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 gradients are consistently associated with variation in health outcomes, including infectious disease. However, distinguishing between social gradients in antigen exposure versus susceptibility remains challenging. Here, we use a nonhuman primate model for chronic social stress to investigate how social status influences the influenza vaccine-induced adaptive immune response. We manipulated the social status of female rhesus macaques to test the response to influenza antigens in naïve individuals and after secondary exposure. Higher social status at the time of first exposure, but not at the time of secondary exposure, predicted stronger antibody responses to both exposures. Social status also drove gene expression differences for adaptive immune pathways, and genes that predict the magnitude of the antibody response overlap with those linked to social status. Thus, social gradients shape the adaptive immune response in a temporally dependent manner, with particular sensitivity at the time of initial antigen exposure.