Genetic Drift Dominates Genome-Wide Regulatory Evolution Following an Ancient Whole-Genome Duplication in Atlantic Salmon

Whole-genome duplications (WGD) have been considered as springboards that potentiate lineage diversification through increasing functional redundancy. Divergence in gene regulatory elements is a central mechanism for evolutionary diversification, yet the patterns and processes governing regulatory divergence following events that lead to massive functional redundancy, such as WGD, remain largely unknown. We studied the patterns of divergence and strength of natural selection on regulatory elements in the Atlantic salmon (Salmo salar) genome, which has undergone WGD 100–80 Ma. Using ChIPmentation, we first show that H3K27ac, a histone modification typical to enhancers and promoters, is associated with genic regions, tissue-specific transcription factor binding motifs, and with gene transcription levels in immature testes. Divergence in transcription between duplicated genes from WGD (ohnologs) correlated with difference in the number of proximal regulatory elements, but not with promoter elements, suggesting that functional divergence between ohnologs after WGD is mainly driven by enhancers. By comparing H3K27ac regions between duplicated genome blocks, we further show that a longer polyploid state post-WGD has constrained regulatory divergence. Patterns of genetic diversity across natural populations inferred from resequencing indicate that recent evolutionary pressures on H3K27ac regions are dominated by largely neutral evolution. In sum, our results suggest that post-WGD functional redundancy in regulatory elements continues to have an impact on the evolution of the salmon genome, promoting largely neutral evolution of regulatory elements despite their association with transcription levels. These results highlight a case where genome-wide regulatory evolution following an ancient WGD is dominated by genetic drift.Peer reviewe

Genome wide analysis of the complete GlnR nitrogen-response regulon in Mycobacterium smegmatis

BACKGROUND: Nitrogen is an essential element for bacterial growth and an important component of biological macromolecules. Consequently, responding to nitrogen limitation is critical for bacterial survival and involves the interplay of signalling pathways and transcriptional regulation of nitrogen assimilation and scavenging genes. In the soil dwelling saprophyte Mycobacterium smegmatis the OmpR-type response regulator GlnR is thought to mediate the transcriptomic response to nitrogen limitation. However, to date only ten genes have been shown to be in the GlnR regulon, a vastly reduced number compared to other organisms. RESULTS: We investigated the role of GlnR in the nitrogen limitation response and determined the entire GlnR regulon, by combining expression profiling of M. smegmatis wild type and glnR deletion mutant, with GlnR-specific chromatin immunoprecipitation and high throughput sequencing. We identify 53 GlnR binding sites during nitrogen limitation that control the expression of over 100 genes, demonstrating that GlnR is the regulator controlling the assimilation and utilisation of nitrogen. We also determine a consensus GlnR binding motif and identify key residues within the motif that are required for specific GlnR binding. CONCLUSIONS: We have demonstrated that GlnR is the global nitrogen response regulator in M. smegmatis, directly regulating the expression of more than 100 genes. GlnR controls key nitrogen stress survival processes including primary nitrogen metabolism pathways, the ability to utilise nitrate and urea as alternative nitrogen sources, and the potential to use cellular components to provide a source of ammonium. These studies further our understanding of how mycobacteria survive nutrient limiting conditions

Attributable costs of surgical site infection and endometritis after low transverse cesarean delivery

