Publications

@article{nokey_77,

title = {First full-genome alignment representative for the genus \textit{Pestivirus}},

author = {Sandra Triebel and Tom Eulenfeld and Nancy Ontiveros-Palacios and Blake Sweeney and Norbert Tautz and Manja Marz},

url = {https://doi.org/10.5281/zenodo.15490752},

doi = {10.1101/2025.05.22.655560},

year  = {2025},

date = {2025-05-27},

journal = {bioRxiv},

abstract = {The members of the genus Pestivirus in the family Flaviviridae comprise economically important pathogens of life stock like classical swine fever (CSFV) and bovine viral diarrhea virus (BVDV). Intense research over the last years revealed that at least 11 recognized and eight proposed pestivirus species exist. The single-stranded, positive-sense RNA genome encodes for one large polyprotein which is processed by viral and cell-derived proteases into 12 mature proteins. Besides its protein-coding function, the RNA genome also contains RNA secondary structures with critical importance for various stages of the viral life cycle. Some of those RNA secondary structures, like the internal ribosome entry site (IRES) and a 3’ stem-loop essential for genome replication, had already been studied for a few individual pestiviruses.

In this study, we provide the first genome-wide multiple sequence alignment (MSA) including all known pestivirus species (accepted and tentative). Moreover, we performed a comprehensive analysis of RNA secondary structures phylogenetically conserved across the complete genus. While showing well-described structures, like a 5’ stem-loop structure, the IRES element, and the 3’ stem loop SL I to be conserved between all pestiviruses, other RNA secondary structures in the 3’ untranslated region (UTR) were only conserved in subsets of the species. We identified 29 novel phylogenetically conserved RNA secondary structures in the protein-coding region, with so far unresolved functional importance. The microRNA binding site for miR-17 was previously known in species A, B, and C; in this study, we identified it in ten additional species, but not in species K, S, Q, and R. Another interesting finding is the identification of a putative long-distance RNA interaction between the IRES and the 3’ end of the genome. These results together with the now available comprehensive multiple sequence alignment including all 19 pestivirus species, represent a valuable resource for future research and diagnostic purposes.},

keywords = {alignment, evolution, phylogenetics, RNA structure, RNA-RNA interactions, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_76,

title = {Immunity and bacterial recruitment in plant leaves are parallel processes that together shape sensitivity to temperature stress},

author = {Jisna Jose and Erik Teutloff and Teresa Mayer and Simrat Naseem and Emanuel Barth and Rayko Halitschke and Manja Marz and Matthew T. Agler},

doi = {10.1101/2024.06.10.598336},

year  = {2025},

date = {2025-04-25},

journal = {bioRxiv},

abstract = {Rising global temperatures necessitate developing resilient crops with better adaptability to changing climates. Under elevated temperatures, plant immunity is downregulated, increasing risk of foliar pathogen attack. Manipulating plant defense hormones is one way to mitigate this detrimental effect. However, it is unclear how plant immunity interacts with plant microbiome assembly and how temperature will thus affect overall plant health and stability. In this study, we compared two Arabidopsis thaliana genotypes that feature divergent strategies for recruitment of commensal bacteria from natural soil. NG2, an A. thaliana ecotype we collected from Jena, Germany, was grown in its native soil and compared to CLLF, a genotype that recruits higher bacterial loads and higher bacterial diversity but without any dysbiotic phenotype. CLLF hyperaccumulates salicylic acid (SA) and jasmonates, has constitutively upregulated innate defenses, and shows increased resistance to necrotrophic fungal and hemi-biotrophic bacterial pathogens, indicating that pathogen immunity and non-pathogen recruitment function in parallel. Some of its leaf bacteria can utlize SA as a carbon source, suggesting that immunity and recruitment may even be linked by chemical hormones. CLLF exhibits high tolerance to heat stress in comparison to the NG2, with SA-associated defense processes remaining active under heat. Synthetic community (SynCom) experiments revealed that when the taxonomic diversity of bacteria available to CLLF is artificially reduced, resilience to heat stress is compromised, leading to dysbiosis. However, this dysbiosis does not occur in CLLF with a full SynCom or in the NG2 with any SynCom. These findings suggest that the downregulation of defenses in response to heat may contribute to the avoidance of dysbiosis caused by certain leaf bacteria, while full bacteriome taxonomic diversity can help maintain balance.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {bacteria, evolution, fungi, metagenomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_80,

title = {Exploring the genomic landscape of Chlamydiifrater species: novel features include multiple truncated major outer membrane proteins, unique genes and chlamydial plasticity zone orthologs},

author = {Martin Hölzer and Charlotte Reuschel and Fabien Vorimore and Karine Laroucau and Konrad Sachse},

doi = {10.1099/acmi.0.000936.v3},

year  = {2025},

date = {2025-02-03},

urldate = {2025-02-03},

journal = {Access Microbiology},

volume = {7},

abstract = {Recently discovered obligate intracellular bacteria belonging to the genus Chlamydiifrater with the species of Chlamydiifrater phoenicopteri and Chlamydiifrater volucris were studied to explore the composition of their genomes and their relatedness to Chlamydia, the other genus of the family Chlamydiaceae. We investigated 4 isolates of Cf. volucris, 2 of them newly sequenced, and one of Cf. phoenicopteri alongside 12 representatives of the Chlamydia species. Our study uncovers previously unrecognized genomic structures within Chlamydiifrater using a hybrid sequencing approach and advanced annotation pipelines, providing insights into species-specific adaptations and evolutionary dynamics. The integration of long-read sequencing data, comprehensive re-annotation strategies and pan-genomics enabled the localization of the unique plasticity zone and the identification of novel gene clusters in Chlamydiifrater strains, which improves our understanding of chlamydial genome architecture and plasticity in the family Chlamydiaceae. Our analysis revealed that 761 CDS (~80%) are shared among members of both genera. We further identified 158 unique genes of Chlamydiifrater species, but their annotation remains challenging because of the absence of functionally annotated orthologs in public databases. A full-length ompA gene encoding the major outer membrane porin was seen in all Chlamydiifrater strains. We also describe the localization and structure of multiple truncated CDS of ompA family members, representing one of this study’s most interesting findings. While genome analysis of Chlamydiifrater spp. confirmed numerous common features shared with representatives of the genus Chlamydia, many unique genomic elements were identified that underpin the distinct phenotype and separate genetic position of these new microorganisms.},

keywords = {annotation, bacteria, DNA / genomics, evolution, pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_66,

title = {Endogenous viral elements: insights into data availability and accessibility},

author = {Muriel Ritsch and Nadja Brait and Erin Harvey and Manja Marz and Sebastian Lequime},

doi = {10.1093/ve/veae099},

issn = {2057-1577},

year  = {2024},

date = {2024-11-23},

journal = {Virus Evolution},

volume = {10},

number = {1},

pages = {veae099},

abstract = {Endogenous viral elements (EVEs) are remnants of viral genetic material endogenized into the host genome. They have, in the last decades, attracted attention for their role as potential contributors to pathogenesis, drivers of selective advantage for the host, and genomic remnants of ancient viruses. EVEs have a nuanced and complex influence on both host health and evolution, and can offer insights on the deep evolutionary history of viruses. As an emerging field of research, several factors limit a comprehensive understanding of EVEs: they are currently underestimated and periodically overlooked in studies of the host genome, transcriptome, and virome. The absence of standardized guidelines for ensuring EVE-related data availability and accessibility following the FAIR (‘findable, accessible, interoperable, and reusable’) principles obstructs our ability to gather and connect information. Here, we discuss challenges to the availability and accessibility of EVE-related data and propose potential solutions. We identified the biological and research focus imbalance between different types of EVEs, and their overall biological complexity as genomic loci with viral ancestry, as potential challenges that can be addressed with the development of a user-oriented identification tool. In addition, reports of EVE identification are scattered between different subfields under different keywords, and EVE sequences and associated data are not properly gathered in databases. While developing an open and dedicated database might be ideal, targeted improvements of generalist databases might provide a pragmatic solution to EVE data and metadata accessibility. The implementation of these solutions, as well as the collective effort by the EVE scientific community in discussing and setting guidelines, is now drastically needed to lead the development of EVE research and offer insights into host–virus interactions and their evolutionary history.},

keywords = {evolution, phylogenetics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_66,

