Neighbor predation linked to natural competence fosters the transfer of large genomic regions in Vibrio cholerae, bioRxiv, 2019-04-25

AbstractNatural competence for transformation is a primary mode of horizontal gene transfer (HGT). Competent bacteria are able to absorb free DNA from their surroundings and exchange this DNA against pieces of their own genome when sufficiently homologous. And while it is known that transformation contributes to evolution and pathogen emergence in bacteria, there are still questions regarding the general prevalence of non-degraded DNA with sufficient coding capacity. In this context, we previously showed that the naturally competent bacterium Vibrio cholerae uses its type VI secretion system (T6SS) to actively acquire DNA from non-kin neighbors under chitin-colonizing conditions. We therefore sought to further explore the role of the T6SS in acquiring DNA, the condition of the DNA released through T6SS-mediated killing versus passive cell lysis, and the extent of the transfers that occur due to these conditions. To do this, we herein measured the frequency and the extent of genetic exchanges in bacterial co-cultures on competence-inducing chitin under various DNA-acquisition conditions. We show that competent V. cholerae strains acquire DNA fragments with an average and maximum length exceeding 50 kbp and 150 kbp, respectively, and that the T6SS is of prime importance for such HGT events. Collectively, our data support the notion that the environmental lifestyle of V. cholerae fosters HGT and that the coding capacity of the exchanged genetic material is sufficient to significantly accelerate bacterial evolution.Significance StatementDNA shuffled from one organism to another in an inheritable manner is a common feature of prokaryotes. It is a significant mechanism by which bacteria acquire new phenotypes, for example by first absorbing foreign DNA and then recombining it into their genome. In this study, we show the remarkable extent of the exchanged genetic material, frequently exceeding 150 genes in a seemingly single transfer event, in Vibrio cholerae. We also show that to best preserve its length and quality, bacteria mainly acquire this DNA by killing adjacent, healthy neighbors then immediately absorbing the released DNA before it can be degraded. These new insights into this prey-killing DNA acquisition process shed light on how bacterial species evolve in the wild.

biorxiv microbiology 0-100-users 2019

RNA transcribed from heterochromatic simple-tandem repeats are required for male fertility and histone-protamine exchange in Drosophila melanogaster, bioRxiv, 2019-04-25

AbstractLong arrays of simple, tandemly repeated DNA sequences (known as satellites) are enriched in centromeres1 and pericentromeric regions2, and contribute to chromosome segregation and other heterochromatin functions3,4. Surprisingly, satellite DNAs are expressed in many multicellular eukaryotes, and their aberrant transcription may contribute to carcinogenesis and cellular toxicity5-7. Satellite transcription andor RNAs may also promote centromere and heterochromatin activities 8-12. However, we lack direct evidence that satellite DNA transcripts are required for normal cell or organismal functions. Here, we show that satellite RNAs derived from AAGAG tandem repeats are transcribed in many cell types throughout Drosophila melanogaster development, enriched in neuronal tissues and testes, localized within heterochromatic regions, and important for viability. Strikingly, we find that AAGAG transcripts are necessary for male fertility and are specifically required for normal histone-protamine exchange and sperm chromatin organization. Since AAGAG RNA-dependent events happen late in spermatogenesis when the transcripts are not detected, we speculate that AAGAG RNA functions in primary spermatocytes to ‘prime’ post-meiosis steps in sperm maturation. In addition to demonstrating specific essential functions for AAGAG RNAs, comparisons between closely related Drosophila species suggest that satellite repeats and their transcription evolve quickly to generate new functions.

biorxiv cell-biology 100-200-users 2019

The gut microbiota influences how circulating immune cells in humans change from one day to the next, bioRxiv, 2019-04-25

ABSTRACTThe gut microbiota influences the development and homeostasis of the mammalian immune system1–3, can alter immune cell compositions in mice4–7, and is associated with responses to immunotherapy that rely on the activity of peripheral immune cells8–12. Still, our understanding of how the microbiota modulates circulatory immune cells remains limited, particularly in humans where a lack of manipulative experiments makes inference challenging. Here we overcome this challenge by studying hundreds of hospitalized—and closely monitored—bone marrow transplantation patients as they recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, allowing the relationships between the two to be studied simultaneously over time with unprecedented resolution. We analyzed daily changes in white blood cell counts from 2,235 patients, and 10,680 longitudinal fecal microbiota samples to identify bacterial genera consistently associated with those changes. Bayesian inference and validation across different patient cohorts revealed consistent associations between intestinal bacteria and peripheral immune cell dynamics in the context of immunomodulatory medications, clinical metadata and homeostatic feedbacks between peripheral immune cells. The quantification of validated microbiota associations enabled us to contrast the potency of fermentatively active, obligate anaerobic bacteria with that of medications with known immunomodulatory mechanism, and this way estimate the microbiota potential to alter peripheral immune cell dynamics directly in patients. Our analysis establishes and quantifies the link between the intestinal microbiota and immune cell dynamics in humans, with implications for microbiota-driven modulation of immunity and immunotherapies that rely on circulatory immune cells.

biorxiv microbiology 100-200-users 2019

 

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