| 1. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 2. |
- Hodgins-Davis, Andrea, et al.
(författare)
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Abundant Gene-by-Environment Interactions in Gene Expression Reaction Norms to Copper within Saccharomyces cerevisiae.
- 2012
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 4:11, s. 1061-79
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation for plastic phenotypes potentially contributes phenotypic variation to populations that can be selected during adaptation to novel ecological contexts. However, the basis and extent of plastic variation that manifests in diverse environments remains elusive. Here, we characterize copper reaction norms for mRNA abundance among five Saccharomyces cerevisiae strains to 1) describe population variation across the full range of ecologically relevant copper concentrations, from starvation to toxicity, and 2) to test the hypothesis that plastic networks exhibit increased population variation for gene expression. We find that although the vast majority of the variation is small in magnitude (considerably <2-fold), not just some, but most genes demonstrate variable expression across environments, across genetic backgrounds, or both. Plastically expressed genes included both genes regulated directly by copper-binding transcription factors Mac1 and Ace1 and genes indirectly responding to the downstream metabolic consequences of the copper gradient, particularly genes involved in copper, iron, and sulfur homeostasis. Copper-regulated gene networks exhibited more similar behavior within the population in environments where those networks have a large impact on fitness. Nevertheless, expression variation in genes like Cup1, important to surviving copper stress, was linked with variation in mitotic fitness and in the breadth of differential expression across the genome. By revealing a broader and deeper range of population variation, our results provide further evidence for the interconnectedness of genome-wide mRNA levels, their dependence on environmental context and genetic background, and the abundance of variation in gene expression that can contribute to future evolution.
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| 3. |
- Johannesson, Hanna, et al.
(författare)
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Concerted evolution in the rpeats of an immunomodulating cell surface protein, SOWgp, of the human pathogenic fungi Coccidioides immitis and C. posadasii.
- 2005
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Ingår i: Genetics.
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Tidskriftsartikel (refereegranskat)abstract
- Genome dynamics that allow pathogens to escape host immune responses are fundamental to our understanding of host-pathogen interactions. Here we present the first population-based study of the process of concerted evolution in the repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the immunodominant protein in the parasitic phase of the human pathogenic fungi Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains representing the geographic ranges of the two Coccidioides species. By using phylogenetic and genetic distance analyses we discovered that the repetitive part of SOWgp evolves by concerted evolution, predominantly by the mechanism of unequal crossing over. We implemented a mathematical model originally developed for multigene families to estimate the rate of homogenization and recombination of the repetitive array, and the results indicate that the pattern of concerted evolution is a result of homogenization of repeat units proceeding at a rate close to the nucleotide point mutation rate. The release of the SOWgp molecules by the pathogen during proliferation may mislead the host: we speculate that the pathogen benefits from concerted evolution of repeated domains in SOWgp by an enhanced ability to misdirect the host’s immune system.
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| 4. |
- Nygren, Kristiina, et al.
(författare)
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Analyses of expressed sequence tags in Neurospora reveal rapid evolution of genes associated with the early stages of sexual reproduction in fungi
- 2012
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 12, s. 229-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The broadly accepted pattern of rapid evolution of reproductive genes is primarily based on studies of animal systems, although several examples of rapidly evolving genes involved in reproduction are found in diverse additional taxa. In fungi, genes involved in mate recognition have been found to evolve rapidly. However, the examples are too few to draw conclusions on a genome scale. Results: In this study, we performed microarray hybridizations between RNA from sexual and vegetative tissues of two strains of the heterothallic (self-sterile) filamentous ascomycete Neurospora intermedia, to identify a set of sex-associated genes in this species. We aligned Expressed Sequence Tags (ESTs) from sexual and vegetative tissue of N. intermedia to orthologs from three closely related species: N. crassa, N. discreta and N. tetrasperma. The resulting four-species alignments provided a dataset for molecular evolutionary analyses. Our results confirm a general pattern of rapid evolution of fungal sex-associated genes, compared to control genes with constitutive expression or a high relative expression during vegetative growth. Among the rapidly evolving sex-associated genes, we identified candidates that could be of importance for mating or fruiting-body development. Analyses of five of these candidate genes from additional species of heterothallic Neurospora revealed that three of them evolve under positive selection. Conclusions: Taken together, our study represents a novel finding of a genome-wide pattern of rapid evolution of sex-associated genes in the fungal kingdom, and provides a list of candidate genes important for reproductive isolation in Neurospora.
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| 5. |
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| 6. |
- Samils, Nicklas, et al.