title = {Endogenous Bornavirus-like Elements in Bats: Evolutionary Insights from the Conserved Riboviral L-Gene in Microbats and Its Antisense Transcription in \textit{Myotis daubentonii}},

author = {Muriel Ritsch and Tom Eulenfeld and Kevin Lamkiewicz and Andreas Schoen and Friedemann Weber and Martin Hölzer and Manja Marz},

doi = {10.3390/v16081210},

issn = {1999-4915},

year  = {2024},

date = {2024-07-27},

urldate = {2024-07-27},

journal = {Viruses},

volume = {16},

issue = {8},

abstract = {Bats are ecologically diverse vertebrates characterized by their ability to host a wide range of viruses without apparent illness and the presence of numerous endogenous viral elements (EVEs). EVEs are well preserved, expressed, and may affect host biology and immunity, but their role in bat immune system evolution remains unclear. Among EVEs, endogenous bornavirus-like elements (EBLs) are bornavirus sequences integrated into animal genomes. Here, we identified a novel EBL in the microbat \textit{Myotis daubentonii}, EBLL-Cultervirus.10-MyoDau (short name is CV.10-MyoDau) that shows protein-level conservation with the L-protein of a \textit{Cultervirus} (Wuhan sharpbelly bornavirus). Surprisingly, we discovered a transcript on the antisense strand comprising three exons, which we named AMCR-MyoDau. The active transcription in \textit{Myotis daubentonii} tissues of AMCR-MyoDau, confirmed by RNA-Seq analysis and RT-PCR, highlights its potential role during viral infections. Using comparative genomics comprising 63 bat genomes, we demonstrate nucleotide-level conservation of CV.10-MyoDau and AMCR-MyoDau across various bat species and its detection in 22 \textit{Yangochiropera<i/> and 12 \textit{Yinpterochiroptera} species. To the best of our knowledge, this marks the first occurrence of a conserved EVE shared among diverse bat species, which is accompanied by a conserved antisense transcript. This highlights the need for future research to explore the role of EVEs in shaping the evolution of bat immunity.},

keywords = {evolution, phylogenetics, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_62,

title = {Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus},

author = {Sandra Triebel and Kevin Lamkiewicz and Nancy Ontiveros and Blake Sweeney and Peter F. Stadler and Anton I. Petrov and Michael Niepmann and Manja Marz},

doi = {10.1038/s41598-024-62897-0},

year  = {2024},

date = {2024-07-02},

urldate = {2024-07-02},

journal = {Scientific Reports},

volume = {14},

issue = {1},

abstract = {Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large ‘cloud’ of RNA genomes (quasispecies) which—by trial and error—comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.},

keywords = {evolution, ncRNAs, phylogenetics, RNA structure, RNA-RNA interactions, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_63,

title = {RIBAP: a comprehensive bacterial core genome annotation pipeline for pangenome calculation beyond the species level},

author = {Kevin Lamkiewicz and Lisa-Marie Barf and Konrad Sachse and Martin Hölzer},

doi = {10.1186/s13059-024-03312-9},

year  = {2024},

date = {2024-07-01},

journal = {Genome Biology},

volume = {25},

issue = {1},

abstract = {Microbial pangenome analysis identifies present or absent genes in prokaryotic genomes. However, current tools are limited when analyzing species with higher sequence diversity or higher taxonomic orders such as genera or families. The Roary ILP Bacterial core Annotation Pipeline (RIBAP) uses an integer linear programming approach to refine gene clusters predicted by Roary for identifying core genes. RIBAP successfully handles the complexity and diversity of Chlamydia, Klebsiella, Brucella, and Enterococcus genomes, outperforming other established and recent pangenome tools for identifying all-encompassing core genes at the genus level. RIBAP is a freely available Nextflow pipeline at github.com/hoelzer-lab/ribap and zenodo.org/doi/10.5281/zenodo.10890871.},

keywords = {annotation, bacteria, DNA / genomics, evolution, software},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Immunity and bacterial recruitment in plant leaves are parallel processes whose link shapes sensitivity to temperature stress},

author = {Jisna Jose and Erik Teutloff and Simrat Naseem and Emanuel Barth and Rayko Halitschke and Manja Marz and Matthew T. Agler},

doi = {10.1101/2024.06.10.598336},

year  = {2024},

date = {2024-06-10},

journal = {bioRxiv},

abstract = {Rising global temperatures necessitate developing climate-resilient crops with better adaptability to changing climates. Under elevated temperatures, plant immunity is downregulated, putting them at risk of foliar pathogen attack. Manipulating plant defense hormones is one way to mitigate this detrimental effect. However, it is unclear how plant immunity interacts with plant microbiome assembly and how temperature will thus affect overall plant health and stability. We used chemical mutagenesis to identify a phenotypically healthy genotype of A. thaliana, “CLLF”, that compared to the wild type naturally recruits an altered leaf bacteriome, including unusually high bacteria loads. Simultaneously, CLLF hyperaccumulates salicylic acid (SA) and jasmonates, has constitutively upregulated systemic and innate defenses, and has increased resistance to necrotrophic fungal and hemi-biotrophic bacterial pathogens, indicating that pathogen immunity and non-pathogen recruitment function in parallel. Growth of specific non-pathogenic leaf bacteria on SA as a carbon source suggests the same hormones may even link the two processes. CLLF also showed high tolerance to heat stress in comparison to the wild type, but SA-associated defense processes are not downregulated under heat. Synthetic community (SynCom) experiments showed that when the taxonomic diversity of bacteria available to CLLF is artificially reduced, resilience to heat stress is compromised, leading to dysbiosis, but this does not occur with the full SynCom or in the wild type with any SynCom. Thus, the downregulation of defenses in response to heat may contribute to avoidance of dysbiosis caused by some leaf bacteria, but full bacteriome taxonomic diversity can restore balance.



Significance Statement Plants are living ecosystems colonized by diverse microorganisms who strongly shape host health. Understanding how balance arises in host-associated microbiomes is a key step to understanding how to preserve, manage and possibly optimize these complex ecosystems, especially in a changing climate. Using a random mutagenesis approach in a natural A. thaliana ecotype, we find that constitutively upregulated defenses are associated with both tolerance to (a)biotic threats and healthy recruitment of leaf bacteria, very likely in a direct manner. Thus, immunity and bacterial recruitment in leaves operate in parallel. Synthetic community experiments show further that this link plays important roles in shaping plant resilience to heat stress, an important consideration in developing plants more stable to climate change.},

keywords = {bacteria, evolution, fungi, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Genome Structure, Life Cycle, and Taxonomy of Coronaviruses and the Evolution of SARS-CoV-2},

author = {Kevin Lamkiewicz and Luis Roger Esquivel Gomez and Denise Kühnert and Manja Marz

},

doi = {10.1007/978-3-031-15640-3_9},

year  = {2023},

date = {2023-01-03},

journal = {Curr Top Microbiol Immunol},

volume = {439},

pages = {305-339},

abstract = {Coronaviruses have a broad host range and exhibit high zoonotic potential. In this chapter, we describe their genomic organization in terms of encoded proteins and provide an introduction to the peculiar discontinuous transcription mechanism. Further, we present evolutionary conserved genomic RNA secondary structure features, which are involved in the complex replication mechanism. With a focus on computational methods, we review the emergence of SARS-CoV-2 starting with the 2019 strains. In that context, we also discuss the debated hypothesis of whether SARS-CoV-2 was created in a laboratory. We focus on the molecular evolution and the epidemiological dynamics of this recently emerged pathogen and we explain how variants of concern are detected and characterised. COVID-19, the disease caused by SARS-CoV-2, can spread through different transmission routes and also depends on a number of risk factors. We describe how current computational models of viral epidemiology, or more specifically, phylodynamics, have facilitated and will continue to enable a better understanding of the epidemic dynamics of SARS-CoV-2.},

keywords = {coronavirus, DNA / genomics, evolution, phylogenetics, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_96,

title = {Characterisation and Molecular Analysis of an Unusual Chimeric Methicillin Resistant Staphylococcus Aureus Strain and its Bacteriophages},

author = {Sindy Burgold-Voigt and Stefan Monecke and Alexandra Simbeck and Thomas Holzmann and Bärbel Kieninger and Elisabeth M. Liebler-Tenorio and Sascha D. Braun and Maximilian Collatz and Celia Diezel and Elke Müller and Wulf Schneider-Brachert and Ralf Ehricht},

doi = {10.3389/fgene.2021.723958},

year  = {2021},

date = {2021-11-18},

journal = {Frontiers in Genetics},

volume = {12},

abstract = {In the context of microarray-based epidemiological typing of the clonal organism Staphylococcus aureus/MRSA, a strain was identified that did not belong to known clonal complexes. The molecular analysis by microarray-based typing yielded signals suggesting that it was a mosaic or hybrid strain of two lineages. To verify this result, the isolate was sequenced with both, short-read Illumina and long-read Nanopore technologies and analysed in detail. This supported the hypothesis that the genome of this strain, ST6610-MRSA-IVg comprised of segments originating from two different clonal complexes (CC).

