KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States

To characterize the genomic context of New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae isolates from Pakistan and the United States encoding KPC, NDM-1, or no carbapenemase. High similarities of the results indicate rapid spread of carbapenem resistance between strains, including globally disseminated pathogens.     

Community engagement with genetics: public perceptions and expectations about genetics research

Background

Knowledge of molecular biology and genomics continues to expand rapidly, promising numerous opportunities for improving health. However, a key aspect of the success of genomic medicine is related to public understanding and acceptance.

Design

Using community consultations and an online survey, we explored public attitudes and expectations about genomics research.

Results

Thirty‐three members of the general public in Newfoundland, Canada, took part in the community sessions, while 1024 Atlantic Canadians completed the online survey. Overall, many participants noted they lacked knowledge about genetics and associated research and took the opportunity to ask numerous questions throughout sessions. Participants were largely hopeful about genomics research in its capacity to improve health, not only for current residents, but also for future generations. However, they did not accept such research uncritically, and a variety of complex issues and questions arose during the community consultations and were reflected in survey responses.

Discussion

With the proliferation of biobanks and the rapid pace of discoveries in genomics research, public support will be crucial to realize health improvements. If researchers can engage the public in regular, transparent dialogue, this two‐way communication could allow greater understanding of the research process and the design of efficient and effective genetic health services, informed by the public that will use them.     

Why detailed model gene studies in higher eukaryotes are still necessary

Alterations in gene expression programmes are controlled by sequence‐specific DNA‐binding proteins that interact with the epigenetic regulatory machinery. The sum of such processes comprises a gene regulatory network and differentiation processes involve transitions between such networks. However, while great progress has been made to identify network components, this list is not complete, and we still do not fully understand how they work together. In this article, I argue that one reason for this lack of knowledge is the fact that we still do not understand what controls the cell stage and cell state‐specific regulation of individual genes and review examples highlighting this notion.     

The hunt for a yet unknown: Common molecular signature in some genetically monomorphic enterobacteria

Mark Achtman introduced the term “genetically monomorphic bacteria” (GM bacteria) for some human and plant pathogens. They displayed a great uniformity in terms of their “genetic” properties. This “uniformity” poses a challenge to microbiologists. To address these problems, we used CodonW and IslandViewer 3 as analytical tools and took Escherichia coli, Salmonella, and Shigella strains as a model organisms. We hypothesized that GM bacterium contains a common molecular signature among them. We have found a significant correlation regarding the number of protein-coding genes, predicted highly expressed genes, and the highest length of gene in this regard. On the other hand, the correspondence analysis of pathogenicity-related genes identified by IslandViewer 3 displayed a somewhat unique pattern in GM bacteria. The probable pathogenic genes are clustered into two separate groups, which is a hallmark of some pattern. Similar genes of non-monomorphic pathogenic strain clustered almost similarly, but the clusters are joined together, they are not completely separated. These features, in our considered view, may be considered as codon usages signatures of these bacteria, and E. coli in particular.     

Arteriolar responses to vasodilator stimuli and elevated P(O2) in renin congenic and Dahl salt-sensitive rats

OBJECTIVES: Angiotensin II suppression leads to impaired vascular relaxation in normotensive animals on a high-salt diet. The goal of this study was to determine whether normal vascular reactivity could be restored by transferring the chromosomal region carrying the Dahl salt-resistant (R) renin gene into the Dahl salt-sensitive (SS) genetic background in a strain of renin congenic rats (RGRR). METHODS: Male RGRR and SS rats were fed low-salt (0.4%) and high-salt (4%) diets for 4 weeks. The responses of cremaster muscle arterioles to acetylcholine (ACh), sodium nitroprusside (SNP), and elevated PO2 were assessed using video microscopy. RESULTS: ACh-induced dilation was significantly enhanced in RGRR on a high-salt diet compared to SS rats, while dilation to the NO donor SNP was similar in both strains. A high-salt diet significantly enhanced arteriolar constriction in response to elevated PO2, in both SS and RGRR rats. CONCLUSIONS: These data suggest that transfer of the chromosomal region containing the renin gene is crucial in the recovery of ACh-induced dilation of arterioles in RGRR rats vs. SS rats, and that factors in the SS genetic background contribute to an enhanced sensitivity to elevated PO2, independent of genes on chromosome 13.     

Position statement on opportunistic genomic screening from the Association of Genetic Nurses and Counsellors (UK and Ireland)

The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest ‘opportunistic genomic screening'' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients.     

Rapid diversification of five Oryza AA genomes associated with rice adaptation

Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara, Oryza glaberrima, Oryza barthii, Oryza glumaepatula, and Oryza meridionalis. Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.Drawing the landscape of genomic divergence among multiple lineages is fundamental to understanding plant gene and genome evolution (1, 2). The comprehensive comparison of closely related genomes in different chronologically ordered stages under a well-resolved phylogenetic framework could dramatically improve the inference precision and sensitivity of gene evolution studies and should allow more robust results for investigating broad-scale patterns of genomic architecture in the course of the speciation process compared with analyses of single genomes (3, 4). For instance, studies of yeast, Drosophila, and human genomes have demonstrated how comparisons of closely related genome sequences can reveal mechanisms of gene and genome evolution in fungi and animals (5–7). In plants, however, we know little about broad-scale patterns of evolutionary dynamics, differentiation, and consequences. Studies are needed of very closely related plant species that span the speciation continuum and have well-characterized biogeographic histories.The genus Oryza, consisting of 24 species, provides a uniquely powerful system for studying comparative genomics and evolutionary biology, and can contribute to the improvement of rice, which is of pivotal significance in worldwide food production and security (8–10). Many genes involved in rice improvement are derived from wild AA-genome species, and broadening the gene pool of cultivated rice through introgression from other wild relatives of Oryza has attracted increasing attention (11). Phylogenetic analysis of the diploid AA-genome species indicated a closely spaced series of recent speciation events in this genus (12). These species span a wide range of global pantropical regions and are disjunctively distributed in Asia, Africa, Australia, and South America (13). Having diverged less than 3 Mya from a common AA-genome ancestor (12), these eight species have generated extensive adaptive and breeding traits (14, 15).By placing multiple Oryza genome comparisons in a phylogenetic context, previous studies have recorded some of the genomic changes associated with the diversification of the rice genus (16–20). Several studies have compared orthologous genomic segments of Oryza species that represent the different genome types that have diverged over long time scales (18–20). However, none of these analyses provide the full-genome, multispecies perspective that allows comprehensive analysis of gene, genome, or trait evolution.Here, we fully sequenced and assembled de novo the five biogeographically representative AA genomes. In comparison to the high-quality assembly of the O. sativa ssp. japonica cv. Nipponbare (SAT) genome (21), we provide a starting point for studies in the emerging field of comparative and evolutionary genomics. Despite the wealth of phenotypic diversity and adaptive differences, it seems that many attributes of these rice genomes are remarkably conserved across species. Thus, in addition to examining the relationship between sequence and phenotypic diversity, the genomes of these species provide an excellent model for studying, from specific loci to divergent genomic regions, how the evolutionary dynamics of genes and genomes can facilitate speciation processes on a genomic scale. Access to the unprecedented dataset of these Oryza genome sequences will accelerate the pace at which the untapped reservoir of agronomically important genes can be exploited for rice improvement.