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Inbreeding, the mating of individuals that are related through common ancestry, is of central importance in evolutionary and conservation biology due to its impacts on individual fitness and population dynamics. However, while advanced genomic approaches have revolutionised the study of inbreeding in animals, genomic studies of inbreeding are rare in plants and lacking in fungi. We investigated global patterns of inbreeding in the prized edible porcini mushroom Boletus edulis using 225 whole genomes from seven lineages distributed across the northern hemisphere. Genomic inbreeding was quantified using runs of homozygosity (ROHs). We found appreciable variation both among and within lineages, with some individuals having over 20% of their genomes in ROHs. Much of this variation could be explained by a combination of elevation and latitude, and to a lesser extent by predicted habitat suitability during the last glacial maximum. In line with this, the majority of ROHs were short, reflecting ancient common ancestry dating back approximately 200-1700 generations ago, while longer ROHs indicative of recent common ancestry (less than approximately 50 generations ago) were infrequent. Our study reveals the inbreeding legacy of major climatic events in a widely distributed forest mutualist, aligning with prevailing theories and empirical studies of the impacts of historical glaciation events on the dominant forest tree species of the northern hemisphere., (© 2024 The Author(s). Molecular Ecology published by John Wiley & Sons Ltd.)

The porcini mushroom family Boletaceae is a diverse, widespread group of ectomycorrhizal (ECM) mushroom-forming fungi that so far has eluded intrafamilial phylogenetic resolution based on morphology and multilocus data sets. In this study, we present a genome-wide molecular data set of 1764 single-copy gene families from a global sampling of 418 Boletaceae specimens. The resulting phylogenetic analysis has strong statistical support for most branches of the tree, including the first statistically robust backbone. The enigmatic Phylloboletellus chloephorus from non-ECM Argentinian subtropical forests was recovered as a new subfamily sister to the core Boletaceae. Time-calibrated branch lengths estimate that the family first arose in the early to mid-Cretaceous and underwent a rapid radiation in the Eocene, possibly when the ECM nutritional mode arose with the emergence and diversification of ECM angiosperms. Biogeographic reconstructions reveal a complex history of vicariance and episodic long-distance dispersal correlated with historical geologic events, including Gondwanan origins and inferred vicariance associated with its disarticulation. Together, this study represents the most comprehensively sampled, data-rich molecular phylogeny of the Boletaceae to date, establishing a foundation for future robust inferences of biogeography in the group.

In the hyperdiverse fungi, the process of speciation is virtually unknown, including for the > 20 000 species of ectomycorrhizal mutualists. To understand this process, we investigated patterns of genome-wide differentiation in the ectomycorrhizal porcini mushroom, Boletus edulis, a globally distributed species complex with broad ecological amplitude. By whole-genome sequencing 160 individuals from across the Northern Hemisphere, we genotyped 792 923 single nucleotide polymorphisms to characterize patterns of genome-wide differentiation and to identify the adaptive processes shaping global population structure. We show that B. edulis exhibits contrasting patterns of genomic divergence between continents, with multiple lineages present across North America, while a single lineage dominates Europe. These geographical lineages are inferred to have diverged 1.62-2.66 million years ago, during a period of climatic upheaval and the onset of glaciation in the Pliocene-Pleistocene boundary. High levels of genomic differentiation were observed among lineages despite evidence of substantial and ongoing introgression. Genome scans, demographic inference, and ecological niche models suggest that genomic differentiation is maintained by environmental adaptation, not physical isolation. Our study uncovers striking patterns of genome-wide differentiation on a global scale and emphasizes the importance of local adaptation and ecologically mediated divergence, rather than prezygotic barriers such as allopatry or genomic incompatibility, in fungal population differentiation., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Background: Few studies have investigated the long-term effects of COVID-19 on cancer patients. Materials & methods: The authors conducted a telephone survey on the long-term symptoms of cancer patients from Guy's Cancer Centre. They compared patients whose symptoms occurred/got worse over 4 weeks after COVID-19 diagnosis (classified as long COVID) with patients who did not develop symptoms or whose symptoms occurred/got worse in the first 4 weeks after diagnosis. Results: The authors analyzed responses from 80 patients with a previous COVID-19 diagnosis; 51.3% (n = 41) developed long COVID. The most common symptoms were fatigue, breathlessness and cognitive impairment. Conclusion: Findings suggest that over half of the cancer population will experience long-term effects after their initial COVID-19 diagnosis. Further studies are required to validate the findings of this study.

