Project description:Spotted hyena (Crocuta crocuta) is the only extant species of the genus Crocuta, which once occupied a much wider range during the Pliocene and Pleistocene. However, its origin and evolutionary history is somewhat contentious due to discordances being found between morphological, nuclear, and mitochondrial data. Due to the limited molecular data from east Asian Crocuta, and the difficulty of extracting ancient DNA from this area, here we present proteomic analysis of cave hyenas from three locations in northern China. This marks the first proteomic data generated from cave hyenas, adding new molecular data to the east Asian populations. Phylogenetic analysis based on these protein sequences reveals two different groups of cave hyenas in east Asia, one of which could not be distinguished from modern spotted hyenas from northern Africa, tentatively the result of previously suggested gene flow between these lineages. With developments of instrumentation and analytical methods, proteomics holds promising potential for the phylogenetic reconstruction of ancient fauna previously thought to be unreachable using ancient DNA.
Project description:Proteomics using Draft Genomes: a Case Study in Spotted Hyena
Crocuta crocuta, or spotted hyena, are one of four remaining hyena species, notable for its preference for hunting rather than scavenging. Until 2020, no annotated genome had been published for the species; by 2023, three had been published. These bottom-up proteomes, measured in 2020, were used to evaluate the quality of these three genomes for C. crocuta, establishing that the genome annotation featured by UniProt and NCBI lags behind the alternatives in identification sensitivity.
Sample handling and mass spectrometry are detailed in 1330MASS_ANALYTICALREPORT.pdf. Notably, these data were produced with Cys alkylated by MMTS rather than iodoacetamide. The search results come from FragPipe 23, using the "Shao.faa" fasta plus contaminants and decoys.
These shotgun proteomes were collected in roughly three sets. The three "Test" experiments (March and July 2020) established the amount of peptides loaded on column and asked how peptide diverse the samples were. The 13 RPLC experiments (August 2020) represented peripheral, head, abdominal, or thoracic lymph nodes (PL, HL, AL, or TL) from three different animals (571, 572, and 575) plus a few liver and lung samples. The 12 "Fraction" RAWs (September 2020) represent ten bRPLC fractions of a head lymph node pool. See the QuaMeter.tsv table for more details.
These animals are the same as were used for RNA-Seq in NCBI PRJNA658551.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here, we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB dependent pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling (see Snyder-Mackler et al. Science, 2016 doi:10.1126/science.aah3580 and GSE83304). Here we show that, counter to predictions, low status drives more exaggerated expression of both NF-κB and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are not only linked to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history – in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.