Familiarity and strangeness: seeing everyday practices of punishment and resistance in Holloway Prison

London’s Holloway Prison, the largest women’s prison in western Europe, closed in 2016. The impact of the closure on the women incarcerated in Holloway, and the prison’s place in the local community, is the focus of a project led by Islington Museum. Here, we develop an innovation, emotion-led methodology to explore photographs of the decommissioned Holloway, asking what they communicate about experiences of imprisonment and practices of punishment. The images illustrate the strategies of control, mechanisms of punishment and tactics of resistance that operate through the carceral space. From a feminist, anti-carceral perspective, we emphasise the importance of seeing prison spaces and attending to the emotional responses generated. We offer a creative intervention into dominant government and media narratives of Holloway’s closure and suggest that considering what it is that feels familiar and strange about carceral spaces has the potential to operate as a form of anti-carceral work

FRAGS: estimation of coding sequence substitution rates from fragmentary data

BACKGROUND: Rates of substitution in protein-coding sequences can provide important insights into evolutionary processes that are of biomedical and theoretical interest. Increased availability of coding sequence data has enabled researchers to estimate more accurately the coding sequence divergence of pairs of organisms. However the use of different data sources, alignment protocols and methods to estimate substitution rates leads to widely varying estimates of key parameters that define the coding sequence divergence of orthologous genes. Although complete genome sequence data are not available for all organisms, fragmentary sequence data can provide accurate estimates of substitution rates provided that an appropriate and consistent methodology is used and that differences in the estimates obtainable from different data sources are taken into account. RESULTS: We have developed FRAGS, an application framework that uses existing, freely available software components to construct in-frame alignments and estimate coding substitution rates from fragmentary sequence data. Coding sequence substitution estimates for human and chimpanzee sequences, generated by FRAGS, reveal that methodological differences can give rise to significantly different estimates of important substitution parameters. The estimated substitution rates were also used to infer upper-bounds on the amount of sequencing error in the datasets that we have analysed. CONCLUSION: We have developed a system that performs robust estimation of substitution rates for orthologous sequences from a pair of organisms. Our system can be used when fragmentary genomic or transcript data is available from one of the organisms and the other is a completely sequenced genome within the Ensembl database. As well as estimating substitution statistics our system enables the user to manage and query alignment and substitution data

Inference of Candidate Germline Mutator Loci in Humans from Genome-Wide Haplotype Data

The rate of germline mutation varies widely between species but little is known about the extent of variation in the germline mutation rate between individuals of the same species. Here we demonstrate that an allele that increases the rate of germline mutation can result in a distinctive signature in the genomic region linked to the affected locus, characterized by a number of haplotypes with a locally high proportion of derived alleles, against a background of haplotypes carrying a typical proportion of derived alleles. We searched for this signature in human haplotype data from phase 3 of the 1000 Genomes Project and report a number of candidate mutator loci, several of which are located close to or within genes involved in DNA repair or the DNA damage response. To investigate whether mutator alleles remained active at any of these loci, we used $\textit{de novo}$ mutation counts from human parent-offspring trios in the 1000 Genomes and Genome of the Netherlands cohorts, looking for an elevated number of $\textit{de novo}$ mutations in the offspring of parents carrying a candidate mutator haplotype at each of these loci. We found some support for two of the candidate loci, including one locus just upstream of the $\textit{BRSK2}$ gene, which is expressed in the testis and has been reported to be involved in the response to DNA damage

Sorting signed circular permutations by super short reversals

We consider the problem of sorting a circular permutation by reversals of length at most 2, a problem that finds application in comparative genomics. Polynomial-time solutions for the unsigned version of this problem are known, but the signed version remained open. In this paper, we present the first polynomial-time solution for the signed version of this problem. Moreover, we perform an experiment for inferring distances and phylogenies for published Yersinia genomes and compare the results with the phylogenies presented in previous works.We consider the problem of sorting a circular permutation by reversals of length at most 2, a problem that finds application in comparative genomics. Polynomial-time solutions for the unsigned version of this problem are known, but the signed version rema9096272283FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2013/08293-72014/04718-6306730/2012-0; 477692/2012-5; 483370/2013-411th International Symposium on Bioinformatics Research and Application

Why highly expressed proteins evolve slowly

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions, and can explain why highly expressed proteins evolve slowly across the tree of life.Comment: 40 pages, 3 figures, with supporting informatio