While the backbone of the strain´s genome, i.e., roughly 2 megabases, belongs to CC8, a continuous insert of 894 kb (approx. 30% of the genome) originated from CC140. Beside core genomic markers in the normal succession and orientation, this insert also included the mecA gene, coding for PbP2a and causing methicillin resistance , localised on an SCCmec IVg element. This particular SCCmec type was also previously observed in CC140 MRSA from African countries. A second conspicuous observation was the presence of the trimethoprim resistance gene dfrG within on a prophage that occupied an attachment site normally used by Panton-Valentine Leucocidin (PVL) phages. 

This observation could indicate a role of large-scale chromosomal recombination in the evolution of S. aureus as well as a role of phages in the dissemination of antibiotic resistance genes.},

keywords = {bacteria, DNA / genomics, evolution},

pubstate = {published},

tppubtype = {article}

}

@article{Walker:21,

title = {Characterization of SARS-CoV-2 infection clusters based on integrated genomic surveillance, outbreak analysis and contact tracing in an urban setting},

author = {Andreas Walker and Torsten Houwaart and Patrick Finzer and Lutz Ehlkes and Alona Tyshaieva and Maximilian Damagnez and Daniel Strelow and Ashley Duplessis and Jessica Nicolai and Tobias Wienemann and Teresa Tamayo and Malte Kohns Vasconcelos and Lisanna Hülse and Katrin Hoffmann and Nadine Lübke and Sandra Hauka and Marcel Andree and Martin P Däumer and Alexander Thielen and Susanne Kolbe-Busch and Klaus Göbels and Rainer Zotz and Klaus Pfeffer and Jörg Timm and Alexander T Dilthey and Deutsche COVID-19 OMICS Initiative (DeCOI)},

doi = {10.1093/cid/ciab588},

year  = {2021},

date = {2021-06-28},

urldate = {2021-06-28},

journal = {Clin Infect Dis},

pages = {ciab588},

publisher = {Oxford University Press (OUP)},

abstract = {Background: Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing.



Methods: In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform.



Results: Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population.



Conclusions: Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population.},

keywords = {coronavirus, evolution, nanopore, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Yates:21,

title = {The evolution and changing ecology of the African hominid oral microbiome},

author = {James A. Fellows Yates and Irina M. Velsko and Franziska Aron and Cosimo Posth and Courtney A. Hofman and Rita M. Austin and Cody E. Parker and Allison E. Mann and Kathrin Nägele and Kathryn Weedman Arthur and John W. Arthur and Catherine C. Bauer and Isabelle Crevecoeur and Christophe Cupillard and Matthew C. Curtis and Love Dalén and Marta Díaz-Zorita Bonilla and J. Carlos Díez Fernández-Lomana and Dorothée G. Drucker and Elena Escribano Escrivá and Michael Francken and Victoria E. Gibbon and Manuel R. González Morales and Ana Grande Mateu and Katerina Harvati and Amanda G. Henry and Louise Humphrey and Mario Menéndez and Dušan Mihailović and Marco Peresani and Sofía Rodríguez Moroder and Mirjana Roksandic and Hélène Rougier and Sandra Sázelová and Jay T. Stock and Lawrence Guy Straus and Jiří Svoboda and Barbara Teßmann and Michael J. Walker and Robert C. Power and Cecil M. Lewis and Krithivasan Sankaranarayanan and Katerina Guschanski and Richard W. Wrangham and Floyd E. Dewhirst and Domingo C. Salazar-García and Johannes Krause and Alexander Herbig and Christina Warinner},

doi = {10.1073/pnas.2021655118},

year  = {2021},

date = {2021-05-18},

urldate = {2021-05-18},

journal = {Proc Natl Acad Sci},

volume = {118},

number = {20},

pages = {e2021655118},

publisher = {Proceedings of the National Academy of Sciences},

abstract = {The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine–platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.},

keywords = {ancient DNA, bacteria, evolution, phylogenetics},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky:20b,

title = {The International Virus Bioinformatics Meeting 2020},

author = {Franziska Hufsky and Niko Beerenwinkel and Irmtraud M. Meyer and Simon Roux and Georgia May Cook and Cormac M. Kinsella and Kevin Lamkiewicz and Mike Marquet and David F. Nieuwenhuijse and Ingrida Olendraite and Sofia Paraskevopoulou and Francesca Young and Ronald Dijkman and Bashar Ibrahim and Jenna Kelly and Philippe Le Mercier and Manja Marz and Alban Ramette and Volker Thiel},

doi = {10.3390/v12121398},

year  = {2020},

date = {2020-12-06},

urldate = {2020-01-01},

journal = {Viruses},

volume = {12},

number = {12},

pages = {1398},

publisher = {MDPI AG},

abstract = {The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, in March 2020. However, the COVID-19 pandemic put a spoke in the wheel of almost all conferences to be held in 2020. After moving the conference to 8–9 October 2020, we got hit by the second wave and finally decided at short notice to go fully online. On the other hand, the pandemic has made us even more aware of the importance of accelerating research in viral bioinformatics. Advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks. The International Virus Bioinformatics Meeting 2020 has attracted approximately 120 experts in virology and bioinformatics from all over the world to join the two-day virtual meeting. Despite concerns being raised that virtual meetings lack possibilities for face-to-face discussion, the participants from this small community created a highly interactive scientific environment, engaging in lively and inspiring discussions and suggesting new research directions and questions. The meeting featured five invited and twelve contributed talks, on the four main topics: (1) proteome and RNAome of RNA viruses, (2) viral metagenomics and ecology, (3) virus evolution and classification and (4) viral infections and immunology. Further, the meeting featured 20 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.},

keywords = {classification, conference report, evolution, metagenomics, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky:20a,

title = {Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research},

author = {Franziska Hufsky and Kevin Lamkiewicz and Alexandre Almeida and Abdel Aouacheria and Cecilia Arighi and Alex Bateman and Jan Baumbach and Niko Beerenwinkel and Christian Brandt and Marco Cacciabue and Sara Chuguransky and Oliver Drechsel and Robert D Finn and Adrian Fritz and Stephan Fuchs and Georges Hattab and Anne-Christin Hauschild and Dominik Heider and Marie Hoffmann and Martin Hölzer and Stefan Hoops and Lars Kaderali and Ioanna Kalvari and Max Kleist and Renó Kmiecinski and Denise Kühnert and Gorka Lasso and Pieter Libin and Markus List and Hannah F Löchel and Maria J Martin and Roman Martin and Julian Matschinske and Alice C McHardy and Pedro Mendes and Jaina Mistry and Vincent Navratil and Eric P Nawrocki and Áine Niamh O'Toole and Nancy Ontiveros-Palacios and Anton I Petrov and Guillermo Rangel-Pineros and Nicole Redaschi and Susanne Reimering and Knut Reinert and Alejandro Reyes and Lorna Richardson and David L Robertson and Sepideh Sadegh and Joshua B Singer and Kristof Theys and Chris Upton and Marius Welzel and Lowri Williams and Manja Marz},

url = {http://evbc.uni-jena.de/tools/coronavirus-tools/},

doi = {10.1093/bib/bbaa232},

year  = {2020},

date = {2020-11-04},

urldate = {2020-11-04},

journal = {Brief Bioinform},

volume = {22},

number = {2},

pages = {642--663},

publisher = {Oxford University Press (OUP)},

abstract = {SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories.},

keywords = {coronavirus, evolution, review, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hoelzer:20a,

title = {PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection},

author = {Martin Hölzer and Manja Marz},

editor = {Alfonso Valencia},

url = {https://github.com/rnajena/poseidon},

doi = {10.1093/bioinformatics/btaa695},

year  = {2020},

date = {2020-07-31},

urldate = {2020-07-31},

journal = {Bioinformatics},

volume = {37},

number = {7},

pages = {1018-1020},

publisher = {Oxford University Press (OUP)},

abstract = {PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. By entering homologous sequences, PoSeiDon builds an alignment, estimates a best-fitting substitution model and performs a recombination analysis followed by the construction of all corresponding phylogenies. Finally, significantly positive selected sites are detected according to different models for the full alignment and possible recombination fragments. The results of PoSeiDon are summarized in a user-friendly HTML page providing all intermediate results and the graphical representation of recombination events and positively selected sites.



