slowing inbreeding depression and leading to partial fitness recovery, for overdominant loci fitness declines monotonically.

Inbreeding↗
PubMed2025

Identification of a Highly Cooperative PROTAC Degrader Targeting GTP-Loaded KRAS(On) Alleles.

Kirsten rat sarcoma viral oncogene homologue (KRAS) is a frequently mutated oncogene in multiple types of cancer and is a high priority target for oncology drug development. There are many different KRAS mutations, including mutations that favor the GTP-loaded hydrolysis-incompetent "active" state of KRAS, KRAS(on), that can lead to tumorigenesis. However, small molecule interventions thus far have predominantly targeted single mutations of "inactive" GDP-loaded KRAS, KRAS(off), such as KRASG12C. Here, we address this gap through the development of heterobifunctional VHL-based PROTACs capable of engaging and degrading KRAS(on), thus addressing a wider range of KRAS mutations. By studying ternary complex affinity, stability, and binding modes using SPR and X-ray cocrystal structures, we identified PROTACs that exhibit high positive cooperativity in forming ternary complexes with VHL and GCP-loaded KRAS as representative of KRAS(on) variants. Degrader activity profiling in relevant cancer cells supported the discovery of ACBI4, a PROTAC which forms a highly stable and cooperative ternary complex between VHL and GTP-bound KRAS and which potently degrades KRASG12R, leading to antiproliferative effect in KRAS mutant-driven cancer cells. ACBI4 provides a new chemical tool for studying the impact of degrading KRAS(on) mutants, which is not possible with current pan-KRAS inhibitors or degraders.

Proto-Oncogene Proteins p21(ras)↗
PubMed2025

Unraveling the Role of Mutations Outside the Basal Promoter and Precore Regions in the HBeAg-Negative Stage of Chronic Hepatitis B.

Hepatitis B e antigen (HBeAg) seroconversion is a crucial event in the natural history of chronic hepatitis B virus (HBV) infection, marked by a significant decrease in viral load and the emergence of mutations that suppress HBeAg expression. However, these mutations alone do not fully account for the reduction in viral load. This study investigated the biological features and pathogenic roles of mutations outside the basal core promoter (BCP) and precore regions during the HBeAg-negative stage of chronic infection. Full-length HBV genomes from HBeAg-positive (n = 180) and HBeAg-negative (n = 328) genotype D datasets were analyzed, revealing significantly higher genomic heterogeneity in HBeAg-negative sequences compared with HBeAg-positive genomes (50.4 ± 16.0 vs. 26.6 ± 10.5 nucleotide changes per genome). Twenty-six hotspot amino acid mutations associated with the HBeAg-negative stage were identified, with over half located in the Core region. Subsequently, full-length HBV genomes from six HBeAg-negative patient-derived serum samples were obtained by PCR amplification followed by Sanger sequencing. Infectious clones generated from these genomes, each carrying between 21 and 66 amino acid substitutions, were characterized, showing that mutations in this stage differentially affected viral fitness in vitro by up- or downregulating HBV-DNA levels (ranging from 0.2 to 5 times those of the wild-type isolate), modulating capsid assembly, and altering the expression, secretion, and subcellular localization of viral proteins. In conclusion, while mutations in the BCP and precore regions are the primary drivers of HBeAg seroconversion, mutations outside these regions significantly influence HBV biology and potentially contribute to viral pathogenicity, underscoring the complex interplay between host and virus during the HBeAg-negative stage of chronic infection.

Humans↗
PubMed1975

Spontaneous recessive lethal mutations in the mouse.

The estimation of the load of recessive lethals in our inbred CBA strain is based on samples drawn from 1964 to 1971. 407 control F1 males were back-crossed to their daughters. The first examined females which for each F1 male gave 50 implants were included in the test. their rate of intra-uterine death was compared to that from lethal-free males. The distribution of the number of F1 males according to the number of dead in the first 50 implants were compared to a model of lüning. Three estimates of the proportion of lethal heterozygotes gave 4.2, 5.35 and 6.2% respectively. From the way the inbred strain was kept it was estimated that the mean load among F1 males was 11.5mu (mu equal to mutation rate per gamete). These data indicate that about 0.5% lethals occur per gamete with an upper limit of 1%. Comparisons are made with previous estimates of the spontaneous rate of lethal mutations per gamete. The low proportion of lethal mutations indicate that the number of loci giving lethal mutations is low. Both spontaneous and induced mutations give similar low numbers, more than one order of magnitude below the number commonly assumed. The uncertainties are stressed of estimating risk by multiplying mutation rate per locus and assumed number of loci.

