Biology subjects

Stadler, P. F.

Publications and source records attributed to Stadler, P. F..

6 recordsLinked to original sources

bioRxiv2018

TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes

AbstractThe telomerase RNA in yeasts is large, usually > 1,000 nt, and contains functional elements that have been extensively studied experimentally in several disparate species. Nevertheless, they are very difficult to detect by homology-based methods and so far have escaped annotation in the majority of the genomes of Saccharomycotina. This is a consequence of sequences that evolve rapidly at nucleotide level, are subject to large variations in size, and are highly plastic with respect to their secondary structures. Here we report on a survey that was aimed at closing this gap in RNA annotation. Despite considerable efforts and the combination of a variety of different methods, it was only partially successful. While 27 new telomerase RNAs were identified, we had to restrict our efforts to the subgroup Saccharomycetacea because even this narrow subgroup was diverse enough to require different search models for different phylogenetic subgroups. More distant branches of the Saccharomycotina still remain without annotated telomerase RNA.

bioinformatics↗

bioRxiv2018

Genome-wide features of introns are evolutionary decoupled among themselves and from genome size throughout Eukarya

The impact of spliceosomal introns on genome and organismal evolution remains puzzling. Here, we investigated the correlative associations among genome-wide features of introns from protein-coding genes (e.g., size, density, genome-content, repeats), genome size and multicellular complexity on 461 eukaryotes. Thus, we formally distinguished simple from complex multicellular organisms (CMOs), and developed the program GenomeContent to systematically estimate genomic traits. We performed robust phylogenetic controlled analyses, by taking into account significant uncertainties in the tree of eukaryotes and variation in genome size estimates. We found that changes in the variation of some intron features (such as size and repeat composition) are only weakly, while other features measuring intron abundance (within and across genes) are not, scaling with changes in genome size at the broadest phylogenetic scale. Accordingly, the strength of these associations fluctuates at the lineage-specific level, and changes in the length and abundance of introns within a genome are found to be largely evolving independently throughout Eukarya. Thereby, our findings are in disagreement with previous estimations claiming a concerted evolution between genome size and introns across eukaryotes. We also observe that intron features vary homogeneously (with low repetitive composition) within fungi, plants and stramenophiles; but they vary dramatically (with higher repetitive composition) within holozoans, chlorophytes, alveolates and amoebozoans. We also found that CMOs and their closest ancestral relatives are characterized by high intron-richness, regardless their genome size. These patterns contrast the narrow distribution of exon features found across eukaryotes. Collectively, our findings unveil spliceosomal introns as a dynamically evolving non-coding DNA class and strongly argue against both, a particular intron feature as key determinant of eukaryotic gene architecture, as well as a major mechanism (adaptive or non-adaptive) behind the evolutionary dynamics of introns over a large phylogenetic scale. We hypothesize that intron-richness is a pre-condition to evolve complex multicellularity.

evolutionary biology↗

bioRxiv2017

Time-Consistent Reconciliation Maps and ForbiddenTime Travel

BackgroundIn the absence of horizontal gene transfer it is possible to reconstruct the history of gene families from empirically determined orthology relations, which are equivalent to event-labeled gene trees. Knowledge of the event labels considerably simplifies the problem of reconciling a gene tree T with a species trees S, relative to the reconciliation problem without prior knowledge of the event types. It is well-known that optimal reconciliations in the unlabeled case may violate time-consistency and thus are not biologically feasible. Here we investigate the mathematical structure of the event labeled reconciliation problem with horizontal transfer.\n\nResultsWe investigate the issue of time-consistency for the event-labeled version of the reconciliation problem, provide a convenient axiomatic framework, and derive a complete characterization of time-consistent reconciliations. This characterization depends on certain weak conditions on the event-labeled gene trees that reflect conditions under which evolutionary events are observable at least in principle. We give an [O](|V(T)|log(|V(S)|))-time algorithm to decide whether a time-consistent reconciliation map exists. It does not require the construction of explicit timing maps, but relies entirely on the comparably easy task of checking whether a small auxiliary graph is acyclic. The algorithms are implemented in C++ using the boost graph library and are freely available at https://github.com/Nojgaard/tc-recon.\n\nSignificanceThe combinatorial characterization of time consistency and thus biologically feasible reconciliation is an important step towards the inference of gene family histories with horizontal transfer from orthology data, i.e., without presupposed gene and species trees. The fast algorithm to decide time consistency is useful in a broader context because it constitutes an attractive component for all tools that address tree reconciliation problems.

evolutionary biology↗

bioRxiv2017

Large-Scale Evolutionary Patterns of Protein Domain Distributions in Eukaryotes

The genomic inventory of protein domains is an important indicator of an organisms regulatory and metabolic capabilities. Existing gene annotations, however, can be plagued by substantial ascertainment biases that make it difficult to obtain and compare quantitative domain data. We find that quantitative trends across the Eukarya can be investigated based on a combination of gene prediction and standard domain annotation pipelines. Species-specific training is required, however, to account for the genomic peculiarities in many lineages. In contrast to earlier studies we find wide-spread statistically significant avoidance of protein domains associated with distinct functional high-level gene-ontology terms.\n\n1998 ACM Subject Classification J.3 Life and Medical Sciences

bioinformatics↗

bioRxiv2017

Alzheimer related genes show accelerated evolution

Alzheimer's disease (AD) is a neurodegenerative disorder of unknown cause with complex genetic and environmental traits. Here, we show that gene structures of loci, that show AD-associated changes in their expression, evolve faster than the genome at large. This phylogenetic trait of AD suggests a critical pathogenetic role of recent adaptive evolution of human brain and might have far reaching consequences with respect to the appropriateness of model systems and the development of disease-modifying strategies.

evolutionary biology↗

bioRxiv2016

Design Specifications for Cellular Regulation

A critical feature of all cellular processes is the ability to control the rate of gene or protein expression and metabolic flux in changing environments through regulatory feedback. We review the many ways that regulation is represented through causal, logical and dynamical components. Formalizing the nature of these components promotes effective comparison among distinct regulatory networks and provides a common framework for the potential design and control of regulatory systems in synthetic biology.

systems biology↗