},

keywords = {alignment, evolution, phylogenetics, software},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky:20,

title = {Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research},

author = {Franziska Hufsky and Kevin Lamkiewicz and Alexandre Almeida and Abdel Aouacheria and Cecilia Arighi and Alex Bateman and Jan Baumbach and Niko Beerenwinkel and Christian Brandt and Marco Cacciabue and Sara Chuguransky and Oliver Drechsel and Robert D. Finn and Adrian Fritz and Stephan Fuchs and Georges Hattab and Anne-Christin Hauschild and Dominik Heider and Marie Hoffmann and Martin Hölzer and Stefan Hoops and Lars Kaderali and Ioanna Kalvari and Max Kleist and Rene Kmiecinski and Denise Kühnert and Gorka Lasso and Pieter Libin and Markus List and Hannah F. Löchel and Maria J. Martin and Roman Martin and Julian Matschinske and Alice C. McHardy and Pedro Mendes and Jaina Mistry and Vincent Navratil and Eric Nawrocki and Áine Niamh O'Toole and Nancy Palacios-Ontiveros and Anton I. Petrov and Guillermo Rangel-Piñeros and Nicole Redaschi and Susanne Reimering and Knut Reinert and Alejandro Reyes and Lorna Richardson and David L. Robertson and Sepideh Sadegh and Joshua B. Singer and Kristof Theys and Chris Upton and Marius Welzel and Lowri Williams and Manja Marz},

doi = {10.20944/preprints202005.0376.v1},

year  = {2020},

date = {2020-05-23},

urldate = {2020-05-23},

journal = {Preprints},

publisher = {MDPI AG},

abstract = {SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding, and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are freely available online, either through web applications or public code repositories.

},

note = {Now published in Brief Bioinform: https://dx.doi.org/10.1093/bib/bbaa232},

keywords = {coronavirus, evolution, review, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Mostajo:20,

title = {A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes},

author = {Nelly F. Mostajo and Marie Lataretu and Sebastian Krautwurst and Florian Mock and Daniel Desirò and Kevin Lamkiewicz and Maximilian Collatz and Andreas Schoen and Friedemann Weber and Manja Marz and Martin Hölzer},

url = {https://www.rna.uni-jena.de/supplements/bats/index.html},

doi = {10.1093/nargab/lqz006},

year  = {2019},

date = {2019-09-30},

urldate = {2019-09-30},

journal = {NAR Genomics Bioinf},

volume = {2},

number = {1},

pages = {lqz006},

abstract = {Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.},

keywords = {annotation, assembly, differential expression analysis, evolution, ncRNAs, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hufsky:19,

title = {The Third Annual Meeting of the European Virus Bioinformatics Center},

author = {Franziska Hufsky and Bashar Ibrahim and Sejal Modha and Martha R. J. Clokie and Stefanie Deinhardt-Emmer and Bas E. Dutilh and Samantha Lycett and Peter Simmonds and Volker Thiel and Aare Abroi and Evelien M. Adriaenssens and Marina Escalera-Zamudio and Jenna Nicole Kelly and Kevin Lamkiewicz and Lu Lu and Julian Susat and Thomas Sicheritz and David L. Robertson and Manja Marz},

doi = {10.3390/v11050420},

year  = {2019},

date = {2019-05-05},

urldate = {2019-05-05},

journal = {Viruses},

volume = {11},

number = {5},

pages = {420},

publisher = {MDPI AG},

abstract = {The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting. },

keywords = {classification, conference report, evolution, metagenomics, software, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Fricke:18,

title = {Global importance of RNA secondary structures in protein coding sequences},

author = {Markus Fricke and Ruman Gerst and Bashar Ibrahim and Michael Niepmann and Manja Marz},

doi = {10.1093/bioinformatics/bty678},

year  = {2018},

date = {2018-08-07},

urldate = {2018-08-07},

journal = {Bioinformatics},

volume = {35},

number = {4},

pages = {579–583},

abstract = {The protein-coding sequences of messenger RNAs are the linear template for translation of the gene sequence into protein. Nevertheless, the RNA can also form secondary structures by intramolecular base-pairing. We show that the nucleotide distribution within codons is biased in all taxa of life on a global scale. Thereby, RNA secondary structures that require base-pairing between the position 1 of a codon with the position 1 of an opposing codon (here named RNA secondary structure class c1) are under-represented. We conclude that this bias may result from the co-evolution of codon sequence and mRNA secondary structure, suggesting that RNA secondary structures are generally important in protein coding regions of mRNAs. The above result also implies that codon position 2 has a smaller influence on the amino acid choice than codon position 1.},

keywords = {evolution, RNA / transcriptomics, RNA structure, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Ibrahim:18,

title = {Bioinformatics Meets Virology: The European Virus Bioinformatics Center's Second Annual Meeting},

author = {Bashar Ibrahim and Ksenia Arkhipova and Arno C. Andeweg and Susana Posada-Céspedes and François Enault and Arthur Gruber and Eugene V. Koonin and Anne Kupczok and Philippe Lemey and Alice C. McHardy and Dino P. McMahon and Brett E. Pickett and David L. Robertson and Richard H. Scheuermann and Alexandra Zhernakova and Mark P. Zwart and Alexander Schönhuth and Bas E. Dutilh and Manja Marz},

doi = {10.3390/v10050256},

year  = {2018},

date = {2018-05-14},

urldate = {2018-05-14},

journal = {Viruses},

volume = {10},

abstract = {The Second Annual Meeting of the European Virus Bioinformatics Center (EVBC), held in Utrecht, Netherlands, focused on computational approaches in virology, with topics including (but not limited to) virus discovery, diagnostics, (meta-)genomics, modeling, epidemiology, molecular structure, evolution, and viral ecology. The goals of the Second Annual Meeting were threefold: (i) to bring together virologists and bioinformaticians from across the academic, industrial, professional, and training sectors to share best practice; (ii) to provide a meaningful and interactive scientific environment to promote discussion and collaboration between students, postdoctoral fellows, and both new and established investigators; (iii) to inspire and suggest new research directions and questions. Approximately 120 researchers from around the world attended the Second Annual Meeting of the EVBC this year, including 15 renowned international speakers. This report presents an overview of new developments and novel research findings that emerged during the meeting.},

keywords = {conference report, evolution, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Hillmann:18,

title = {Multiple Roots of Fruiting Body Formation in Amoebozoa},

author = {Falk Hillmann and Gillian Forbes and Silvia Novohradská and Iuliia Ferling and Konstantin Riege and Marco Groth and Martin Westermann and Manja Marz and Thomas Spaller and Thomas Winckler and Pauline Schaap and Gernot Glöckner},

doi = {10.1093/gbe/evy011},

year  = {2018},

date = {2018-01-25},

urldate = {2018-01-25},

journal = {Genome Biol Evol},

volume = {10},

pages = {591--606},

abstract = {Establishment of multicellularity represents a major transition in eukaryote evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively simple aggregative multicellular stage resulting in a fruiting body supported by a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree, differ by producing only one or few single stalked spores. Thus, one obvious difference in the developmental cycle of protosteliids and dictyosteliids seems to be the establishment of multicellularity. To separate spore development from multicellular interactions, we compared the genome and transcriptome of a Protostelium species (Protostelium aurantium var. fungivorum) with those of social and solitary members of the Amoebozoa. During fruiting body formation nearly 4,000 genes, corresponding to specific pathways required for differentiation processes, are upregulated. A comparison with genes involved in the development of dictyosteliids revealed conservation of >500 genes, but most of them are also present in Acanthamoeba castellanii for which fruiting bodies have not been documented. Moreover, expression regulation of those genes differs between P. aurantium and Dictyostelium discoideum. Within Amoebozoa differentiation to fruiting bodies is common, but our current genome analysis suggests that protosteliids and dictyosteliids used different routes to achieve this. Most remarkable is both the large repertoire and diversity between species in genes that mediate environmental sensing and signal processing. This likely reflects an immense adaptability of the single cell stage to varying environmental conditions. We surmise that this signaling repertoire provided sufficient building blocks to accommodate the relatively simple demands for cell-cell communication in the early multicellular forms.},

