Transfer RNA genes experience exceptionally elevated mutation rates.

Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations

Codon Bias Patterns of E.coliE.coli's Interacting Proteins

Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino acid, are used differently across the variety of living organisms. The biological meaning of this phenomenon, known as codon usage bias, is still controversial. In order to shed light on this point, we propose a new codon bias index, $CompAI$, that is based on the competition between cognate and near-cognate tRNAs during translation, without being tuned to the usage bias of highly expressed genes. We perform a genome-wide evaluation of codon bias for $E.coli$, comparing $CompAI$ with other widely used indices: $tAI$, $CAI$, and $Nc$. We show that $CompAI$ and $tAI$ capture similar information by being positively correlated with gene conservation, measured by ERI, and essentiality, whereas, $CAI$ and $Nc$ appear to be less sensitive to evolutionary-functional parameters. Notably, the rate of variation of $tAI$ and $CompAI$ with ERI allows to obtain sets of genes that consistently belong to specific clusters of orthologous genes (COGs). We also investigate the correlation of codon bias at the genomic level with the network features of protein-protein interactions in $E.coli$. We find that the most densely connected communities of the network share a similar level of codon bias (as measured by $CompAI$ and $tAI$). Conversely, a small difference in codon bias between two genes is, statistically, a prerequisite for the corresponding proteins to interact. Importantly, among all codon bias indices, $CompAI$ turns out to have the most coherent distribution over the communities of the interactome, pointing to the significance of competition among cognate and near-cognate tRNAs for explaining codon usage adaptation

Undetected antisense tRNAs in mitochondrial genomes?

<p>Abstract</p> <p>Background</p> <p>The hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Antisense tRNA expression is plausible because tRNA punctuation signals mt sense RNA maturation: both sense and antisense tRNAs form secondary structures potentially signalling processing. Sense RNA maturation processes by default 11 antisense tRNAs neighbouring sense genes. If antisense tRNAs are expressed, processed antisense tRNAs should have adapted more for translational activity than unprocessed ones. Four tRNA properties are examined: antisense tRNA 5' and 3' end processing by sense RNA maturation and its accuracy, cloverleaf stability and misacylation potential.</p> <p>Results</p> <p>Processed antisense tRNAs align better with standard tRNA sequences with the same cognate than unprocessed antisense tRNAs, suggesting less misacylations. Misacylation increases with cloverleaf fragility and processing inaccuracy. Cloverleaf fragility, misacylation and processing accuracy of antisense tRNAs decrease with genome-wide usage of their predicted cognate amino acid.</p> <p>Conclusions</p> <p>These properties correlate as if they adaptively coevolved for translational activity by some antisense tRNAs, and to avoid such activity by other antisense tRNAs. Analyses also suggest previously unsuspected particularities of aminoacylation specificity in mt tRNAs: combinations of competition between tRNAs on tRNA synthetases with competition between tRNA synthetases on tRNAs determine specificities of tRNA amino acylations. The latter analyses show that alignment methods used to detect tRNA cognates yield relatively robust results, even when they apparently fail to detect the tRNA's cognate amino acid and indicate high misacylation potential.</p> <p>Reviewers</p> <p>This article was reviewed by Dr Juergen Brosius, Dr Anthony M Poole and Dr Andrei S Rodin (nominated by Dr Rob Knight).</p

Long-Range Periodic Patterns in Microbial Genomes Indicate Significant Multi-Scale Chromosomal Organization

Genome organization can be studied through analysis of chromosome position-dependent patterns in sequence-derived parameters. A comprehensive analysis of such patterns in prokaryotic sequences and genome-scale functional data has yet to be performed. We detected spatial patterns in sequence-derived parameters for 163 chromosomes occurring in 135 bacterial and 16 archaeal organisms using wavelet analysis. Pattern strength was found to correlate with organism-specific features such as genome size, overall GC content, and the occurrence of known motility and chromosomal binding proteins. Given additional functional data for Escherichia coli, we found significant correlations among chromosome position dependent patterns in numerous properties, some of which are consistent with previously experimentally identified chromosome macrodomains. These results demonstrate that the large-scale organization of most sequenced genomes is significantly nonrandom, and, moreover, that this organization is likely linked to genome size, nucleotide composition, and information transfer processes. Constraints on genome evolution and design are thus not solely dependent upon information content, but also upon an intricate multi-parameter, multi-length-scale organization of the chromosome