Animals↗
PubMed2022

Nonsense-mediated RNA decay: an emerging modulator of malignancy.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that selectively degrades RNAs harbouring truncating mutations that prematurely terminate translation, including nonsense, frameshift and some splice-site mutations. Recent studies show that NMD shapes the mutational landscape of tumours by selecting for mutations that tend to downregulate the expression of tumour suppressor genes but not oncogenes. This suggests that NMD can benefit tumours, a notion further supported by the finding that mRNAs encoding immunogenic neoantigen peptides are typically targeted for decay by NMD. Together, this raises the possibility that NMD-inhibitory therapy could be of therapeutic benefit against many tumour types, including those with a high load of neoantigen-generating mutations. Complicating this scenario is the evidence that NMD can also be detrimental for many tumour types, and consequently tumours often have perturbed NMD. NMD may suppress tumour generation and progression by degrading subsets of specific normal mRNAs, including those encoding stress-response proteins, signalling factors and other proteins beneficial for tumours, as well as pro-tumour non-coding RNAs. Together, these findings suggest that NMD-modulatory therapy has the potential to provide widespread therapeutic benefit against diverse tumour types. However, whether NMD should be stimulated or repressed requires careful analysis of the tumour to be treated.

Humans↗
PubMed2021

Drug resistance mutations in HIV provirus are associated with defective proviral genomes with hypermutation.

BACKGROUND: HIV proviral sequencing overcomes the limit of plasma viral load requirement by detecting all the 'archived mutations', but the clinical relevance remains to be evaluated. METHODS: We included 25 participants with available proviral sequences (both intact and defective sequences available) and utilized the genotypic sensitivity score (GSS) to evaluate the level of resistance in their provirus and plasma virus. Defective sequences were further categorized as sequences with and without hypermutations. Personalized GSS score and total GSS score were calculated to evaluate the level of resistance to a whole panel of antiretroviral therapies and to certain antiretroviral therapy that a participant was using. The rate of sequences with drug resistance mutations (DRMs) within each sequence compartment (intact, defective and plasma viral sequences) was calculated for each participant. RESULTS: Defective proviral sequences harbored more DRMs than other sequence compartments, with a median DRM rate of 0.25 compared with intact sequences (0.0, P&#x200a;=&#x200a;0.014) and plasma sequences (0.095, P&#x200a;=&#x200a;0.30). Defective sequences with hypermutations were the major source of DRMs, with a median DRM rate of 1.0 compared with defective sequences without hypermutations (0.042, P&#x200a;<&#x200a;0.001). Certain Apolipoprotein B Editing Complex 3-related DRMs including reverse transcriptase gene mutations M184I, E138K, M230I, G190E and protease gene mutations M46I, D30N were enriched in hypermutated sequences but not in intact sequences or plasma sequences. All the hypermutated sequences had premature stop codons due to Apolipoprotein B Editing Complex 3. CONCLUSION: Proviral sequencing may overestimate DRMs as a result of hypermutations. Removing hypermutated sequences is essential in the interpretation of proviral drug resistance testing.

Anti-HIV Agents↗
PubMed1977

Colchester revisited: a genetic study of mental defect.

This reanalysis of a classic survey leads to inferences about design of genetic studies, resolution of heterogeneity, and the role of autosomal and sex-linked genes in mental retardation, which is no longer refractory to segregation analysis. By discriminating between sociofamilial and biological types we estimate that at least 351 autosomal loci can produce mental retardation, with an inbred load of 0.83 detrimental equivalents and a mutation rate of 0.008 per gamete, or less than 2.4 X 10(-5) per locus. The distribution of probands was estimated as: 7 per cent medical, 60 per cent sociofamilial, and 33 per cent biological. Simple genetic mechanisms account for virtually all the biological category. Within the sociofamilial group cultural inheritance and polygenes could not be resolved.

Consanguinity↗
PubMed2026

Cohesin promotes genomic stability by suppressing unequal sister chromatid exchange.