(författare)
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Sex-linked transcriptional divergence in the hermaphrodite fungus Neurospora tetrasperma
- 2013
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 280:1764, s. 20130862-
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Tidskriftsartikel (refereegranskat)abstract
- In the filamentous ascomycete Neurospora tetrasperma, a large (approx. 7 Mbp) region of suppressed recombination surrounds the mating-type (mat) locus. While the remainder of the genome is largely homoallelic, this region of recombinational suppression, extending over 1500 genes, is associated with sequence divergence. Here, we used microarrays to examine how the molecular phenotype of gene expression level is linked to this divergent region, and thus to the mating type. Culturing N. tetrasperma on agar media that induce sexual/female or vegetative/male tissue, we found 196 genes significantly differentially expressed between mat A and mat a mating types. Our data show that the genes exhibiting mat-linked expression are enriched in the region genetically linked to mating type, and sequence and expression divergence are positively correlated. Our results indicate that the phenotype of mat A strains is optimized for traits promoting sexual/female development and the phenotype of mat a strains for vegetative/male development. This discovery of differentially expressed genes associated with mating type provides a link between genotypic and phenotypic divergence in this taxon and illustrates a fungal analogue to sexual dimorphism found among animals and plants.
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| 7. |
- Wang, Zheng, 1980, et al.
(författare)
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Future perspectives and challenges of fungal systematics in the age of big data
- 2016
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Ingår i: Biology of Microfungi. - Switzerland : Springer International Publishing. - 9783319291352 ; , s. 25-46
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Bokkapitel (refereegranskat)abstract
- Mycological research, especially research on fungal evolution and ecology, requires a robust and detailed fungal classification and phylogeny to facilitate efficient and informative communication among mycologists as well as for comparative biology relevant to the larger bioscience community. The field of fungal systematics has undergone numerous revisions recently, from early morphological classifications to an integrative taxonomy that is increasingly reliant on molecular phylogeny. These revisions have taken place at a range of taxonomic ranks, fueled by advances surmounting two major challenges, namely, adequate and balanced sampling of genetic markers and taxa and reinterpretation of phylogenetic informativeness of numerous morphological and ecological characters. The Assembling the Fungal Tree of Life (AFTOL) projects reflected a corresponding surge of collaborative effort in fungal molecular phylogeny using PCR and Sanger sequencing. Here we review recent progress in fungal systematics after AFTOL, in the post-Sanger age, and discuss the future fungal systematics that is emerging as a result of the extraordinary volume of data being gathered by high-throughput sequencing. We examine how environmental DNA surveys, sequence-based classification, and phylogenomics and phylotranscriptomics can impact fungal systematics and point out that sequenced fungal genomes could significantly improve multi-marker phylogenetic inference at a range of levels of fungal systematics by facilitating application of phylogenetically informative experimental design. We argue that it is time to integrate fungal systematics, genome-enabled mycology, and other dimensions of fungal research within the framework of evolutionary biology.
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| 8. |
- Wang, Zheng, et al.
(författare)
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Sex-specific gene expression during asexual development of Neurospora crassa
- 2012
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1087-1845 .- 1096-0937. ; 49:7, s. 533-543
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Tidskriftsartikel (refereegranskat)abstract
- The impact of loci that determine sexual identity upon the asexual, dominant stage of fungal life history has been well studied. To investigate their impact, expression differences between strains of different mating type during asexual development were assayed, with RNA sampled from otherwise largely isogenic mat A and mat a strains of Neurospora crassa at early, middle, and late clonal stages of development. We observed significant differences in overall gene expression between mating types across clonal development, especially at late development stages. The expression levels of mating-type genes and pheromone genes were assayed by reverse transcription and quantitative PCR, revealing expression of pheromone and receptor genes in strains of both mating types in all development stages, and revealing that mating type (mat) genes were increasingly expressed over the course of asexual development. Interestingly, among differentially expressed genes, the mat A genotype more frequently exhibited a higher expression level than mat a, and demonstrated greater transcriptional regulatory dynamism. Significant up-regulation of expression was observed for many late light-responsive genes at late asexual development stages. Further investigation of the impact of light and the roles of light response genes in asexual development of both mating types are warranted.
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| 9. |
- Wang, Zheng, 1980, et al.
(författare)
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Tasting soil fungal diversity with earth tongues: phylogenetic test of SATé alignments for environmental ITS data
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- An abundance of novel fungal lineages have been indicated by DNA sequencing of the nuclear ribosomal ITS region from environmental samples such as soil and wood. Although phylogenetic analysis of these novel lineages is a key component of unveiling the structure and diversity of complex communities, such analyses are rare for environmental ITS data due to the difficulties of aligning this locus across significantly divergent taxa. One potential approach to this issue is simultaneous alignment and tree estimation. We targeted divergent ITS sequences of the earth tongue fungi (Geoglossomycetes), a basal class in the Ascomycota, to assess the performance of SATé, recent software that combines progressive alignment and tree building. We found that SATé performed well in generating high-quality alignments and in accurately estimating the phylogeny of earth tongue fungi. Drawing from a data set of 300 sequences of earth tongues and progressively more distant fungal lineages, 30 insufficiently identified ITS sequences from the public sequence databases were assigned to the Geoglossomycetes. The association between earth tongues and plants has been hypothesized for a long time, but hard evidence is yet to be collected. The ITS phylogeny showed that four ectomycorrhizal isolates shared a clade with Geoglossum but not with Trichoglossum earth tongues, pointing to the significant potential inherent to ecological data mining of environmental samples. Environmental sampling holds the key to many focal questions in mycology, and simultaneous alignment and tree estimation, as performed by SATé, can be a highly efficient companion in that pursuit.
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