Some of the most damaging tree pathogens can attack woody stems, causing lesions (cankers) that may be lethal. To identify the genomic determinants of wood colonization leading to canker formation, ...we sequenced the genomes of the poplar canker pathogen, Mycosphaerella populorum , and the closely related poplar leaf pathogen, M. populicola . A secondary metabolite cluster unique to M. populorum is fully activated following induction by poplar wood and leaves. In addition, genes encoding hemicellulose-degrading enzymes, peptidases, and metabolite transporters were more abundant and were up-regulated in M. populorum growing on poplar wood-chip medium compared with M. populicola . The secondary gene cluster and several of the carbohydrate degradation genes have the signature of horizontal transfer from ascomycete fungi associated with wood decay and from prokaryotes. Acquisition and maintenance of the gene battery necessary for growth in woody tissues and gene dosage resulting in gene expression reconfiguration appear to be responsible for the adaptation of M. populorum to infect, colonize, and cause mortality on poplar woody stems.
Significance Some of the most damaging tree diseases are caused by pathogens that induce cankers, a stem deformation often lethal. To investigate the cause of this adaptation, we sequenced the genomes of poplar pathogens that do and do not cause cankers. We found a unique cluster of genes that produce secondary metabolites and are co-activated when the canker pathogen is grown on poplar wood and leaves. The gene genealogy is discordant with the species phylogeny, showing a signature of horizontal transfer from fungi associated with wood decay. Furthermore, genes encoding hemicellulose-degrading enzymes are up-regulated on poplar wood chips, with some having been acquired horizontally. We propose that adaptation to colonize poplar woody stems is the result of acquisition of these genes.
As decomposers, fungi are key players in recycling plant material in global carbon cycles. We hypothesized that genomes of early diverging fungi may have inherited pectinases from an ancestral ...species that had been able to extract nutrients from pectin-containing land plants and their algal allies (Streptophytes). We aimed to infer, based on pectinase gene expansions and on the organismal phylogeny, the geological timing of the plant-fungus association. We analyzed 40 fungal genomes, three of which, including Gonapodya prolifera, were sequenced for this study. In the organismal phylogeny from 136 housekeeping loci, Rozella diverged first from all other fungi. Gonapodya prolifera was included among the flagellated, predominantly aquatic fungal species in Chytridiomycota. Sister to Chytridiomycota were the predominantly terrestrial fungi including zygomycota I and zygomycota II, along with the ascomycetes and basidiomycetes that comprise Dikarya. The Gonapodya genome has 27 genes representing five of the seven classes of pectin-specific enzymes known from fungi. Most of these share a common ancestry with pectinases from Dikarya. Indicating functional and sequence similarity, Gonapodya, like many Dikarya, can use pectin as a carbon source for growth in pure culture. Shared pectinases of Dikarya and Gonapodya provide evidence that even ancient aquatic fungi had adapted to extract nutrients from the plants in the green lineage. This implies that 750 million years, the estimated maximum age of origin of the pectin-containing streptophytes represents a maximum age for the divergence of Chytridiomycota from the lineage including Dikarya.
We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related ...phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an α-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation.
Ascomycete yeasts are metabolically diverse, with great potential for biotechnology. Here, we report the comparative genome analysis of 29 taxonomically and biotechnologically important yeasts, ...including 16 newly sequenced. We identify a genetic code change, CUG-Ala, in Pachysolen tannophilus in the clade sister to the known CUG-Ser clade. Our well-resolved yeast phylogeny shows that some traits, such as methylotrophy, are restricted to single clades, whereas others, such as L-rhamnose utilization, have patchy phylogenetic distributions. Gene clusters, with variable organization and distribution, encode many pathways of interest. Genomics can predict some biochemical traits precisely, but the genomic basis of others, such as xylose utilization, remains unresolved. Our data also provide insight into early evolution of ascomycetes. We document the loss of H3K9me2/3 heterochromatin, the origin of ascomycete mating-type switching, and panascomycete synteny at the MAT locus. These data and analyses will facilitate the engineering of efficient biosynthetic and degradative pathways and gateways for genomic manipulation.
Alternative splicing (AS) regulates diverse cellular and developmental functions through alternative protein structures of different isoforms. Alternative exons dominate AS in vertebrates; however, ...very little is known about the extent and function of AS in lower eukaryotes. To understand the role of introns in gene evolution, we examined AS from a green algal and five fungal genomes using a novel EST-based gene-modeling algorithm (COMBEST).
AS from each genome was classified with COMBEST that maps EST sequences to genomes to build gene models. Various aspects of AS were analyzed through statistical methods. The interplay of intron 3n length, phase, coding property, and intron retention (RI) were examined with Chi-square testing.
With 3 to 834 times EST coverage, we identified up to 73% of AS in intron-containing genes and found preponderance of RI among 11 types of AS. The number of exons, expression level, and maximum intron length correlated with number of AS per gene (NAG), and intron-rich genes suppressed AS. Genes with AS were more ancient, and AS was conserved among fungal genomes. Among stopless introns, non-retained introns (NRI) avoided, but major RI preferred 3n length. In contrast, stop-containing introns showed uniform distribution among 3n, 3n+1, and 3n+2 lengths. We found a clue to the intron phase enigma: it was the coding function of introns involved in AS that dictates the intron phase bias.