keywords = {evolution, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Hoelzer:17,

title = {Software Dedicated to Virus Sequence Analysis },

author = {Martin Hölzer and Manja Marz},

doi = {10.1016/bs.aivir.2017.08.004},

year  = {2017},

date = {2017-09-28},

urldate = {2017-09-28},

journal = {Adv Virus Res},

volume = {99},

pages = {233--257},

abstract = {Computer-assisted technologies of the genomic structure, biological function, and evolution of viruses remain a largely neglected area of research. The attention of bioinformaticians to this challenging field is currently unsatisfying in respect to its medical and biological importance. The power of new genome sequencing technologies, associated with new tools to handle "big data", provides unprecedented opportunities to address fundamental questions in virology. Here, we present an overview of the current technologies, challenges, and advantages of Next-Generation Sequencing (NGS) in relation to the field of virology. We present how viral sequences can be detected de novo out of current short-read NGS data. Furthermore, we discuss the challenges and applications of viral quasispecies and how secondary structures, commonly shaped by RNA viruses, can be computationally predicted. The phylogenetic analysis of viruses, as another ubiquitous field in virology, forms an essential element of describing viral epidemics and challenges current algorithms. Recently, the first specialized virus-bioinformatic organizations have been established. We need to bring together virologists and bioinformaticians and provide a platform for the implementation of interdisciplinary collaborative projects at local and international scales. Above all, there is an urgent need for dedicated software tools to tackle various challenges in virology.},

keywords = {DNA / genomics, evolution, phylogenetics, review, RNA / transcriptomics, RNA structure, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Fuchs:17,

title = {Evolution and Antiviral Specificities of Interferon-Induced Mx Proteins of Bats against Ebola, Influenza, and Other RNA Viruses},

author = {Jonas Fuchs and Martin Hölzer and Mirjam Schilling and Corinna Patzina and Andreas Schoen and Thomas Hoenen and Gert Zimmer and Manja Marz and Friedemann Weber and Marcel A Müller and Georg Kochs},

doi = {10.1128/JVI.00361-17},

year  = {2017},

date = {2017-07-12},

urldate = {2017-07-12},

journal = {J Virol},

volume = {91},

abstract = {Bats serve as a reservoir for various, often zoonotic viruses, including significant human pathogens such as Ebola and influenza viruses. However, for unknown reasons, viral infections rarely cause clinical symptoms in bats. A tight control of viral replication by the host innate immune defense might contribute to this phenomenon. Transcriptomic studies revealed the presence of the interferon-induced antiviral myxovirus resistance (Mx) proteins in bats, but detailed functional aspects have not been assessed. To provide evidence that bat Mx proteins might act as key factors to control viral replication we cloned cDNAs from three bat families, Pteropodidae, Phyllostomidae, and Vespertilionidae. Phylogenetically these bat genes cluster closely with their human ortholog MxA. Using transfected cell cultures, minireplicon systems, virus-like particles, and virus infections, we determined the antiviral potential of the bat Mx1 proteins. Bat Mx1 significantly reduced the polymerase activity of viruses circulating in bats, including Ebola and influenza A-like viruses. The related Thogoto virus, however, which is not known to infect bats, was not inhibited by bat Mx1. Further, we provide evidence for positive selection in bat genes that might explain species-specific antiviral activities of these proteins. Together, our data suggest a role for Mx1 in controlling these viruses in their bat hosts. Bats are a natural reservoir for various viruses that rarely cause clinical symptoms in bats but are dangerous zoonotic pathogens, like Ebola or rabies virus. It has been hypothesized that the interferon system might play a key role in controlling viral replication in bats. We speculate that the interferon-induced Mx proteins might be key antiviral factors of bats and have coevolved with bat-borne viruses. This study evaluated for the first time a large set of bat Mx1 proteins spanning three major bat families for their antiviral potential, including activity against Ebola virus and bat influenza A-like virus, and we describe here their phylogenetic relationship, revealing patterns of positive selection that suggest a coevolution with viral pathogens. By understanding the molecular mechanisms of the innate resistance of bats against viral diseases, we might gain important insights into how to prevent and fight human zoonotic infections caused by bat-borne viruses.},

keywords = {evolution, phylogenetics, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Winter:16,

title = {Finding approximate gene clusters with Gecko 3},

author = {Sascha Winter and Katharina Jahn and Stefanie Wehner and Leon Kuchenbecker and Manja Marz and Jens Stoye and Sebastian Böcker},

url = {http://bio.informatik.uni-jena.de/software/gecko3/},

doi = {10.1093/nar/gkw843},

year  = {2016},

date = {2016-09-26},

urldate = {2016-09-26},

journal = {Nucleic Acids Res},

volume = {44},

pages = {9600--9610},

abstract = {Gene-order-based comparison of multiple genomes provides signals for functional analysis of genes and the evolutionary process of genome organization. Gene clusters are regions of co-localized genes on genomes of different species. The rapid increase in sequenced genomes necessitates bioinformatics tools for finding gene clusters in hundreds of genomes. Existing tools are often restricted to few (in many cases, only two) genomes, and often make restrictive assumptions such as short perfect conservation, conserved gene order or monophyletic gene clusters. We present Gecko 3, an open-source software for finding gene clusters in hundreds of bacterial genomes, that comes with an easy-to-use graphical user interface. The underlying gene cluster model is intuitive, can cope with low degrees of conservation as well as misannotations and is complemented by a sound statistical evaluation. To evaluate the biological benefit of Gecko 3 and to exemplify our method, we search for gene clusters in a dataset of 678 bacterial genomes using Synechocystis sp. PCC 6803 as a reference. We confirm detected gene clusters reviewing the literature and comparing them to a database of operons; we detect two novel clusters, which were confirmed by publicly available experimental RNA-Seq data. The computational analysis is carried out on a laptop computer in <40 min.},

keywords = {bacteria, DNA / genomics, evolution, software},

pubstate = {published},

tppubtype = {article}

}

@article{Barth:16,

title = {The Evolution of COP9 Signalosome in Unicellular and Multicellular Organisms},

author = {Emanuel Barth and Ron Hübler and Aria Baniahmad and Manja Marz},

doi = {10.1093/gbe/evw073},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Genome Biol Evol},

volume = {8},

number = {4},

pages = {1279--1289},

abstract = {The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5. This may indicate a strong evolutionary selection for these two subunits. Despite the strong conservation of the protein sequence, the genomic structures of the intron/exon boundaries indicate no conservation at genomic level. This suggests that the gene structure is exposed to a much less selection compared with the protein sequence. We also show the conservation of important active domains, such as PCI (proteasome lid-CSN-initiation factor) and MPN (MPR1/PAD1 amino-terminal). We identified novel exons and alternative splicing variants for all CSN subunits. This indicates another level of complexity of the CSN. Notably, most COP9-subunits were identified in all multicellular and unicellular eukaryotic organisms analyzed, but not in prokaryotes or archaeas. Thus, genes encoding CSN subunits present in all analyzed eukaryotes indicate the invention of the signalosome at the root of eukaryotes. The identification of alternative splice variants indicates possible "mini-complexes" or COP9 complexes with independent subunits containing potentially novel and not yet identified functions.},

keywords = {bacteria, evolution, fungi, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Sahyoun:15,

title = {Towards a comprehensive picture of alloacceptor tRNA remolding in metazoan mitochondrial genomes},

author = {Abdullah H Sahyoun and Martin Hölzer and Frank Jühling and Christian {Höner zu Siederdissen} and Marwa Al-Arab and Kifah Tout and Manja Marz and Martin Middendorf and Peter F Stadler and Matthias Bernt},

