Teleost fishes share a duplication of their entire genomes. We report here on a computational survey of structured non-coding RNAs (ncRNAs) in teleost genomes, focusing on the fate of fish-specific duplicates. As in other metazoan groups, we find evidence of a large number (11,543) of structured RNAs, most of which (~86%) are clade-specific or evolve so fast that their tetrapod homologs cannot be detected. In surprising contrast to protein-coding genes, the fish-specific genome duplication did not lead to a large number of paralogous ncRNAs: only 188 candidates, mostly microRNAs, appear in a larger copy number in teleosts than in tetrapods, suggesting that large-scale gene duplications do not play a major role in the expansion of the vertebrate ncRNA inventory.

Genome-wide multiple sequence alignments (MSAs) are a necessary prerequisite for an increasingly diverse collection of comparative genomic approaches. Here we present a versatile method that generates high-quality MSAs for non-protein-coding sequences. The NcDNAlign pipeline combines pairwise BLAST alignments to create initial MSAs, which are then locally improved and trimmed. The program is optimized for speed and hence is particulary well-suited to pilot studies. We demonstrate the practical use of NcDNAlign in three case studies: the search for ncRNAs in gammaproteobacteria and the analysis of conserved noncoding DNA in nematodes and teleost fish, in the latter case focusing on the fate of duplicated ultra-conserved regions. Compared to the currently widely used genome-wide alignment program TBA, our program results in a 20- to 30-fold reduction of CPU time necessary to generate gammaproteobacterial alignments. A showcase application of bacterial ncRNA prediction based on alignments of both algorithms results in similar sensitivity, false discovery rates, and up to 100 putatively novel ncRNA structures. Similar findings hold for our application of NcDNAlign to the identification of ultra-conserved regions in nematodes and teleosts. Both approaches yield conserved sequences of unknown function, result in novel evolutionary insights into conservation patterns among these genomes, and manifest the benefits of an efficient and reliable genome-wide alignment package. The software is available under the GNU Public License at http://www.bioinf.uni-leipzig.de/Software/NcDNAlign/.

A synthetic proto-organism could be self-assembled by integrating a lipid proto-container with a proto-metabolic subsystem and a proto-genetic subsystem. This three-component system can use energy and nutrients by means of either redox or photo-chemical reactions, evolve its proto-genome by means of template directed replication, and ultimately die. The evolutionary dynamics of the proto-organism depends crucially on the chemical kinetics of its sub-systems and on their interplay. In this work the template replication kinetics is investigated and it is found that the product inhibition inherent in the ligation-like replication process allows for coexistence of unrelated self-replicating proto-genes in the lipid surface layer. The combined catalytic effects from the proto-genes on the metabolic production rates determine the fate of the strain protocell.

The ParaHox cluster contains three Hox‐related homeobox genes. The evolution of this sister of the Hox‐gene clusters has been studied extensively in metazoans with a focus on its early evolution. Its fate within the vertebrate lineage, and in particular following the teleost‐specific genome duplication, however, has not received much attention. Three of the four human ParaHox loci are linked with PDGFR family tyrosine kinases. We demonstrate that these loci arose as duplications in an ancestral vertebrate and trace the subsequent history of gene losses. Surprisingly, teleost fishes have not expanded their ParaHox repertoire following the teleost‐specific genome duplication, while duplicates of the associated tyrosine kinases have survived, supporting the hypothesis of a large‐scale duplication followed by extensive gene loss.

In order to describe a cell at molecular level, a notion of a “gene” is neither necessary nor helpful. It is sufficient to consider the molecules (i.e., chromosomes, transcripts, proteins) and their interactions to describe cellular processes. The downside of the resulting high resolution is that it becomes very tedious to address features on the organismal and phenotypic levels with a language based on molecular terms. Looking for the missing link between biological disciplines dealing with different levels of biological organization, we suggest to return to the original intent behind the term “gene”. To this end, we propose to investigate whether a useful notion of “gene” can be constructed based on an underlying notion of function, and whether this can serve as the necessary link and embed the various distinct gene concepts of biological (sub)disciplines in a coherent theoretical framework. In reply to the Genon Theory recently put forward by Klaus Scherrer and Jürgen Jost in this journal, we shall discuss a general approach to assess a gene definition that should then be tested for its expressiveness and potential cross-disciplinary relevance.

Evolutionarily conserved non-coding genomic sequences represent a potentially rich source for the discovery of gene regulatory regions. Since these elements are subject to stabilizing selection they evolve much slower than adjacent non-functional DNA. These so-called phylogenetic footprints can be detected by comparison of the sequences surrounding orthologous genes in different species. In this paper we present a new method and an effcient software tool for the identifcation of corresponding footprints in long sequences from multiple species. This allows the evolutionary study of the origin and loss of phylogenetic footprints if suffcient number and appropriately placed species are included. We apply this method to the published sequences of HoxA clusters of shark, human, and the duplicated zebrafish and Takifugu clusters as well as the published HoxB cluster sequences. We find that there is a massive loss of sequence conservation in the intergenic region of the HoxA clusters, consistent with the finding in [Chiu et al., PNAS 99, 5492-5497 (2002)]. We further propose a simple model to estimate the loss of sequence conservation that can be attributed to gene loss and other structural reasons. We find that the loss of conservation after cluster duplication is more extensive than expected by this model. This suggests that binding site turnover and/or adaptive modification may also contribute to the loss of sequence conservation. We conclude that this method is suitable for the large scale study of the evolution of (putative) cis-regulatory elements.

The statistical analysis of phylogenetic footprints in the two known horn shark Hox clusters and the four mammalian clusters shows that the shark HoxN cluster is HoxD-like. This finding implies that the most recent common ancestor of jawed vertebrates had at least four Hox clusters, including those which are orthologous to the four mammalian Hox clusters.

The thermodynamics of RNA-RNA interaction consists of two components: the energy necessary to make a potential binding region accessible, i.e., unpaired, and the energy gained from the base pairing of the two interaction partners. We show here that both components can be efficiently computed using an improved variant of RNAup. The method is then applied to a set of bacterial small RNAs involved in translational control. In all cases of biologically active sRNA target interactions, the target sites predicted by RNAup is in perfect agreement with literature. In addition to prediction of target site location, RNAup can be also be used to determine the mode of sRNA action. Using information about target site location and the accessibility change resulting form sRNA binding we can discriminate between positive and negative regulators of translation.

High-throughput experiments have produced convicing evidence for an extensive contribution of diverse classes of RNAs in the expression of genetic information. Instead of a simple arrangement of mostly protein-coding genes, the human tran- scriptome features a complex arrangement of overlapping transcripts, many of which do not code for proteins at all, while others “sample” exons from several different “genes”. The complexity of the transcriptome and the prevalence of non- coding transcripts forces us to reconsider both the concept of the “gene” itself and our understanding of the mechanisms that regulate “gene expression”.

Many classes of non-coding RNAs (ncRNAs; including Y RNAs, vault RNAs, RNase P RNAs, and MRP RNAs, as well as a novel class recently discovered in Dictyostelium discoideum) can be characterized by a pattern of short but well-conserved sequence elements that are separated by poorly conserved regions of sometimes highly variable lengths. Local alignment algorithms such as BLAST are therefore ill-suited for the discovery of new homologs of such ncRNAs in genomic sequences. The Fragrep tool instead implements an efficient algorithm for detecting the pattern fragments that occur in a given order. For each pattern fragment, the mismatch tolerance and bounds on the length of the intervening sequences can be specified separately. Furthermore, matches can be ranked by a statistically well-motivated scoring scheme.