Majority of AS is non-functional, and the extent of AS is suppressed for intron-rich genes. RI through 3n length, stop codon, and phase bias bridges the transition from functionless to functional alternative isoforms.
Tumor histology is an important predictor of therapeutic response and outcomes in lung cancer. Tissue sampling for pathologist review is the most reliable method for histology classification, ...however, recent advances in deep learning for medical image analysis allude to the utility of radiologic data in further describing disease characteristics and for risk stratification. In this study, we propose a radiomics approach to predicting non-small cell lung cancer (NSCLC) tumor histology from non-invasive standard-of-care computed tomography (CT) data. We trained and validated convolutional neural networks (CNNs) on a dataset comprising 311 early-stage NSCLC patients receiving surgical treatment at Massachusetts General Hospital (MGH), with a focus on the two most common histological types: adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC). The CNNs were able to predict tumor histology with an AUC of 0.71(p = 0.018). We also found that using machine learning classifiers such as k-nearest neighbors (kNN) and support vector machine (SVM) on CNN-derived quantitative radiomics features yielded comparable discriminative performance, with AUC of up to 0.71 (p = 0.017). Our best performing CNN functioned as a robust probabilistic classifier in heterogeneous test sets, with qualitatively interpretable visual explanations to its predictions. Deep learning based radiomics can identify histological phenotypes in lung cancer. It has the potential to augment existing approaches and serve as a corrective aid for diagnosticians.
The prevalence of child sexual abuse (CSA) in the population has been poorly described in developing countries. Population data on child sexual abuse in Brazil is very limited. This paper aims to ...estimate lifetime prevalence of child sexual abuse and associated factors in a representative sample of the population aged 14 and over in a city of southern Brazil.
A two-stage sampling strategy was used and individuals were invited to respond to a confidential questionnaire in their households. CSA was defined as non-consensual oral-genital, genital-genital, genital-rectal, hand-genital, hand-rectal, or hand-breast contact/intercourse between ages 0 and 18. Associations between socio-demographic variables and CSA, before and after age 12, were estimated through multinomial regression.
Complete data were available for 1936 respondents from 1040 households. Prevalence of CSA among girls (5.6% 95%CI 4.8;7.5) was higher than among boys (1.6% 95%CI 0.9;2.6). Boys experienced CSA at younger ages than girls and 60% of all reported CSA happened before age 12. Physical abuse was frequently associated with CSA at younger (OR 5.6 95%CI 2.5;12.3) and older (OR 9.4 95%CI 4.5;18.7) ages. CSA after age 12 was associated with an increased number of sexual partners in the last 2 months.
Results suggest that CSA takes place at young ages and is associated with physical violence, making it more likely to have serious health and developmental consequences. Except for gender, no other socio-demographic characteristic identified high-risk sub-populations.
ENVIRONMENTAL SCIENCES Correction for “Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche,” by Emmanuelle Morin, ...Annegret Kohler, Adam R. Baker, Marie Foulongne-Oriol, Vincent Lombard, Laszlo G. Nagy, Robin A. Ohm, Aleksandrina Patyshakuliyeva, Annick Brun, Andrea L. Aerts, Andrew M. Bailey, Christophe Billette, Pedro M. Coutinho, Greg Deakin, Harshavardhan Doddapaneni, Dimitrios Floudas, Jane Grimwood, Kristiina Hildén, Ursula Kües, Kurt M. LaButti, Alla Lapidus, Erika A. Lindquist, Susan M. Lucas, Claude Murat, Robert W. Riley, Asaf A. Salamov, Jeremy Schmutz, Venkataramanan Subramanian, Han A. B. Wösten, Jianping Xu, Daniel C. Eastwood, Gary D. Foster, Anton S. M. Sonnenberg, Dan Cullen, Ronald P. de Vries, Taina Lundell, David S. Hibbett, Bernard Henrissat, Kerry S. Burton, Richard W. Kerrigan, Michael P. Challen, Igor V. Grigoriev, and Francis Martin, which appeared in issue 43, October 23, 2012, of Proc Natl Acad Sci USA (109:17501–17506; first published October 8, 2012; 10.1073/pnas.1206847109). The authors note that the following statement should be added to the Acknowledgments: “G.D. is a PhD student funded by the Teagasc Walsh Fellowship scheme and jointly supervised by K.S.B., and HM Grogan, Teagasc, Ireland.”
Brown rot decay removes cellulose and hemicellulose from wood—residual lignin contributing up to 30% of forest soil carbon—and is derived from an ancestral white rot saprotrophy in which both lignin ...and cellulose are decomposed. Comparative and functional genomics of the "dry rot" fungus Serpula lacrymans, derived from forest ancestors, demonstrated that the evolution of both ectomycorrhizal biotrophy and brown rot saprotrophy were accompanied by reductions and losses in specific protein families, suggesting adaptation to an intercellular interaction with plant tissue. Transcriptome and proteome analysis also identified differences in wood decomposition in S. lacrymans relative to the brown rot Postia placenta. Furthermore, fungal nutritional mode diversification suggests that the boreal forest biome originated via genetic coevolution of above- and below-ground biota.
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