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Open Access Publications from the University of California

Scholarly Works (9 results)

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Multicampus Research Programs and Initiatives (MRPI) Funded Publications (2018)

Coccidioides immitis and C. posadasii are primary pathogenic fungi that cause disease in immunologically-normal animals and people. The organism is found exclusively in arid regions of the Southwestern United States, Mexico, and South America, but not in other parts of the world. This study is a detailed analysis of the transposable elements (TE) in Coccidioides spp. As is common in most fungi, Class I and Class II transposons were identified and the LTR Gypsy superfamily is the most common. The minority of Coccidioides Gypsy transposons contained regions highly homologous to polyprotein domains. Phylogenetic analysis of the integrase and reverse transcriptase sequences revealed that many, but not all, of the Gypsy reverse transcriptase and integrase domains clustered by species suggesting extensive transposition after speciation of the two Coccidiodies spp. The TEs were clustered and the distribution is enriched for the ends on contigs. Analysis of gene expression data from C. immitis found that protein-coding genes within 1 kB of hAT or Gypsy TEs were poorly expressed. The expression of C. posadasii genes within 1 kB of Gypsy TEs was also significantly lower compared to all genes but the difference in expression was smaller than C. immitis. C. posadasii orthologs of C. immitis Gyspsy-associated genes were also likely to be TE-associated. In both C. immitis and C. posadasii the TEs were preferentially associated with genes annotated with protein kinase gene ontology terms. These observations suggest that TE may play a role in influencing gene expression in Coccidioides spp. Our hope is that these bioinformatic studies of the potential TE influence on expression and evolution of Coccidioides will prompt the development of testable hypotheses to better understand the role of TEs in the biology and gene regulation of Coccidioides spp.

    Creative Commons 'BY-NC-SA' version 4.0 license
    • Article
    • Peer Reviewed
    UC Riverside Previously Published Works (2018)
      Cover page: Analysis of Transposable Elements in Coccidioides Species
      • Article
      • Peer Reviewed
      UC Riverside Previously Published Works (2018)
      Coccidioides immitis and C. posadasii are primary pathogenic fungi that cause disease in immunologically-normal animals and people. The organism is found exclusively in arid regions of the Southwestern United States, Mexico, and South America, but not in other parts of the world. This study is a detailed analysis of the transposable elements (TE) in Coccidioides spp. As is common in most fungi, Class I and Class II transposons were identified and the LTR Gypsy superfamily is the most common. The minority of Coccidioides Gypsy transposons contained regions highly homologous to polyprotein domains. Phylogenetic analysis of the integrase and reverse transcriptase sequences revealed that many, but not all, of the Gypsy reverse transcriptase and integrase domains clustered by species suggesting extensive transposition after speciation of the two Coccidiodies spp. The TEs were clustered and the distribution is enriched for the ends on contigs. Analysis of gene expression data from C. immitis found that protein-coding genes within 1 kB of hAT or Gypsy TEs were poorly expressed. The expression of C. posadasii genes within 1 kB of Gypsy TEs was also significantly lower compared to all genes but the difference in expression was smaller than C. immitis. C. posadasii orthologs of C. immitis Gyspsy-associated genes were also likely to be TE-associated. In both C. immitis and C. posadasii the TEs were preferentially associated with genes annotated with protein kinase gene ontology terms. These observations suggest that TE may play a role in influencing gene expression in Coccidioides spp. Our hope is that these bioinformatic studies of the potential TE influence on expression and evolution of Coccidioides will prompt the development of testable hypotheses to better understand the role of TEs in the biology and gene regulation of Coccidioides spp.
        Creative Commons 'BY-NC-SA' version 4.0 license
        • Article
        • Peer Reviewed
        UC Riverside Previously Published Works (2010)

        Background

        Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions. Here, we start with three human proteins, SRPX, SRPX2 and CCDC80, involved in tumor suppression and progression, which possess a conserved region of similarity. Structure and function prediction allowed the definition of P-DUDES, a phylogenetically widespread, possibly ancient protein structural domain, common to vertebrates and many bacterial species.

        Results

        We show, using bioinformatics approaches, that the P-DUDES domain, surprisingly, adopts the thioredoxin-like (Thx-like) fold. A tentative, more detailed prediction of function is made, namely, that of a 2-Cys peroxiredoxin. Incidentally, consistent overexpression of all three human P-DUDES genes in two public glioblastoma microarray gene expression datasets was discovered. This finding is discussed in the context of the tumor suppressor role that has been ascribed to P-DUDES proteins in several studies. Majority of non-redundant P-DUDES proteins are found in marine metagenome, and among the bacterial species possessing this domain a trend for a higher proportion of aquatic species is observed.