doi = {10.1093/nar/gkv746},

year  = {2015},

date = {2015-07-30},

urldate = {2015-07-30},

journal = {Nucleic Acids Res},

volume = {43},

number = {16},

pages = {8044--8056},

abstract = {Remolding of tRNAs is a well-documented process in mitochondrial genomes that changes the identity of a tRNA. It involves a duplication of a tRNA gene, a mutation that changes the anticodon and the loss of the ancestral tRNA gene. The net effect is a functional tRNA that is more closely related to tRNAs of a different alloacceptor family than to tRNAs with the same anticodon in related species. Beyond being of interest for understanding mitochondrial tRNA function and evolution, tRNA remolding events can lead to artifacts in the annotation of mitogenomes and thus in studies of mitogenomic evolution. Therefore, it is important to identify and catalog these events. Here we describe novel methods to detect tRNA remolding in large-scale data sets and apply them to survey tRNA remolding throughout animal evolution. We identify several novel remolding events in addition to the ones previously mentioned in the literature. A detailed analysis of these remoldings showed that many of them are derived from ancestral events.},

keywords = {annotation, evolution, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Madhugiri:14,

title = {RNA structure analysis of alphacoronavirus terminal genome regions},

author = {Ramakanth Madhugiri and Markus Fricke and Manja Marz and John Ziebuhr},

doi = {10.1016/j.virusres.2014.10.001},

year  = {2014},

date = {2014-10-13},

urldate = {2014-10-13},

journal = {Virus Res},

volume = {194},

pages = {76--89},

abstract = {Coronavirus genome replication is mediated by a multi-subunit protein complex that is comprised of more than a dozen virally encoded and several cellular proteins. Interactions of the viral replicase complex with cis-acting RNA elements located in the 5' and 3'-terminal genome regions ensure the specific replication of viral RNA. Over the past years, boundaries and structures of cis-acting RNA elements required for coronavirus genome replication have been extensively characterized in betacoronaviruses and, to a lesser extent, other coronavirus genera. Here, we review our current understanding of coronavirus cis-acting elements located in the terminal genome regions and use a combination of bioinformatic and RNA structure probing studies to identify and characterize putative cis-acting RNA elements in alphacoronaviruses. The study suggests significant RNA structure conservation among members of the genus Alphacoronavirus but also across genus boundaries. Overall, the conservation pattern identified for 5' and 3'-terminal RNA structural elements in the genomes of alpha- and betacoronaviruses is in agreement with the widely used replicase polyprotein-based classification of the Coronavirinae, suggesting co-evolution of the coronavirus replication machinery with cognate cis-acting RNA elements.},

keywords = {classification, coronavirus, evolution, RNA / transcriptomics, RNA structure, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Schwartze:14,

title = {Gene expansion shapes genome architecture in the human pathogen \textit{Lichtheimia corymbifera}: an evolutionary genomics analysis in the ancient terrestrial mucorales (Mucoromycotina)},

author = {Volker U. Schwartze and Sascha Winter and Ekaterina Shelest and Marina Marcet-Houben and Fabian Horn and Stefanie Wehner and Jörg Linde and Vito Valiante and Michael Sammeth and Konstantin Riege and Minou Nowrousian and Kerstin Kaerger and Ilse D. Jacobsen and Manja Marz and Axel A. Brakhage and Toni Gabaldón and Sebastian Böcker and Kerstin Voigt},

doi = {10.1371/journal.pgen.1004496},

year  = {2014},

date = {2014-08-14},

urldate = {2014-08-14},

journal = {PLos Genet},

volume = {10},

pages = {e1004496},

abstract = {Lichtheimia species are the second most important cause of mucormycosis in Europe. To provide broader insights into the molecular basis of the pathogenicity-associated traits of the basal Mucorales, we report the full genome sequence of L. corymbifera and compared it to the genome of Rhizopus oryzae, the most common cause of mucormycosis worldwide. The genome assembly encompasses 33.6 MB and 12,379 protein-coding genes. This study reveals four major differences of the L. corymbifera genome to R. oryzae: (i) the presence of an highly elevated number of gene duplications which are unlike R. oryzae not due to whole genome duplication (WGD), (ii) despite the relatively high incidence of introns, alternative splicing (AS) is not frequently observed for the generation of paralogs and in response to stress, (iii) the content of repetitive elements is strikingly low (<5%), (iv) L. corymbifera is typically haploid. Novel virulence factors were identified which may be involved in the regulation of the adaptation to iron-limitation, e.g. LCor01340.1 encoding a putative siderophore transporter and LCor00410.1 involved in the siderophore metabolism. Genes encoding the transcription factors LCor08192.1 and LCor01236.1, which are similar to GATA type regulators and to calcineurin regulated CRZ1, respectively, indicating an involvement of the calcineurin pathway in the adaption to iron limitation. Genes encoding MADS-box transcription factors are elevated up to 11 copies compared to the 1-4 copies usually found in other fungi. More findings are: (i) lower content of tRNAs, but unique codons in L. corymbifera, (ii) Over 25% of the proteins are apparently specific for L. corymbifera. (iii) L. corymbifera contains only 2/3 of the proteases (known to be essential virulence factors) in comparison to R. oryzae. On the other hand, the number of secreted proteases, however, is roughly twice as high as in R. oryzae.},

keywords = {ancient DNA, assembly, evolution, fungi, RNA / transcriptomics, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:14,

title = {Challenges in RNA virus bioinformatics},

author = {Manja Marz and Niko Beerenwinkel and Christian Drosten and Markus Fricke and Dmitrij Frishman and Ivo L Hofacker and Dieter Hoffmann and Martin Middendorf and Thomas Rattei and Peter F Stadler and Armin Töfer},

doi = {10.1093/bioinformatics/btu105},

year  = {2014},

date = {2014-03-03},

urldate = {2014-03-03},

journal = {Bioinformatics},

volume = {30},

number = {13},

pages = {1793--1799},

abstract = {Computer-assisted studies of structure, function and evolution of viruses remains a neglected area of research. The attention of bioinformaticians to this interesting and challenging field is far from commensurate with its medical and biotechnological importance. It is telling that out of >200 talks held at ISMB 2013, the largest international bioinformatics conference, only one presentation explicitly dealt with viruses. In contrast to many broad, established and well-organized bioinformatics communities (e.g. structural genomics, ontologies, next-generation sequencing, expression analysis), research groups focusing on viruses can probably be counted on the fingers of two hands. The purpose of this review is to increase awareness among bioinformatics researchers about the pressing needs and unsolved problems of computational virology. We focus primarily on RNA viruses that pose problems to many standard bioinformatics analyses owing to their compact genome organization, fast mutation rate and low evolutionary conservation. We provide an overview of tools and algorithms for handling viral sequencing data, detecting functionally important RNA structures, classifying viral proteins into families and investigating the origin and evolution of viruses.},

keywords = {classification, evolution, review, RNA / transcriptomics, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Vierna:13,

title = {Systematic analysis and evolution of 5S ribosomal DNA in metazoans},

author = {Joaquin Vierna and Stefanie Wehner and Christian {Höner zu Siederdissen} and Andrés Martínez-Lage and Manja Marz},

doi = {10.1038/hdy.2013.63},

year  = {2013},

date = {2013-07-10},

urldate = {2013-07-10},

journal = {Heredity},

volume = {111},

pages = {410--421},

abstract = {Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12,766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades.},

keywords = {DNA / genomics, evolution, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Li:13,

title = {Identification of purple sea urchin telomerase RNA using a next-generation sequencing based approach},

author = {Yang Li and Joshua D Podlevsky and Manja Marz and Xiaodong Qi and Steve Hoffmann and Peter F Stadler and Julian J-L Chen},

doi = {10.1261/rna.039131.113},

year  = {2013},

date = {2013-04-12},

urldate = {2013-04-12},

journal = {RNA},

volume = {19},

pages = {852--860},

abstract = {Telomerase is a ribonucleoprotein (RNP) enzyme essential for telomere maintenance and chromosome stability. While the catalytic telomerase reverse transcriptase (TERT) protein is well conserved across eukaryotes, telomerase RNA (TR) is extensively divergent in size, sequence, and structure. This diversity prohibits TR identification from many important organisms. Here we report a novel approach for TR discovery that combines in vitro TR enrichment from total RNA, next-generation sequencing, and a computational screening pipeline. With this approach, we have successfully identified TR from Strongylocentrotus purpuratus (purple sea urchin) from the phylum Echinodermata. Reconstitution of activity in vitro confirmed that this RNA is an integral component of sea urchin telomerase. Comparative phylogenetic analysis against vertebrate TR sequences revealed that the purple sea urchin TR contains vertebrate-like template-pseudoknot and H/ACA domains. While lacking a vertebrate-like CR4/5 domain, sea urchin TR has a unique central domain critical for telomerase activity. This is the first TR identified from the previously unexplored invertebrate clade and provides the first glimpse of TR evolution in the deuterostome lineage. Moreover, our TR discovery approach is a significant step toward the comprehensive understanding of telomerase RNP evolution.},

