Biology subjects

Rizvi, S. M.

Publications and source records attributed to Rizvi, S. M..

3 recordsLinked to original sources

bioRxiv2021

Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells

Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Studies to date suggest that non-lesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA-sequencing and spatial-seq. We demonstrate that normal-appearing skin of lupus patients represents a type I interferon-rich, prelesional environment that skews gene transcription in all major skin cell types and dramatically distorts cell-cell communication. Further, we show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining pro-inflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and non-lesional skin in lupus and identify a role for skin education of CD16+ dendritic cells in CLE pathogenesis.

immunology↗

bioRxiv2021

Computational analysis of vertebrate myoglobins reveals aggregation resistance in aquatic birds and higher surface hydrophobicity in fish

Myoglobin is the major oxygen carrying protein of vertebrate muscle, and high myoglobin net charge is known to hold evolutionary significance as a molecular signature of secondarily aquatic diving capacity in mammals. However, the evolution of myoglobins electrostatic properties in non-mammalian vertebrates, such as birds, has not been investigated. Here, we used a new deep learning-based protein folding algorithm to model the tertiary structures of myoglobin from 302 vertebrate species and performed a comparative analysis of their net charge, positively charged solvent-accessible surface area, and negatively charged solvent-accessible surface area. For avian myoglobins, we also calculated selection pressure ({omega}). The results suggest that the myoglobins of diving avians, specifically those of the penguins (Sphenisciformes) and diving ducks (Aythyini), have highly positively charged electrostatic surfaces, which evolved via positive selection to reduce aggregation propensity and allow greater storage of oxygen for extended underwater foraging. In contrast, galliform myoglobins are under high purifying selection. Distribution of charged atoms on myoglobin surface was more indicative of high myoglobin content than net charge. We also found inter-class differences in net charge; bird myoglobins are the most positively charged and reptile and amphibian myoglobins are the most negatively charged, and net charge seems to be negatively associated with herbivory within mammals. Finally, we propose an equation that describes the relationship between myoglobin net charge and concentration better than the previously suggested logarithmic function. Our findings offer novel insights into the diversification of myoglobin in vertebrate clades and highlight the power of computational structural approaches for zoological and evolutionary research.

bioinformatics↗

bioRxiv2020

Gut Fungi Possess a Conserved Toxin Immunity Gene of Bacterial Origin

Prokaryotes and some unicellular eukaryotes routinely overcome evolutionary pressures with the help of horizontally acquired genes. In contrast, it is unusual for multicellular eukaryotes to adapt through horizontal gene transfer (HGT). Recent studies identified several cases of adaptive acquisition in the gut-dwelling multicellular fungal phylum Neocallimastigomycota. Here, we add to these cases the acquisition of a putative bacterial toxin immunity gene, PoNi, by an ancient common ancestor of four extant Neocallimastigomycota genera through HGT from an extracellular Ruminococcus bacterium. The PoNi homologs in these fungal genera share extraordinarily high (>70%) amino acid sequence identity with their bacterial donor xenolog, providing definitive evidence of HGT as opposed to lineage-specific gene retention. Furthermore, PoNi genes are nested on native sections of chromosomal DNA in multiple fungal genomes and are also found in polyadenylated fungal transcriptomes, confirming that these genes are authentic fungal genomic regions rather than sequencing artifacts from bacterial contamination. The HGT event, which is estimated to have occurred at least 66 ({+/-}10) million years ago in the gut of a Cretaceous mammal, gave the fungi a putative toxin immunity protein (PoNi) which likely helps them survive toxin-mediated attacks by bacterial competitors in the mammalian gut microbiome. SignificanceAdaptation via horizontal gene transfer (HGT) is uncommon in multicellular eukaryotes. Here, we report another bona fide case of adaptive evolution involving the horizontal transfer of a bacterial toxin immunity gene from extracellular Ruminococcus bacteria to gut-dwelling multicellular fungi. The acquired gene may help the fungi compete against bacterial neighbors in the gut.

ecology↗