BACKGROUND: Accurate data on costs attributable to hospital-acquired infections are needed in order to determine their economic impact and the cost-benefit of potential preventive strategies. OBJECTIVE: Determine the attributable costs of surgical site infection (SSI) and endometritis (EMM) after cesarean section using two different methods. DESIGN: Retrospective cohort. SETTING: Barnes-Jewish Hospital, a 1250-bed academic tertiary care hospital. PATIENTS: 1,605 women who underwent low transverse cesarean section from 7/1999 – 6/2001. METHODS: Attributable costs of SSI and EMM were determined by generalized least squares (GLS) and propensity score matched-pairs using administrative claims data to define underlying comorbidities and procedures. For the matched-pairs analyses, uninfected control patients were matched to patients with SSI or with EMM based on their propensity to develop infection, and the median difference in costs calculated. RESULTS: The attributable total hospital cost of SSI calculated by GLS was $3,529 and by propensity score matched-pairs was$2,852. The attributable total hospital cost of EMM calculated by GLS was $3,956 and by propensity score matched-pairs was$3,842. The majority of excess costs were associated with room and board and pharmacy costs. CONCLUSIONS: The costs of SSI and EMM were lower than SSI costs reported after more extensive operations. The attributable costs of EMM calculated using the two methods were very similar, while the costs of SSI calculated using propensity score matched-pairs were lower than the costs calculated by GLS. The difference in costs determined by the two methods needs to be considered by investigators performing cost analyses of hospital-acquired infections

Dissociation of sensitivity to spatial frequency in word and face preferential areas of the fusiform gyrus

Different cortical regions within the ventral occipitotemporal junction have been reported to show preferential responses to particular objects. Thus, it is argued that there is evidence for a left-lateralized visual word form area and a right-lateralized fusiform face area, but the unique specialization of these areas remains controversial. Words are characterized by greater power in the high spatial frequency (SF) range, whereas faces comprise a broader range of high and low frequencies. We investigated how these high-order visual association areas respond to simple sine-wave gratings that varied in SF. Using functional magnetic resonance imaging, we demonstrated lateralization of activity that was concordant with the low-level visual property of words and faces; left occipitotemporal cortex is more strongly activated by high than by low SF gratings, whereas the right occipitotemporal cortex responded more to low than high spatial frequencies. Therefore, the SF of a visual stimulus may bias the lateralization of processing irrespective of its higher order properties

Distributing Power: A transition to a civic energy future

There is growing interest, from a range of stakeholders, in the potential of distributed low-carbon electricity generation in delivering a low-carbon energy system. Yet there are still significant gaps in understanding, particularly regarding the feasibility of scaling up distributed generation from technological, governance, regulation, policy, and financial perspectives. The aim of this report is to address these gaps within the context of the Thousand Flowers pathway

Colour Peak:An analogue environment for the waters of late Noachian Mars

The surface of Mars cannot sustain liquid water today, but there is evidence water was present during the Noachian era. The transition of the martian climate from the wet Noachian to the dry Hesperian would have resulted in saline and sulfur rich surface waters . Terrestrial analogue environments that possess a chemistry like these proposed waters can be used to develop an understanding of organisms that could have persisted under such conditions. Here we present the chemistry and microbiome of the analogue environment Colour Peak, a sulfidic and saline spring system located within the Canadian High Arctic. In this study, molecular and geochemical techniques were used to investigate the sediment of the Colour Peak springs. Nucleic acids were extracted from the microbes in the sediments and the microbiome was characterised by the amplification and sequencing of 16S rRNA gene amplicons. The elemental composition of the fluids and sediment was determined by ICP-OES and compared with brines determined from the chemistry of the “Rocknest” sand sample at Yellowknife Bay, Gale Crater (Mars) by thermochemical modelling. Gibbs energy values were calculated from this fluid chemistry to identify potentially viable metabolisms. Analysis of the chemistries of the Colour Peak fluids confirmed a chemical composition like the thermochemically modelled fluid, with this justifying the classification of Colour Peak as an appropriate analogue environment to investigate the habitability of former martian aqueous environments. 16S rRNA gene profiling of the Colour Peak microbial community revealed it was dominated by bacteria associated with oxidation of reduced sulfur species and carbon dioxide fixation. Gibbs energy values calculated using the chemistry of the modelled martian fluid demonstrated that the oxidation of reduced sulfur species was also viable in this chemical environment under aerobic and anaerobic conditions. These results demonstrate that microbial sulfide oxidation is thermodynamically viable using both modelled and environmental proxies for former martian aqueous environments. This study highlights that metabolisms utilising the oxidation of reduced sulfur species could have been thermodynamically viable in ancient martian aqueous environments. Further work is needed to assess this proposed viability and the potential for unambiguous biosignature formation