Biology subjects

Dick, J. M.

Publications and source records attributed to Dick, J. M..

7 recordsLinked to original sources

bioRxiv2023

Two dimensions of chemical variation of the human microbiome across body sites and in COVID-19 patients

AbstractWater and oxygen availability vary in normal physiology and disease, so evolutionary adjustments of protein sequences to optimally use these chemical resources would represent a competitive advantage for host-associated microbial genomes. In this study, reference proteomes for taxa derived from the Genome Taxonomy Database (GTDB) were combined with 16S rRNA-based taxonomic abundances in order to calculate chemical metrics for community reference proteomes. This permits new insight into community-level genomic adaptation to specific chemical conditions in body sites. Surprisingly, reference proteomes for gut communities appear to be shaped by the physiological function of water absorption in the intestine more than by reducing conditions. Reference proteomes of gut communities in COVID-19 and inflammatory bowel disease (IBD) patients are generally more reduced than controls despite higher relative abundances of aerotolerant organisms and lower abundances of Faecalibacterium and other obligate anaerobes. The trend of chemical reduction in patients is supported by multi-omics (i.e., metagenomic and metaproteomic) data for COVID-19 and can be attributed to relatively oxidized protein sequences for obligate anaerobes compared to aerotolerant genera in gut communities. Genomic adaptation to transiently oxygenated conditions, reflected in more oxidized protein sequences, may be an evolutionary strategy for obligate anaerobes to compete with aerotolerant organisms in the chemical context of gut inflammation. Impact statementHow host-associated microbes (the microbiota) interact with body chemistry is important for understanding the chemical factors that may contribute to diseases. Although COVID-19 and IBD are associated with oxidative conditions in the gut due to inflammation, protein sequences inferred for microbial communities in patients exhibit a trend of chemical reduction rather than oxidation. This implies an evolutionary strategy for obligate anaerobes to more effectively compete with oxygen-tolerant organisms that might otherwise dominate the gut during inflammation. The genomes of organisms in gut communities are distinguished from those in other body sites by proteins with lower hydration state, suggesting that physiological gradients of water availability are a major driver of the evolution of human microbiota.

microbiology↗

bioRxiv2021

Local and global chemical shaping of bacterial communities by redox potential

Thermodynamics predicts a positive correlation between environmental redox potential and oxidation state of molecules; if found for microbial communities it would imply a new kind of deterministic eco-evolutionary process. This study examines evidence for local- and global-scale correlations between oxidation-reduction potential (ORP or Eh) in environmental samples and carbon oxidation state (ZC) of estimated bacterial and archaeal community proteomes. Seventy-nine public datasets for seven environment types (river & seawater, lake & pond, alkaline spring, hot spring, groundwater, sediment, and soil) were analyzed. Taxonomic abundances inferred from high-throughput 16S rRNA gene sequences were combined with NCBI Reference Sequence (RefSeq) proteomes to estimate the amino acid compositions and chemical formulas (CcHhNnOoSs) of community proteomes, which yield ZC. Alkaline hot springs have the lowest ZC for both bacterial and archaeal domains of any environment. Positive global correlations between redox potential and ZC are found for bacterial communities in lake & pond, groundwater, and soil environments, but not archaeal communities, suggesting a broad ecological signal of chemical shaping in Bacteria.

ecology↗

bioRxiv2021

Genomic evidence for a chemical link between redox conditions and microbial community composition

Environmental influences on community structure are often assessed through multivariate analyses in order to relate microbial abundances to separately measured physicochemical variables. However, genes and proteins are themselves chemical entities; in combination with genome databases, differences in microbial abundances directly encode for chemical variability. We predicted that the carbon oxidation state of inferred community proteomes, obtained by combining taxonomic abundances from published 16S rRNA gene sequencing datasets with predicted microbial proteomes from the NCBI Reference Sequence (RefSeq) database, would reflect environmental oxidation-reduction conditions in various natural and engineered settings including shale gas wells. Our analysis confirms the geobiochemical predictions for environmental redox gradients within and between hydrothermal systems and stratified lakes and marine environments. Where they are present, a common set of taxonomic groups (Gamma- and Deltaproteobacteria and Clostridia) act as drivers of the community-level differences in oxidation state, whereas Flavobacteria most often oppose the overall changes. The geobiochemical signal is largest for the steep redox gradients associated with hydrothermal systems and between surface water and produced fluids from shale gas wells, demonstrating the ability to determine the magnitude of redox effects on microbial communities from 16S sequencing alone.