Clinical studies have shown that subsets of patients with cancer achieve a significant benefit from Aurora kinase inhibitors, suggesting an urgent need to identify biomarkers for predicting drug response. Chromodomain helicase DNA binding protein 1 (CHD1) is involved in chromatin remodeling, DNA repair, and transcriptional plasticity. Prior studies have demonstrated that CHD1 has distinct expression patterns in cancers with different molecular features, but its impact on drug responsiveness remains understudied. Here, we show that CHD1 promotes the susceptibility of prostate cancer cells to inhibitors targeting Aurora kinases, while depletion of CHD1 impairs their efficacy in vitro and in vivo. Pan-cancer drug sensitivity analyses revealed that high expression of CHD1 was associated with increased sensitivity to Aurora kinase A (AURKA) inhibitors. Mechanistically, KPNA2 served as a direct target of CHD1 and suppressed the interaction of AURKA with the coactivator TPX2, thereby rendering cancer cells more vulnerable to AURKA inhibitors. Consistent with previous research reporting that loss of PTEN elevates CHD1 levels, studies in a genetically engineered mouse model, patient-derived organoids, and patient samples showed that PTEN defects are associated with a better response to AURKA inhibition in advanced prostate cancer. These observations demonstrate that CHD1 plays an important role in modulating Aurora kinases and drug sensitivities, providing new insights into biomarker-driven therapies targeting Aurora kinases for future clinical studies., Significance: CHD1 plays a critical role in controlling AURKA activation and promoting Aurora kinase inhibitor sensitivity, providing a potential clinical biomarker to guide cancer treatment., (©2022 American Association for Cancer Research.)

Objective: The authors monitored positivity rates of asymptomatic SARS-CoV-2 tests during the second wave of COVID-19 at Guy's Cancer Centre. Methods: Logistic regression was used to investigate factors associated with asymptomatic COVID-19 positivity rates between 1 December 2020 and 28 February 2021 (n = 1346). Results: Living 20-40 km and 40-60 km from the alpha variant was associated with a reduced chance of a positive SARS-CoV-2 test compared with 0-20 km (odds ratio [OR]: 0.20; CI: 0.07-0.53 and OR: 0.38; CI: 0.15-0.98, respectively). An increased number of tests was associated with an increased chance of a positive SARS-CoV-2 test (OR: 1.10; CI: 1.04-1.16). Conclusion: The COVID-19 positivity rate of asymptomatic cancer patients is partly due to increased testing, with some contribution from the proximity of the patient population to the epicenter of the alpha variant.

Concerted evolution of the ribosomal DNA array has been studied in numerous eukaryotic taxa, yet is still poorly understood. rDNA genes are repeated dozens to hundreds of times in the eukaryotic genome (Eickbush and Eickbush, 2007) and it is believed that these arrays are homogenized through concerted evolution (Zimmer et al., 1980; Dover, 1993) preventing the accumulation of intragenomic, and intraspecific, variation. However, numerous studies have reported rampant intragenomic and intraspecific variation in the rDNA array (Ganley and Kobayashi, 2011; Naidoo et al., 2013; Hughes and Petersen, 2001; Lindner and Banik, 2011; Li et al., 2013; Lindner et al., 2013; Hughes et al., 2018), contradicting our current understanding of concerted evolution. The internal transcribed spacers (ITS) of the rDNA cistron are the most commonly used DNA barcoding region in Fungi (Schoch et al., 2012), and rely on concerted evolution to homogenize the rDNA array leading to a "barcode gap" (Puillandre et al., 2012). Here we show that in Boletus edulis Bull., ITS intragenomic variation persists at low allele frequencies throughout the rDNA array, this variation does not correlate with genomic relatedness between populations, and rDNA genes may not evolve in a strictly concerted fashion despite the presence of unequal recombination and gene conversion. Under normal assumptions, heterozygous positions found in ITS sequences represent hybridization between populations, yet through allelic mapping of the rDNA array we found numerous heterozygous alleles to be stochastically introgressed throughout, presenting a dishonest signal of gene flow. Moreover, despite the signal of gene flow in ITS, our organisms were highly inbred, indicating a disconnect between true gene flow and barcoding signals. In addition, we show that while the mechanisms of concerted evolution are ongoing in pseudo-heterozygous individuals, they are not fully homogenizing the ITS array. Concerted evolution of the rDNA array may insufficiently homogenize the ITS gene, allowing for misleading signals of gene flow to persist, vastly complicating the use of the ITS locus for DNA barcoding in Fungi., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Loss-of-function studies are key for investigating gene function, and CRISPR technology has made genome editing widely accessible in model organisms and cells. However, conditional gene inactivation in diploid cells is still difficult to achieve. Here, we present CRISPR-FLIP, a strategy that provides an efficient, rapid and scalable method for biallelic conditional gene knockouts in diploid or aneuploid cells, such as pluripotent stem cells, 3D organoids and cell lines, by co-delivery of CRISPR-Cas9 and a universal conditional intronic cassette.