Biology subjects

Tran, P.

Publications and source records attributed to Tran, P..

23 records · Page 2Linked to original sources

bioRxiv2020

Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos

Mitochondrial DNA (mtDNA) mutator mice express proofreading-deficient mtDNA polymerase gamma (PolgD257A) and age prematurely1,2, whereas mice with other mitochondrial defects do not show global signs of early aging. The reason for this discrepancy is not completely understood. Hamalainen et al. recently reported that both induced pluripotent stem cells (iPSCs) and primary mutator embryonic fibroblasts harboring PolgD257A demonstrate increased mtDNA replication frequency leading to depletion of the total cellular dNTP pool3. The authors proposed that the decreased availability of cellular dNTPs for nuclear genome replication leads to compromised nuclear genome maintenance and premature aging. Here we report that total cellular dNTP pools are normal in mtDNA mutator mouse embryos (genotype: PolgD257A/D257A), which shows that a living organism exclusively expressing PolgD257A has normal total dNTP pools despite ubiquitous rapid cell division.

cell biology↗

bioRxiv2019

METABOLIC: A scalable high-throughput metabolic and biogeochemical functional trait profiler based on microbial genomes

BackgroundAdvances in microbiome science are being driven in large part due to our ability to study and infer microbial ecology from genomes reconstructed from mixed microbial communities using metagenomics and single-cell genomics. Such omics-based techniques allow us to read genomic blueprints of microorganisms, decipher their functional capacities and activities, and reconstruct their roles in biogeochemical processes. Currently available tools for analyses of genomic data can annotate and depict metabolic functions to some extent, however, no standardized approaches are currently available for the comprehensive characterization of metabolic predictions, metabolite exchanges, microbial interactions, and contributions to biogeochemical cycling. ResultsWe present METABOLIC (METabolic And BiogeOchemistry anaLyses In miCrobes), a scalable software to advance microbial ecology and biogeochemistry using genomes at the resolution of individual organisms and/or microbial communities. The genome-scale workflow includes annotation of microbial genomes, motif validation of biochemically validated conserved protein residues, identification of metabolism markers, metabolic pathway analyses, and calculation of contributions to individual biogeochemical transformations and cycles. The community-scale workflow supplements genome-scale analyses with determination of genome abundance in the community, potential microbial metabolic handoffs and metabolite exchange, and calculation of microbial community contributions to biogeochemical cycles. METABOLIC can take input genomes from isolates, metagenome-assembled genomes, or from single-cell genomes. Results are presented in the form of tables for metabolism and a variety of visualizations including biogeochemical cycling potential, representation of sequential metabolic transformations, and community-scale metabolic networks using a newly defined metric MN-score (metabolic network score). METABOLIC takes [~]3 hours with 40 CPU threads to process [~]100 genomes and metagenomic reads within which the most compute-demanding part of hmmsearch takes [~]45 mins, while it takes [~]5 hours to complete hmmsearch for [~]3600 genomes. Tests of accuracy, robustness, and consistency suggest METABOLIC provides better performance compared to other software and online servers. To highlight the utility and versatility of METABOLIC, we demonstrate its capabilities on diverse metagenomic datasets from the marine subsurface, terrestrial subsurface, meadow soil, deep sea, freshwater lakes, wastewater, and the human gut. ConclusionMETABOLIC enables consistent and reproducible study of microbial community ecology and biogeochemistry using a foundation of genome-informed microbial metabolism, and will advance the integration of uncultivated organisms into metabolic and biogeochemical models. METABOLIC is written in Perl and R and is freely available at https://github.com/AnantharamanLab/METABOLIC under GPLv3.

bioinformatics↗

bioRxiv2019

Age-dependent loss of mitochondrial DNA integrity in mammalian muscle

Ribonucleotides (rNMPs) incorporated in the nuclear genome are a well-established threat to genome stability and can result in DNA strand breaks when not removed in a timely manner. However, the presence of a certain level of rNMPs is tolerated in mitochondrial DNA (mtDNA), although aberrant mtDNA rNMP content has been identified in disease models. We investigated the effect of incorporated rNMPs on mtDNA stability over the mouse lifespan and found that the mtDNA rNMP content increased during early life. The rNMP content of mtDNA varied greatly across different tissues and was defined by the rNTP/dNTP ratio of the tissue. Accordingly, mtDNA rNMPs were nearly absent in SAMHD1-/- mice that have increased dNTP pools. The near absence of rNMPs did not, however, appreciably affect mtDNA copy number or the levels of mtDNA molecules with deletions or strand breaks in aged animals near the end of their lifespan. The physiological rNMP load therefore does not contribute to the progressive loss of mtDNA quality that occurs as mice age.

molecular biology↗

bioRxiv2018

Microbial life under ice: metagenome diversity and in situ activity of Verrucomicrobia in seasonally ice-covered lakes

Northern lakes are ice-covered for a large part of the year, yet our understanding of microbial diversity and activity during winter lags behind that of the ice-free period. In this study, we investigated under-ice diversity and metabolism of Verrucomicrobia in seasonally ice-covered lakes in temperate and boreal regions of Quebec, Canada using 16S rRNA sequencing, metagenomics and metatranscriptomics. Verrucomicrobia, particularly the V1, V3 and V4 subdivisions, were abundant during ice-covered periods. A diversity of Verrucomicrobia genomes were reconstructed from Quebec lake metagenomes. Several genomes were associated with the ice-covered period and were represented in winter metatranscriptomes, supporting the notion that Verrucomicrobia are metabolically active under ice. Verrucomicrobia transcriptome analysis revealed a range of metabolisms potentially occurring under ice, including carbohydrate degradation, glycolate utilization, scavenging of chlorophyll degradation products, and urea use. Genes for aerobic sulfur and hydrogen oxidation were expressed, suggesting chemolithotrophy may be an adaptation to conditions where labile carbon may be limited. The expression of genes for flagella biosynthesis and chemotaxis was detected, suggesting Verrucomicrobia may be actively sensing and responding to winter nutrient pulses, such as phytoplankton blooms. These results increase our understanding on the diversity and metabolic processes occurring under ice in northern lakes ecosystems.

microbiology↗

bioRxiv2018

Genomic evidence for the degradation of terrestrial organic matter by pelagic Arctic Ocean Chloroflexi bacteria

The Arctic Ocean currently receives a large supply of global river discharge and terrestrial dissolved organic matter. Moreover, an increase in freshwater runoff and riverine transport of organic matter to the Arctic Ocean is a predicted consequence of thawing permafrost and increased precipitation. The fate of the terrestrial humic-rich organic material and its impact on the marine carbon cycle are largely unknown. Here, the first metagenomic survey of the Canada Basin in the Western Arctic Ocean showed that pelagic Chloroflexi from the Arctic Ocean are replete with aromatic compound degradation genes, acquired in part by lateral transfer from terrestrial bacteria. Our results imply marine Chloroflexi have the capacity to use terrestrial organic matter and that their role in the carbon cycle may increase with the changing hydrological cycle.

microbiology↗