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Relationships between immune gene expression and circulating cytokine levels in wild house mice

ABSTRACT: Abstract Quantitative PCR (qPCR) has been commonly used to measure gene expression in a number of research contexts, but the measured RNA concentrations do not always represent the concentrations of active proteins which they encode. This can be due to transcriptional regulation or post?translational modifications, or localization of immune environments, as can occur during infection. However, in studies using free?living non?model species, such as in ecoimmunological research, qPCR may be the only available option to measure a parameter of interest, and so understanding the quantitative link between gene expression and associated effector protein levels is vital. Here, we use qPCR to measure concentrations of RNA from mesenteric lymph node (MLN) and spleen tissue, and multiplex ELISA of blood serum to measure circulating cytokine concentrations in a wild population of a model species, Mus musculus domesticus. Few significant correlations were found between gene expression levels and circulating cytokines of the same immune genes or proteins, or related functional groups. Where significant correlations were observed, these were most frequently within the measured tissue (i.e., the expression levels of genes measured from spleen tissue were more likely to correlate with each other rather than with genes measured from MLN tissue, or with cytokine concentrations measured from blood). Potential reasons for discrepancies between measures including differences in decay rates and transcriptional regulation networks are discussed. We highlight the relative usefulness of different measures under different research questions and consider what might be inferred from immune assays. In wild house mice, there is little correlation between immune gene expression and final proteins. This is important to consider in future ecoimmunology research.

SUBMITTER: Young S

PROVIDER: S-EPMC7771139 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundThrough human-aided dispersal over the last ~ 10,000 years, house mice (Mus musculus) have recently colonized diverse habitats across the globe, promoting the emergence of new traits that confer adaptive advantages in distinct environments. Despite their status as the premier mammalian model system, the impact of this demographic and selective history on the global patterning of disease-relevant trait variation in wild mouse populations is poorly understood.ResultsHere, we leveraged 154 whole-genome sequences from diverse wild house mouse populations to survey the geographic organization of functional variation and systematically identify signals of positive selection. We show that a significant proportion of wild mouse variation is private to single populations, including numerous predicted functional alleles. In addition, we report strong signals of positive selection at many genes associated with both complex and Mendelian diseases in humans. Notably, we detect a significant excess of selection signals at disease-associated genes relative to null expectations, pointing to the important role of adaptation in shaping the landscape of functional variation in wild mouse populations. We also uncover strong signals of selection at multiple genes involved in starch digestion, including Mgam and Amy1. We speculate that the successful emergence of the human-mouse commensalism may have been facilitated, in part, by dietary adaptations at these loci. Finally, our work uncovers multiple cryptic structural variants that manifest as putative signals of positive selection, highlighting an important and under-appreciated source of false-positive signals in genome-wide selection scans.ConclusionsOverall, our findings highlight the role of adaptation in shaping wild mouse genetic variation at human disease-associated genes. Our work also highlights the biomedical relevance of wild mouse genetic diversity and underscores the potential for targeted sampling of mice from specific populations as a strategy for developing effective new mouse models of both rare and common human diseases.

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Relationships between immune gene expression and circulating cytokine levels in wild house mice

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