A tRNA world

Knowledge about the kinetics of chemical reactions in cells is important for an understanding of signaling pathways and regulation. Even though there are many kinetic measurements of in vitro reactions in literature, methods for in vivo measurements are sparse. With help of Temperature Oscillation Optical Lock-in (TOOL) microscopy we measure the kinetics of DNA hybridization inside cells and detect signicant acceleration or deceleration compared to in vitro measurements, dependent on the DNA sample. The dierences can not be explained by molecular crowding eects. Only models that take the background interactions with genomic DNA and RNA as well as the activity of single stranded and double stranded binding proteins into account, can be tted to data. The results imply that the biological relevance of kinetic rates measured in vitro has to be rejudged carefully. The RNA world hypothesis predicts catalytic molecules based on RNA, as for example early replicators, as precursor of modern biology. But how can a pool of appropriate RNA molecules arise under early earth conditions? In a Gillespie-model, we observe the length distribution, secondary structure and sequences of a pool of RNA molecules in porous rocks like they appear near sites of volcanic activity. We assume a monomer in ux, a length dependent out ux, a random, non-templated polymerisation and a degradation that is much stronger for single stranded than for double stranded RNA. After equilibrium is reached, the pool is populated with many hairpin-like structures due to the selection pressure for hybridized strands that can be bricks for RNA machines. Once sequence motifs and their complements appear in the reactor, they protect each other and are present longer than statistically expected. This "protection by hybridization" has the same ngerprint as a weak replication. As a consequence, the pool does not cover the full sequence space but includes more similar sequences, which is an important condition for chemical reactions. Replication of genetic information by RNA molecules is considered to be a key process in the beginning of evolution. It is so crucial that traces of this early replication are expected to be present in key processes of modern biology. We present a replication scheme based on hairpins derived from the sequence of tRNA that replicates the genetic information about a succession of sequence snippets. The replication is driven by temperature oscillations as they occur naturally inside of porous rocks in presence of temperature gradients, and independent on external chemical energy sources. It is selective for correct information and shows exponential growth rates with doubling times in the range of seconds to minutes and is thereby the fastest early replicator in the literature. The replication scheme can naturally be expanded to longer successions by using double hairpins derived from full tRNA sequences by only few mutations. By charging double hairpins with amino acids or peptides, the proposed replication bridges the gap from the RNA world to modern biology by oering a rudimentary translation mechanism, that sorts amino acids to chains according to genetic information

The Complete Chloroplast and Mitochondrial Genome Sequences of Boea hygrometrica: Insights into the Evolution of Plant Organellar Genomes

The complete nucleotide sequences of the chloroplast (cp) and mitochondrial (mt) genomes of resurrection plant Boea hygrometrica (Bh, Gesneriaceae) have been determined with the lengths of 153,493 bp and 510,519 bp, respectively. The smaller chloroplast genome contains more genes (147) with a 72% coding sequence, and the larger mitochondrial genome have less genes (65) with a coding faction of 12%. Similar to other seed plants, the Bh cp genome has a typical quadripartite organization with a conserved gene in each region. The Bh mt genome has three recombinant sequence repeats of 222 bp, 843 bp, and 1474 bp in length, which divide the genome into a single master circle (MC) and four isomeric molecules. Compared to other angiosperms, one remarkable feature of the Bh mt genome is the frequent transfer of genetic material from the cp genome during recent Bh evolution. We also analyzed organellar genome evolution in general regarding genome features as well as compositional dynamics of sequence and gene structure/organization, providing clues for the understanding of the evolution of organellar genomes in plants. The cp-derived sequences including tRNAs found in angiosperm mt genomes support the conclusion that frequent gene transfer events may have begun early in the land plant lineage

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 161 reports, articles, and other documents introduced into the NASA scientific and technical information system in November, 1987