Abstract
Ancestral state reconstruction is not only a fundamental tool for studying trait evolution, but also very useful for predicting the unknown trait values (hidden states) of extant species. A ...well-known problem in ancestral and hidden state predictions is that the uncertainty associated with predictions can be so large that predictions themselves are of little use. Therefore, for meaningful interpretation of predicted traits and hypothesis testing, it is prudent to accurately assess the uncertainty of the predictions. Commonly used constant-rate Brownian motion (BM) model fails to capture the complexity of tempo and mode of trait evolution in nature, making predictions under the BM model vulnerable to lack-of-fit errors from model misspecification. Using empirical data (mammalian body size and bacterial genome size), we show that the distribution of residual Z-scores under the BM model is neither homoscedastic nor normal as expected. Consequently, the 95% confidence intervals of predicted traits are so unreliable that the actual coverage probability ranges from 33% (strongly permissive) to 100% (strongly conservative). Alternative methods such as BayesTraits and StableTraits that allow variable rates in evolution improve the predictions but are computationally expensive. Here, we develop Reconstructing Ancestral State under Pulsed Evolution in R by Gaussian Decomposition (RasperGade), a method of ancestral and hidden state prediction that uses the Levy process to explicitly model gradual evolution, pulsed evolution, and time-independent variation. Using the same empirical data, we show that RasperGade outperforms both BayesTraits and StableTraits in providing reliable confidence estimates and is orders-of-magnitude faster. Our results suggest that, when predicting the ancestral and hidden states of continuous traits, the rate variation should always be assessed and the quality of confidence estimates should always be examined. Bacterial genomic traits; model misspecification; trait evolution.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Large-scale, genome-level molecular phylogenetic analyses present both opportunities and challenges for bacterial evolutionary and ecological studies. We constructed a phylum-level bacterial ...phylogenetic marker database by surveying all complete bacterial genomes and identifying single-copy genes that were widely distributed in each of the 20 bacterial phyla. We showed that phylum trees made using these markers were highly resolved and were more robust than the bacterial genome tree based on 31 universal bacterial marker genes. In addition, using the Global Ocean Sampling data set as an example, we demonstrated that the expanded marker database greatly increased the power of metagenomic phylotyping. We incorporated the database into an automated phylogenomic inference application (Phyla-AMPHORA) and made it publicly available. We believe that this centralized resource should have broad applicability in bacterial systematics, phylogenetics, and metagenomic studies.
is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually.
infection (CDI) has high recurrence rate, up ...to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse.
This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles.
The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications.
NCT04305769.
Animals co-evolve with their gut microbiota; the latter can perform complex metabolic reactions that cannot be done independently by the host. Although the importance of gut microbiota has been well ...demonstrated, there is a paucity of research regarding its role in foliage-foraging mammals with a specialized digestive system.
In this study, a 16S rRNA gene survey and metagenomic sequencing were used to characterize genetic diversity and functional capability of cecal microbiota of the folivorous flying squirrel (Petaurista alborufus lena). Phylogenetic compositions of the cecal microbiota derived from 3 flying squirrels were dominated by Firmicutes. Based on end-sequences of fosmid clones from 1 flying squirrel, we inferred that microbial metabolism greatly contributed to intestinal functions, including degradation of carbohydrates, metabolism of proteins, and synthesis of vitamins. Moreover, 33 polysaccharide-degrading enzymes and 2 large genomic fragments containing a series of carbohydrate-associated genes were identified.
Cecal microbiota of the leaf-eating flying squirrel have great metabolic potential for converting diverse plant materials into absorbable nutrients. The present study should serve as the basis for future investigations, using metagenomic approaches to elucidate the intricate mechanisms and interactions between host and gut microbiota of the flying squirrel digestive system, as well as other mammals with similar adaptations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Results of microbial ecology studies using 16S rRNA sequence information can be deceiving due to differences in rRNA operon copy number and genome size of the detected organisms. It therefore will be ...useful for investigators to have a better understanding of how these two parameters differ in various organism types. In this study, the number of ribosomal operons and genome size were separately mapped onto a Bacterial phylogenetic tree.
A representative Bacterial tree was constructed using 31 marker genes found in 578 bacterial genome sequences. Organism names are displayed on the trees using graduations of color such that similar colors indicate similar numbers of operons or genome size. The resulting images provide an intuitive understanding of how copy number and genome size vary in different Bacterial phyla.