The protein complex cohesin plays critical roles in genomic stability by tethering together sister chromatids at their pericentric regions and along their arms from S phase until anaphase. Cohesin-mediated pericentric cohesion prevents aneuploidy by ensuring bipolar attachment of sister kinetochores. Arm cohesion prevents loss of heterozygosity by biasing DNA repair via recombination between sister chromatids rather than between homologs. Here, we investigate in yeast whether cohesin also enhances genomic stability by suppressing unequal sister chromatid exchange (USCE) between repetitive sequences. In wild-type cells, the USCE rate between repeats 4kb apart (proximal) was 15X higher than repeats 68kb apart (distal). The USCE between distal repeats but not proximal repeats increased 4 to 7-fold in mutants with altered cohesin subunits or auxiliary factors. The level of increased distal USCE corresponded with reduced arm cohesion, reduced density of cohesion arm sites, and higher sister loci mobility. Our results suggest that high density of arm cohesion sites confines repair of DNA damage to local sequences. When the density of cohesion sites decreases, sister chromatid sequences are less confined, thereby enhancing distal repeat interactions and USCE. Another set of mutations disrupted both DNA replication and cohesin loading at the replication fork during S phase. Remarkably, distal USCE in these mutants increased approximately 100-fold and was 6-fold more likely than proximal USCE. This preferential hyperdistal USCE can be explained by an aberrant sister-chromatid structure that is normally prevented by proper coupling of cohesin function and replication.

Journal Article↗
PubMed2023

Utilizing evolutionary conservation to detect deleterious mutations and improve genomic prediction in cassava.

INTRODUCTION: Cassava (Manihot esculenta) is an annual root crop which provides the major source of calories for over half a billion people around the world. Since its domestication ~10,000 years ago, cassava has been largely clonally propagated through stem cuttings. Minimal sexual recombination has led to an accumulation of deleterious mutations made evident by heavy inbreeding depression. METHODS: To locate and characterize these deleterious mutations, and to measure selection pressure across the cassava genome, we aligned 52 related Euphorbiaceae and other related species representing millions of years of evolution. With single base-pair resolution of genetic conservation, we used protein structure models, amino acid impact, and evolutionary conservation across the Euphorbiaceae to estimate evolutionary constraint. With known deleterious mutations, we aimed to improve genomic evaluations of plant performance through genomic prediction. We first tested this hypothesis through simulation utilizing multi-kernel GBLUP to predict simulated phenotypes across separate populations of cassava. RESULTS: Simulations showed a sizable increase of prediction accuracy when incorporating functional variants in the model when the trait was determined by<100 quantitative trait loci (QTL). Utilizing deleterious mutations and functional weights informed through evolutionary conservation, we saw improvements in genomic prediction accuracy that were dependent on trait and prediction. CONCLUSION: We showed the potential for using evolutionary information to track functional variation across the genome, in order to improve whole genome trait prediction. We anticipate that continued work to improve genotype accuracy and deleterious mutation assessment will lead to improved genomic assessments of cassava clones.

cassava (Manihot esculenta)↗
PubMed2026

A two-factor authentication mechanism licenses pilins for pilus assembly in gram-positive bacteria.

Gram-positive bacteria display virulence-associated pili that facilitate adhesion and biofilm formation. These pili are covalently polymerized by class C sortase enzymes, which selectively recognize their cognate pilin substrates amid numerous cell wall sorting signal (CWSS)-bearing proteins. The molecular basis for this stringent substrate specificity has remained unclear. Here, we develop a rapid, quantitative fluorescence-activated cell sorting assay to monitor pilus assembly in Corynebacterium diphtheriae, enabling high-throughput analysis of SpaA pilin and SrtA sortase variants. Using this platform, together with molecular modeling and dynamics simulations, we show that SrtA engages nearly the entire SpaA CWSS to form a membrane-embedded complex that incorporates not only the LPXTG motif but also its connector and transmembrane helix elements. Formation of this interface displaces an inhibitory active-site lid and activates the enzyme to load the pilin substrate. Systematic CWSS swapping experiments and deep mutational scanning further support this model, demonstrating that noncognate pilins are excluded because they fail to form the required interface. Conversely, SrtA variants with an artificially unlatched lid bypass the need for this interface, indicating that membrane-driven complex formation is important for substrate licensing. Together, these findings define a "two-factor authentication" mechanism for pilus assembly in gram-positive bacteria: class C sortases first verify pilin identity by forming a membrane-embedded interface that activates the enzyme, then they recognize the LPXTG motif to initiate loading and crosslinking. This work provides a unified molecular framework for selective pilin incorporation in gram-positive bacteria and identifies potential vulnerabilities in the licensing machinery that may be exploited therapeutically.

Fimbriae, Bacterial↗
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 &#x2264;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&#xb7;0001) and individuals older than 60 years (p=0&#xb7;0027). The median within-host genome-wide evolutionary rate was 7&#xb7;9&#x2009;&#xd7;&#x2009;10-4 substitutions per site per year (IQR 7&#xb7;0-9&#xb7;0&#x2009;&#xd7;&#x2009;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↗