keywords = {evolution, phylogenetics, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Lechner:13,

title = {The correlation of genome size and DNA methylation rate in metazoans},

author = {Marcus Lechner and Manja Marz and Christian Ihling and Andrea Sinz and Peter F Stadler and Veiko Krauss},

doi = {10.1007/s12064-012-0167-y},

year  = {2012},

date = {2012-11-07},

urldate = {2012-11-07},

journal = {Theory Biosci},

volume = {132},

pages = {47--60},

abstract = {Total DNA methylation rates are well known to vary widely between different metazoans. The phylogenetic distribution of this variation, however, has not been investigated systematically. We combine here publicly available data on methylcytosine content with the analysis of nucleotide compositions of genomes and transcriptomes of 78 metazoan species to trace the evolution of abundance and distribution of DNA methylation. The depletion of CpG and the associated enrichment of TpG and CpA dinucleotides are used to infer the intensity and localization of germline CpG methylation and to estimate its evolutionary dynamics. We observe a positive correlation of the relative methylation of CpG motifs with genome size. We tested this trend successfully by measuring total DNA methylation with LC/MS in orthopteran insects with very different genome sizes: house crickets, migratory locusts and meadow grasshoppers. We hypothesize that the observed correlation between methylation rate and genome size is due to a dependence of both variables from long-term effective population size and is driven by the accumulation of repetitive sequences that are typically methylated during periods of small population sizes. This process may result in generally methylated, large genomes such as those of jawed vertebrates. In this case, the emergence of a novel demethylation pathway and of novel reader proteins for methylcytosine may have enabled the usage of cytosine methylation for promoter-based gene regulation. On the other hand, persistently large populations may lead to a compression of the genome and to the loss of the DNA methylation machinery, as observed, e.g., in nematodes.},

keywords = {DNA / genomics, evolution, insects, nucleic acid modifications, phylogenetics},

pubstate = {published},

tppubtype = {article}

}

@article{Qi:13,

title = {The common ancestral core of vertebrate and fungal telomerase RNAs},

author = {Xiaodong Qi and Yang Li and Shinji Honda and Steve Hoffmann and Manja Marz and Axel Mosig and Joshua D Podlevsky and Peter F Stadler and Eric U Selker and Julian J-L Chen},

doi = {10.1093/nar/gks980},

year  = {2012},

date = {2012-10-23},

urldate = {2012-10-23},

journal = {Nucleic Acids Res},

volume = {41},

pages = {450--462},

abstract = {Telomerase is a ribonucleoprotein with an intrinsic telomerase RNA (TER) component. Within yeasts, TER is remarkably large and presents little similarity in secondary structure to vertebrate or ciliate TERs. To better understand the evolution of fungal telomerase, we identified 74 TERs from Pezizomycotina and Taphrinomycotina subphyla, sister clades to budding yeasts. We initially identified TER from Neurospora crassa using a novel deep-sequencing-based approach, and homologous TER sequences from available fungal genome databases by computational searches. Remarkably, TERs from these non-yeast fungi have many attributes in common with vertebrate TERs. Comparative phylogenetic analysis of highly conserved regions within Pezizomycotina TERs revealed two core domains nearly identical in secondary structure to the pseudoknot and CR4/5 within vertebrate TERs. We then analyzed N. crassa and Schizosaccharomyces pombe telomerase reconstituted in vitro, and showed that the two RNA core domains in both systems can reconstitute activity in trans as two separate RNA fragments. Furthermore, the primer-extension pulse-chase analysis affirmed that the reconstituted N. crassa telomerase synthesizes TTAGGG repeats with high processivity, a common attribute of vertebrate telomerase. Overall, this study reveals the common ancestral cores of vertebrate and fungal TERs, and provides insights into the molecular evolution of fungal TER structure and function.},

keywords = {evolution, fungi, phylogenetics},

pubstate = {published},

tppubtype = {article}

}

@article{Dilcher:12,

title = {Genetic characterization of Tribeč virus and Kemerovo virus, two tick-transmitted human-pathogenic Orbiviruses},

author = {Meik Dilcher and Lekbira Hasib and Marcus Lechner and Nicolas Wieseke and Martin Middendorf and Manja Marz and Andrea Koch and Martin Spiegel and Gerhard Dobler and Frank T Hufert and Manfred Weidmann},

doi = {10.1016/j.virol.2011.11.020},

year  = {2011},

date = {2011-12-20},

urldate = {2011-12-20},

journal = {Virology},

volume = {423},

pages = {68--76},

abstract = {We determined the complete genome sequences of Tribeč virus (TRBV) and Kemerovo virus (KEMV), two tick-transmitted Orbiviruses that can cause diseases of the central nervous system and that are currently classified into the Great Island virus serogroup. VP2 proteins of TRBV and KEMV show very low sequence similarity to the homologous VP4 protein of tick-transmitted Great Island virus (GIV). The new sequence data support previous serological classification of these Orbiviruses into the Kemerovo serogroup, which is different from the Great Island virus serogroup. Genome segment 9 of TRBV and KEMV encodes several overlapping ORF's in the +1 reading frame relative to VP6(Hel). A co-phylogenetic analysis indicates a host switch from insect-borne Orbiviruses toward Ixodes species, which is in disagreement with previously published data.},

keywords = {classification, evolution, insects, phylogenetics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Li:11,

title = {RNA-RNA interaction prediction based on multiple sequence alignments},

author = {Andrew X Li and Manja Marz and Jing Qin and Christian M Reidys},

url = {http://www.combinatorics.cn/cbpc/ripalign.html},

doi = {10.1093/bioinformatics/btq659},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Bioinformatics},

volume = {27},

pages = {456--463},

abstract = {Many computerized methods for RNA-RNA interaction structure prediction have been developed. Recently, O(N(6)) time and O(N(4)) space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes. However, few of these methods incorporate the knowledge concerning related sequences, thus relevant evolutionary information is often neglected from the structure determination. Therefore, it is of considerable practical interest to introduce a method taking into consideration both: thermodynamic stability as well as sequence/structure covariation. We present the a priori folding algorithm ripalign, whose input consists of two (given) multiple sequence alignments (MSA). ripalign outputs (i) the partition function, (ii) base pairing probabilities, (iii) hybrid probabilities and (iv) a set of Boltzmann-sampled suboptimal structures consisting of canonical joint structures that are compatible to the alignments. Compared to the single sequence-pair folding algorithm rip, ripalign requires negligible additional memory resource but offers much better sensitivity and specificity, once alignments of suitable quality are given. ripalign additionally allows to incorporate structure constraints as input parameters. The algorithm described here is implemented in C as part of the rip package.},

keywords = {alignment, evolution, RNA structure, RNA-RNA interactions},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:10,

title = {Temperature-dependent structural variability of RNAs: spliced leader RNAs and their evolutionary history},

author = {Manja Marz and Nathalie Vanzo and Peter F Stadler},

doi = {10.1142/S0219720010004525},

year  = {2010},

date = {2010-09-14},

urldate = {2010-01-01},

journal = {J Bioinform Comput Biol},

volume = {8},

number = {1},

pages = {1--17},

abstract = {The structures attained by RNA molecules depend not only on their sequence but also on environmental parameters such as their temperature. So far, this effect has been largely neglected in bioinformatics studies. Here, we show that structural comparisons can be facilitated and more coherent structural models can be obtained when differences in environmental parameters are taken into account. We re-evaluate the secondary structures of the spliced leader (SL) RNAs from the seven eukaryotic phyla in which SL RNA trans-splicing has been described. Adjusting structure prediction to the natural growth temperatures and considering energetically similar secondary structures, we observe striking similarities among Euglenida, Kinetoplastida, Dinophyceae, Cnidaria, Rotifera, Nematoda, Platyhelminthes, and Tunicata that cannot be explained easily by the independent innovation of SL RNAs in each of these phyla. Supplementary Table is available at http://www.worldscinet.com/jbcb/.},

keywords = {evolution, RNA structure, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:09,