Once the phylogenetic position of a novel organism is known the number of rRNA operons, and to a lesser extent the genome size, can be estimated by examination of the colored maps. Further detail can then be obtained for members of relevant taxa from the rrnDB database.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A fourth and large family of lycopene cyclases was identified in photosynthetic prokaryotes. The first member of this family, encoded by the cruA gene of the green sulfur bacterium Chlorobium ...tepidum, was identified in a complementation assay with a lycopene-producing strain of Escherichia coli. Orthologs of cruA are found in all available green sulfur bacterial genomes and in all cyanobacterial genomes that lack genes encoding CrtL- or CrtY-type lycopene cyclases. The cyanobacterium Synechococcus sp. PCC 7002 has two homologs of CruA, denoted CruA and CruP, and both were shown to have lycopene cyclase activity. Although all characterized lycopene cyclases in plants are CrtL-type proteins, genes orthologous to cruP also occur in plant genomes. The CruA- and CruP-type carotenoid cyclases are members of the FixC dehydrogenase superfamily and are distantly related to CrtL- and CrtY-type lycopene cyclases. Identification of these cyclases fills a major gap in the carotenoid biosynthetic pathways of green sulfur bacteria and cyanobacteria.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Amoebae have been considered as a genetic "melting pot" for its symbionts, facilitating genetic exchanges of the bacteria that co-inhabit the same host. To test the "melting pot" hypothesis, we ...analyzed six genomes of amoeba endosymbionts within Rickettsiales, four of which belong to Holosporaceae family and two to Candidatus Midichloriaceae. For the first time, we identified plasmids in obligate amoeba endosymbionts, which suggests conjugation as a potential mechanism for lateral gene transfers (LGTs) that underpin the "melting pot" hypothesis. We found strong evidence of recent LGTs between the Rickettsiales amoeba endosymbionts, suggesting that the LGTs are continuous and ongoing. In addition, comparative genomic and phylogenomic analyses revealed pervasive and recurrent LGTs between Rickettsiales and distantly related amoeba-associated bacteria throughout the Rickettsiales evolution. Many of these exchanged genes are important for amoeba-symbiont interactions, including genes in transport system, antibiotic resistance, stress response, and bacterial virulence, suggesting that LGTs have played important roles in the adaptation of endosymbionts to their intracellular habitats. Surprisingly, we found little evidence of LGTs between amoebae and their bacterial endosymbionts. Our study strongly supports the "melting pot" hypothesis and highlights the role of amoebae in shaping the Rickettsiales evolution.
Early detection of coronavirus disease 2019 (COVID-19) is critical for both initiating appropriate treatment and preventing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ...the causative agent. A simple and rapid diagnostic test that can be performed without any expensive equipment would be valuable for clinicians working in a low-resource setting. Here, we report a point-of-care detection technique for COVID-19 that combines the power of isothermal amplification (reverse transcription helicase-dependent amplification, RT-HDA) and dipstick technologies. The limit of detection of this diagnostic test is six copies of SARS-CoV-2 µl
in clinical specimens. Of the 22 clinical specimens tested, RT-HDA-coupled dipstick correctly identified all positive and negative specimens. The RT-HDA can be performed over a heating block and the results can be interpreted visually with the dipstick technology without any specialized equipment. Furthermore, the RT-HDA-coupled dipstick could be performed in a short turnaround time of ~2 h. Thus, the RT-HDA-coupled dipstick could serve as a point-of-care diagnostic test for COVID-19 in a low-resource environment.
With the explosive growth of bacterial and archaeal sequence data, large-scale phylogenetic analyses present both opportunities and challenges. Here we describe AMPHORA2, an automated phylogenomic ...inference tool that can be used for high-throughput, high-quality genome tree reconstruction and metagenomic phylotyping. Compared with its predecessor, AMPHORA2 has several major enhancements and new functions: it has a greatly expanded phylogenetic marker database and can analyze both bacterial and archaeal sequences; it incorporates probability-based sequence alignment masks that improve the phylogenetic accuracy; it can analyze DNA as well as protein sequences and is more sensitive in marker identification; finally, it is over 100× faster in metagenomic phylotyping.
http://wolbachia.biology.virginia.edu/WuLab/Software.html.
mw4yv@virginia.edu
Supplementary data are available at Bioinformatics online.
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