Epitope Discovery with Phylogenetic Hidden Markov Models

Existing methods for the prediction of immunologically active T-cell epitopes are based on the amino acid sequence or structure of pathogen proteins. Additional information regarding the locations of epitopes may be acquired by considering the evolution of viruses in hosts with different immune backgrounds. In particular, immune-dependent evolutionary patterns at sites within or near T-cell epitopes can be used to enhance epitope identification. We have developed a mutation–selection model of T-cell epitope evolution that allows the human leukocyte antigen (HLA) genotype of the host to influence the evolutionary process. This is one of the first examples of the incorporation of environmental parameters into a phylogenetic model and has many other potential applications where the selection pressures exerted on an organism can be related directly to environmental factors. We combine this novel evolutionary model with a hidden Markov model to identify contiguous amino acid positions that appear to evolve under immune pressure in the presence of specific host immune alleles and that therefore represent potential epitopes. This phylogenetic hidden Markov model provides a rigorous probabilistic framework that can be combined with sequence or structural information to improve epitope prediction. As a demonstration, we apply the model to a data set of HIV-1 protein-coding sequences and host HLA genotypes

Sorting Signed Circular Permutations by Super Short Reversals

International audienceWe consider the problem of sorting a circular permutation by reversals of length at most 2, a problem that finds application in comparative genomics. Polynomial-time solutions for the unsigned version of this problem are known, but the signed version remained open. In this paper, we present the first polynomial-time solution for the signed version of this problem. Moreover, we perform an experiment for inferring distances and phylogenies for published Yersinia genomes and compare the results with the phylogenies presented in previous works

A Model for the Evolution of Nucleotide Polymerase Directionality

Background: In all known living organisms, every enzyme that synthesizes nucleic acid polymers does so by adding nucleotide 59-triphosphates to the 39-hydroxyl group of the growing chain. This results in the well known 5’?3’ directionality of all DNA and RNA Polymerases. The lack of any alternative mechanism, e.g. addition in a 3’?5 ’ direction, may indicate a very early founder effect in the evolution of life, or it may be the result of a selective pressure against such an alternative. Methodology/Principal Findings: In an attempt to determine whether the lack of an alternative polymerase directionality is the result of a founder effect or evolutionary selection, we have constructed a basic model of early polymerase evolution. This model is informed by the essential chemical properties of the nucleotide polymerization reaction. With this model, we are able to simulate the growth of organisms with polymerases that synthesize either 5’?3 ’ or 3’?5 ’ in isolation or in competition with each other. Conclusions/Significance: We have found that a competition between organisms with 5’?3 ’ polymerases and 3’?5’ polymerases only results in a evolutionarily stable strategy under certain conditions. Furthermore, we have found that mutations lead to a much clearer delineation between conditions that lead to a stable coexistence of these populations and conditions which ultimately lead to success for the 5’?3 ’ form. In addition to presenting a plausible explanation for th

Correcting the Bias of Empirical Frequency Parameter Estimators in Codon Models

Markov models of codon substitution are powerful inferential tools for studying biological processes such as natural selection and preferences in amino acid substitution. The equilibrium character distributions of these models are almost always estimated using nucleotide frequencies observed in a sequence alignment, primarily as a matter of historical convention. In this note, we demonstrate that a popular class of such estimators are biased, and that this bias has an adverse effect on goodness of fit and estimates of substitution rates. We propose a “corrected” empirical estimator that begins with observed nucleotide counts, but accounts for the nucleotide composition of stop codons. We show via simulation that the corrected estimates outperform the de facto standard estimates not just by providing better estimates of the frequencies themselves, but also by leading to improved estimation of other parameters in the evolutionary models. On a curated collection of sequence alignments, our estimators show a significant improvement in goodness of fit compared to the approach. Maximum likelihood estimation of the frequency parameters appears to be warranted in many cases, albeit at a greater computational cost. Our results demonstrate that there is little justification, either statistical or computational, for continued use of the -style estimators

Mutational Biases and Selective Forces Shaping the Structure of Arabidopsis Genes

Recently features of gene expression profiles have been associated with structural parameters of gene sequences in organisms representing a diverse set of taxa. The emerging picture indicates that natural selection, mediated by gene expression profiles, has a significant role in determining genic structures. However the current situation is less clear in plants as the available data indicates that the effect of natural selection mediated by gene expression is very weak. Moreover, the direction of the patterns in plants appears to contradict those observed in animal genomes. In the present work we analized expression data for >18000 Arabidopsis genes retrieved from public datasets obtained with different technologies (MPSS and high density chip arrays) and compared them with gene parameters. Our results show that the impact of natural selection mediated by expression on genes sequences is significant and distinguishable from the effects of regional mutational biases. In addition, we provide evidence that the level and the breadth of gene expression are related in opposite ways to many structural parameters of gene sequences. Higher levels of expression abundance are associated with smaller transcripts, consistent with the need to reduce costs of both transcription and translation. Expression breadth, however, shows a contrasting pattern, i.e. longer genes have higher breadth of expression, possibly to ensure those structural features associated with gene plasticity. Based on these results, we propose that the specific balance between these two selective forces play a significant role in shaping the structure of Arabidopsis genes