title = {Evolution of 7SK RNA and its protein partners in metazoa},

author = {Manja Marz and Alexander Donath and Nina Verstraete and Van Trung Nguyen and Peter F Stadler and Olivier Bensaude},

doi = {10.1093/molbev/msp198},

year  = {2009},

date = {2009-09-04},

urldate = {2009-09-04},

journal = {Mol Biol Evol},

volume = {26},

number = {12},

pages = {2821--2830},

abstract = {7SK RNA is a key player in the regulation of polymerase II transcription. 7SK RNA was considered as a highly conserved vertebrate innovation. The discovery of poorly conserved homologs in several insects and lophotrochozoans, however, implies a much earlier evolutionary origin. The mechanism of 7SK function requires interaction with the proteins HEXIM and La-related protein 7. Here, we present a comprehensive computational analysis of these two proteins in metazoa, and we extend the collection of 7SK RNAs by several additional candidates. In particular, we describe 7SK homologs in Caenorhabditis species. Furthermore, we derive an improved secondary structure model of 7SK RNA, which shows that the structure is quite well-conserved across animal phyla despite the extreme divergence at sequence level.},

keywords = {evolution, ncRNAs, proteins, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:08,

title = {Evolution of spliceosomal snRNA genes in metazoan animals},

author = {Manja Marz and Toralf Kirsten and Peter F Stadler},

doi = {10.1007/s00239-008-9149-6},

year  = {2008},

date = {2008-11-22},

urldate = {2008-11-22},

journal = {J Mol Evol},

volume = {67},

pages = {594--607},

abstract = {While studies of the evolutionary histories of protein families are commonplace, little is known on noncoding RNAs beyond microRNAs and some snoRNAs. Here we investigate in detail the evolutionary history of the nine spliceosomal snRNA families (U1, U2, U4, U5, U6, U11, U12, U4atac, and U6atac) across the completely or partially sequenced genomes of metazoan animals. Representatives of the five major spliceosomal snRNAs were found in all genomes. None of the minor splicesomal snRNAs were detected in nematodes or in the shotgun traces of Oikopleura dioica, while in all other animal genomes at most one of them is missing. Although snRNAs are present in multiple copies in most genomes, distinguishable paralogue groups are not stable over long evolutionary times, although they appear independently in several clades. In general, animal snRNA secondary structures are highly conserved, albeit, in particular, U11 and U12 in insects exhibit dramatic variations. An analysis of genomic context of snRNAs reveals that they behave like mobile elements, exhibiting very little syntenic conservation.},

keywords = {evolution, insects, ncRNAs, RNA structure, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:07,

title = {U7 snRNAs: a computational survey},

author = {Manja Marz and Axel Mosig and Bärbel M R Stadler and Peter F Stadler},

doi = {10.1016/S1672-0229(08)60006-6},

year  = {2008},

date = {2008-02-08},

urldate = {2008-02-08},

journal = {Genomics Proteomics Bioinformatics},

volume = {5},

number = {3-4},

pages = {187--195},

abstract = {U7 small nuclear RNA (snRNA) sequences have been described only for a handful of animal species in the past. Here we describe a computational search for functional U7 snRNA genes throughout vertebrates including the upstream sequence elements characteristic for snRNAs transcribed by polymerase II. Based on the results of this search, we discuss the high variability of U7 snRNAs in both sequence and structure, and report on an attempt to find U7 snRNA sequences in basal deuterostomes and non-drosophilids insect genomes based on a combination of sequence, structure, and promoter features. Due to the extremely short sequence and the high variability in both sequence and structure, no unambiguous candidates were found. These results cast doubt on putative U7 homologs in even more distant organisms that are reported in the most recent release of the Rfam database.},

keywords = {evolution, insects, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Gruber:08,

title = {Invertebrate 7SK snRNAs},

author = {Andreas R Gruber and Dorota Koper-Emde and Manja Marz and Hakim Tafer and Stephan Bernhart and Gregor Obernosterer and Axel Mosig and Ivo L Hofacker and Peter F Stadler and Bernd-Joachim Benecke},

doi = {10.1007/s00239-007-9052-6},

year  = {2008},

date = {2008-01-12},

urldate = {2008-01-12},

journal = {J Mol Evol},

volume = {66},

pages = {107--115},

abstract = {7SK RNA is a highly abundant noncoding RNA in mammalian cells whose function in transcriptional regulation has only recently been elucidated. Despite its highly conserved sequence throughout vertebrates, all attempts to discover 7SK RNA homologues in invertebrate species have failed so far. Here we report on a combined experimental and computational survey that succeeded in discovering 7SK RNAs in most of the major deuterostome clades and in two protostome phyla: mollusks and annelids. Despite major efforts, no candidates were found in any of the many available ecdysozoan genomes, however. The additional sequence data confirm the evolutionary conservation and hence functional importance of the previously described 3' and 5' stem-loop motifs, and provide evidence for a third, structurally well-conserved domain.},

keywords = {evolution, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Washietl:07,

title = {Structured RNAs in the ENCODE selected regions of the human genome},

author = {Stefan Washietl and Jakob S Pedersen and Jan O Korbel and Claudia Stocsits and Andreas R Gruber and Jörg Hackermüller and Jana Hertel and Manja Lindemeyer and Kristin Reiche and Andrea Tanzer and Catherine Ucla and Carine Wyss and Stylianos E Antonarakis and France Denoeud and Julien Lagarde and Jorg Drenkow and Philipp Kapranov and Thomas R Gingeras and Roderic Guigó and Michael Snyder and Mark B Gerstein and Alexandre Reymond and Ivo L Hofacker and Peter F Stadler},

url = {https://www.tbi.univie.ac.at/papers/SUPPLEMENTS/ENCODE/},

doi = {10.1101/gr.5650707},

year  = {2007},

date = {2007-01-01},

urldate = {2007-01-01},

journal = {Genome Res},

volume = {17},

pages = {852--864},

abstract = {Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic-stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to approximately 2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3'-UTRs. While we estimate a significant false discovery rate of approximately 50%-70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).},

keywords = {annotation, evolution, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_92,

title = {Molecular Characterization of Chimeric Staphylococcus aureus Strains from Waterfowl},

author = { Stefan Monecke and Sascha D. Braun and Maximillian Collatz and Celia Diezel and Elke Müller and Martin Reinicke and Adriana Cabal Rosel and Andrea T. Feßler and Dennis Hanke and Igor Loncaric and Stefan Schwarz and Sonia Cortez de Jäckel and Werner Ruppitsch and Dolores Gavier Widen and Helmut Hotzel and Ralf Ehricht},

doi = {10.3390/microorganisms12010096},

journal = {Microorganisms},

volume = {12},

abstract = {Staphylococcus aureus is a versatile pathogen that does not only occur in humans but also in various wild and domestic animals, including several avian species. When characterizing S. aureus isolates from waterfowl, isolates were identified as atypical CC133 by DNA microarray analysis. They differed from previously sequenced CC133 strains in the presence of the collagen adhesin gene cna; some also showed a different capsule type and a deviant spa type. Thus, they were subjected to whole-genome sequencing. This revealed multiple insertions of large regions of DNA from other S. aureus lineages into a CC133-derived backbone genome. Three distinct strains were identified based on the size and extent of these inserts. One strain comprised two small inserts of foreign DNA up- and downstream of oriC; one of about 7000 nt or 0.25% originated from CC692 and the other, at ca. 38,000 nt or 1.3% slightly larger one was of CC522 provenance. The second strain carried a larger CC692 insert (nearly 257,000 nt or 10% of the strain’s genome), and its CC522-derived insert was also larger, at about 53,500 nt or 2% of the genome). The third strain carried an identical CC692-derived region (in which the same mutations were observed as in the second strain), but it had a considerably larger CC522-like insertion of about 167,000 nt or 5.9% of the genome. Both isolates of the first, and two out of four isolates of the second strain also harbored a hemolysin-beta-integrating prophage carrying “bird-specific” virulence factors, ornithine cyclodeaminase D0K6J8 and a putative protease D0K6J9. Furthermore, isolates had two different variants of SCC elements that lacked mecA/mecC genes. These findings highlight the role of horizontal gene transfer in the evolution of S. aureus facilitated by SCC elements, by phages, and by a yet undescribed mechanism for large-scale exchange of core genomic DNA.},

keywords = {bacteria, DNA / genomics, evolution},

pubstate = {published},

tppubtype = {article}

}