        Conclusions

        The new protein structural domain, now with a broad enzymatic function predicted, may become a drug target once its detailed molecular mechanism of action is understood in detail.
          Cover page: A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2016)
          The modification of proteins by phosphorylation occurs in all life forms and is catalyzed by a large superfamily of enzymes known as protein kinases. We recently discovered a family of secretory pathway kinases that phosphorylate extracellular proteins. One member, family with sequence similarity 20C (Fam20C), is the physiological Golgi casein kinase. While examining distantly related protein sequences, we observed low levels of identity between the spore coat protein H (CotH), and the Fam20C-related secretory pathway kinases. CotH is a component of the spore in many bacterial and eukaryotic species, and is required for efficient germination of spores in Bacillus subtilis; however, the mechanism by which CotH affects germination is unclear. Here, we show that CotH is a protein kinase. The crystal structure of CotH reveals an atypical protein kinase-like fold with a unique mode of ATP binding. Examination of the genes neighboring cotH in B. subtilis led us to identify two spore coat proteins, CotB and CotG, as CotH substrates. Furthermore, we show that CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores. Collectively, our results define a family of atypical protein kinases and reveal an unexpected role for protein phosphorylation in spore biology.
            Cover page: Phosphorylation of spore coat proteins by a family of atypical protein kinases
            • Article
            • Peer Reviewed
            UC Riverside Previously Published Works (2018)
            Phylogenomic approaches have the potential to improve confidence about the inter-relationships of species in the order Mucorales within the fungal tree of life. Rhizopus species are especially important as plant and animal pathogens and bioindustrial fermenters for food and metabolite production. A dataset of 192 orthologous genes was used to construct a phylogenetic tree of 21 Rhizopus strains, classified into four species isolated from habitats of industrial, medical and environmental importance. The phylogeny indicates that the genus Rhizopus consists of three major clades, with R. microsporus as the basal species and the sister lineage to R. stolonifer and two closely related species R. arrhizus and R. delemar A comparative analysis of the mating type locus across Rhizopus reveals that its structure is flexible even between different species in the same genus, but shows similarities between Rhizopus and other mucoralean fungi. The topology of single-gene phylogenies built for two genes involved in mating is similar to the phylogenomic tree. Comparison of the total length of the genome assemblies showed that genome size varies by as much as threefold within a species and is driven by changes in transposable element copy numbers and genome duplications.
              Creative Commons 'BY-NC-SA' version 4.0 license
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              • Peer Reviewed
              UC Berkeley Previously Published Works (2024)
              DNA N6-adenine methylation (6mA) has recently gained importance as an epigenetic modification in eukaryotes. Its function in lineages with high levels, such as early-diverging fungi (EDF), is of particular interest. Here, we investigated the biological significance and evolutionary implications of 6mA in EDF, which exhibit divergent evolutionary patterns in 6mA usage. The analysis of two Mucorales species displaying extreme 6mA usage reveals that species with high 6mA levels show symmetric methylation enriched in highly expressed genes. In contrast, species with low 6mA levels show mostly asymmetric 6mA. Interestingly, transcriptomic regulation throughout development and in response to environmental cues is associated with changes in the 6mA landscape. Furthermore, we identify an EDF-specific methyltransferase, likely originated from endosymbiotic bacteria, as responsible for asymmetric methylation, while an MTA-70 methylation complex performs symmetric methylation. The distinct phenotypes observed in the corresponding mutants reinforced the critical role of both types of 6mA in EDF.
                Cover page: Symmetric and asymmetric DNA N6-adenine methylation regulates different biological responses in Mucorales
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                • Peer Reviewed
                UC Berkeley Previously Published Works (2023)
                The first genome sequenced of a eukaryotic organism was for Saccharomyces cerevisiae, as reported in 1996, but it was more than 10 years before any of the zygomycete fungi, which are the early-diverging terrestrial fungi currently placed in the phyla Mucoromycota and Zoopagomycota, were sequenced. The genome for Rhizopus delemar was completed in 2008; currently, more than 1000 zygomycete genomes have been sequenced. Genomic data from these early-diverging terrestrial fungi revealed deep phylogenetic separation of the two major clades-primarily plant-associated saprotrophic and mycorrhizal Mucoromycota versus the primarily mycoparasitic or animal-associated parasites and commensals in the Zoopagomycota. Genomic studies provide many valuable insights into how these fungi evolved in response to the challenges of living on land, including adaptations to sensing light and gravity, development of hyphal growth, and co-existence with the first terrestrial plants. Genome sequence data have facilitated studies of genome architecture, including a history of genome duplications and horizontal gene transfer events, distribution and organization of mating type loci, rDNA genes and transposable elements, methylation processes, and genes useful for various industrial applications. Pathogenicity genes and specialized secondary metabolites have also been detected in soil saprobes and pathogenic fungi. Novel endosymbiotic bacteria and viruses have been discovered during several zygomycete genome projects. Overall, genomic information has helped to resolve a plethora of research questions, from the placement of zygomycetes on the evolutionary tree of life and in natural ecosystems, to the applied biotechnological and medical questions.
                  Cover page: Sequencing the Genomes of the First Terrestrial Fungal Lineages: What Have We Learned?Creative Commons 'BY' version 4.0 license
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                  • Peer Reviewed
                  LBL Publications (2018)
                  The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.
                    Cover page: A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)
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