microbiology↗

bioRxiv2021

Redox potential linked to water loss from proteins in evolution and development

Reactions involving water and oxygen are basic features of geological and biological processes. To understand how life interacts with its environment requires monitoring interactions with H2O and O2 at timescales relevant to not only organismal growth but also billions of years of geobiological evolution. Here, chemical transformations intrinsic to evolution and development were characterized by analyzing data from recent phylostratigraphic and proteomic studies. This two-stage analysis involves obtaining chemical metrics (carbon oxidation state and stoichiometric hydration state) from the elemental compositions of proteins followed by modeling the relative stabilities of target proteins against a proteomic background to infer thermodynamic parameters (oxygen fugacity, water activity, and virtual redox potential (Eh)). The main results of this study are a rise in carbon oxidation state of proteins spanning the time of the Great Oxidation Event, a rise in virtual redox potential that coincides with the likely emergence of aerobic metabolism, a rise in carbon oxidation state of proteins inferred from the transcriptome in late stages of Bacillus subtilis biofilm growth, and a drop in stoichiometric hydration state of the fruit fly developmental proteome at the same time as a drop in organismal water content. Stoichiometric hydration state also decreases for proteins with more recent gene ages and through stages of biofilm development, leading to predictions of higher hydration potentials at earlier time points. By building chemical representations of protein evolution and developmental proteomes, exciting new types of geobiochemical proxies can be developed.

biochemistry↗

bioRxiv2020

Water as a reactant in the differential expression of proteins in cancer

How the abundances of proteins are shaped by tumor microenvironments, such as hypoxic conditions and higher water content compared to normal tissues, is an important question for cancer biochemistry. Compositional analysis of more than 250 datasets for differentially expressed proteins compiled from the literature reveals a higher stoichiometric hydration state in multiple cancer types compared to normal tissue; this trend is also evident in pan-cancer transcriptomic and proteomic datasets from The Cancer Genome Atlas and Human Protein Atlas. These findings support the notion of a basic physicochemical link between increased water content in tumors and the patterns of gene and protein expression in cancer. The generally increased hydration state is juxtaposed with a wide spectrum of carbon oxidation states of differentially expressed proteins, which may be associated with different gene ages, host tissue properties and metabolic features of specific cancer types.

biochemistry↗

bioRxiv2020

Distinct trends in chemical composition of proteins from metagenomes in redox and salinity gradients

Thermodynamic influences on the chemical compositions of proteins have remained enigmatic despite much work that demonstrates the impact of environmental conditions on amino acid frequencies. Here, we show that the dehydrating effect of salinity is apparent in protein sequences inferred from metagenomes and metatranscriptomes. The stoichiometric hydration state (nH2O), derived from the number of water molecules in theoretical reactions to form proteins from a particular set of basis species (glutamine, glutamic acid, cysteine, O2, H2O), decreases along salinity gradients including the Baltic Sea, Amazon River and ocean plume, and other samples from freshwater and marine environments. Analysis of other metagenomic datasets shows that differences in carbon oxidation state, rather than stoichiometric hydration state, are a stronger indicator of redox gradients than salinity gradients. These compositional metrics can help to identify thermodynamic effects in the distribution of proteins along chemical gradients at scales from geologic systems to cells.

biochemistry↗

bioRxiv2017

Chemical composition and the potential for proteomic transformation in cancer, hypoxia, and hyperosmotic stress

Models of chemical composition and thermodynamic potential emphasize the microenvironmental context for proteomic transformations. Here, data from 71 comparative proteomics studies were analyzed using elemental ratios and chemical components as measures of oxidation and hydration state. Experimental lowering of oxygen availability (hypoxia) and water activity (hyperosmotic stress) are reflected in decreased oxidation and hydration states of proteomes, but up-expressed proteins in colorectal and pancreatic cancer most often have higher average oxidation or hydration state. Calculations of chemical affinity were used to quantify the thermodynamic potentials for transformation of proteomes as a function of fugacity of O2 and activity of H2O, which serve as scales of oxidation and hydration potential. Potential diagrams for the overall reactions between down- and up-expressed proteins in various datasets have predicted equipotential lines that cluster near unit activity of H2O, suggesting that protein expression is sensitive to local variations in water activity. A redox balance calculation indicates that an increase in the lipid to protein ratio in cancer cells by 20% over hypoxic cells would generate an electron sink of sufficient size for oxidation of the cancer proteomes. These findings demonstrate consistent, condition-dependent chemical differences between proteomes, identify primary microenvironmental constraints on proteomic transformations, and help to quantify the redox balance among cellular macromolecules. The datasets and computer code used here are supplied in a new R package, canprot.

cancer biology↗