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Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

ABSTRACT: House mice (Mus musculus) produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This 'barcode hypothesis' requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild-caught house mice from eight populations using isoelectric focusing. We found that MUP profiles of wild male house mice are not individually unique, and though they were highly variable, closer inspection revealed that the variation strongly depended on MUP band type. The prominent ('major) bands were surprisingly homogenous (and hence most MUPs are not polymorphic), but we also found inconspicuous ('minor') bands that were highly variable and therefore potential candidates for individual fingerprints. We also examined changes in urinary MUP profiles of 58 males over time (from 6 to 24 weeks of age), and found that individual MUP profiles and MUP concentration were surprisingly dynamic, and showed significant changes after puberty and during adulthood. Contrary to what we expected, however, the minor bands were the most variable over time, thus no good candidates for individual fingerprints. Although MUP profiles do not provide individual fingerprints, we found that MUP profiles were more similar among siblings than non-kin despite considerable fluctuation. Our findings show that MUP profiles are not highly stable over time, they do not show strong individual clustering, and thus challenge the barcode hypothesis. Within-individual dynamics of MUP profiles indicate a different function of MUPs in individual recognition than previously assumed and advocate an alternative hypothesis ('dynamic changes' hypothesis).

SUBMITTER: Thoß M

PROVIDER: S-EPMC4783862 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

Thoß M M Luzynski K C KC Ante M M Miller I I Penn D J DJ

Frontiers in ecology and evolution 20150601

House mice (<i>Mus musculus)</i> produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This 'barcode hypothesis' requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild- ...[more]

PMID: 26973837

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Project description:BackgroundReliable recognition of individuals requires phenotypic identity signatures that are both individually distinctive and appropriately stable over time. Individual-specific vocalisations or visual patterning are well documented among birds and some mammals, whilst odours play a key role in social recognition across many vertebrates and invertebrates. Less well understood, though, is whether individuals are recognised through variation in cues that arise incidentally from a wide variety of genetic and non-genetic differences between individuals, or whether animals evolve distinctive polymorphic signals to advertise identity reliably. As a bioassay to understand the derivation of individual-specific odour signatures, we use female attraction to the individual odours of male house mice (Mus musculus domesticus), learned on contact with a male's scent marks.ResultsLearned volatile odour signatures are determined predominantly by individual differences in involatile major urinary protein (MUP) signatures, a specialised set of communication proteins that mice secrete in their urine. Recognition of odour signatures in genetically distinct mice depended on differences in individual MUP genotype. Direct manipulation using recombinant MUPs confirmed predictable changes in volatile signature recognition according to the degree of matching between MUP profiles and the learned urine template. Both the relative amount of the male-specific MUP pheromone darcin, which induces odour learning, and other MUP isoforms influenced learned odour signatures. By contrast, odour recognition was not significantly influenced by individual major histocompatibility complex genotype. MUP profiles shape volatile odour signatures through isoform-specific differences in binding and release of urinary volatiles from scent deposits, such that volatile signatures were recognised from the urinary protein fraction alone. Manipulation using recombinant MUPs led to quantitative changes in the release of known MUP ligands from scent deposits, with MUP-specific and volatile-specific effects.ConclusionsDespite assumptions that many genes contribute to odours that can be used to recognise individuals, mice have evolved a polymorphic combinatorial MUP signature that shapes distinctive volatile signatures in their scent. Such specific signals may be more prevalent within complex body odours than previously realised, contributing to the evolution of phenotypic diversity within species. However, differences in selection may also result in species-specific constraints on the ability to recognise individuals through complex body scents.

Project description:The gut microbiota is shaped by host metabolism. In house mice (Mus musculus), major urinary protein (MUP) pheromone production represents a considerable energy investment, particularly in sexually mature males. Deletion of the Mup gene family shifts mouse metabolism toward an anabolic state, marked by lipogenesis, lipid accumulation, and body mass increases. Given the metabolic implications of MUPs, they may also influence the gut microbiota. Here, we investigated the effect of a deletion of the Mup gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wild-type and knockout males but not females. Deletion of the Mup gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, a species of Ruminococcaceae and several microbial functions, such as transporters involved in vitamin B5 acquisition, were significantly depleted in the microbiota of Mup knockout males. Altogether, these results show that MUPs significantly affect the gut microbiota of house mouse in a sex-specific manner.IMPORTANCEThe community of microorganisms that inhabits the gastrointestinal tract can have profound effects on host phenotypes. The gut microbiota is in turn shaped by host genes, including those involved with host metabolism. In adult male house mice, expression of the major urinary protein (Mup) gene cluster represents a substantial energy investment, and deletion of the Mup gene family leads to fat accumulation and weight gain in males. We show that deleting Mup genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional compositions. Male mice without Mup genes harbored fewer gut bacterial families and reduced abundance of a species of Ruminococcaceae, a family that has been previously shown to reduce obesity risk. Studying the impact of the Mup gene family on the gut microbiota has the potential to reveal the ways in which these genes affect host phenotypes.

Project description:BackgroundThere is a need for novel fluid biomarkers tracking neuroinflammatory responses in Alzheimer's disease (AD). Our recent cerebrospinal fluid (CSF) proteomics study revealed that migration inhibitory factor (MIF) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1) increased along the AD continuum. We aimed to assess the potential use of these proteins, in addition to sTREM2, as CSF biomarkers to monitor inflammatory processes in AD.MethodsWe included cognitively unimpaired controls (n = 67, 63 ± 9 years, 24% females, all amyloid negative), patients with mild cognitive impairment (MCI; n = 92, 65 ± 7 years, 47% females, 65% amyloid positive), AD (n = 38, 67 ± 6 years, 8% females, all amyloid positive), and DLB (n = 50, 67 ± 6 years, 5% females, 54% amyloid positive). MIF, sTREM1, and sTREM2 levels were measured by validated immunoassays. Differences in protein levels between groups were tested with analysis of covariance (corrected for age and sex). Spearman correlation analysis was performed to evaluate the association between these neuroinflammatory markers with AD-CSF biomarkers (Aβ42, tTau, pTau) and mini-mental state examination (MMSE) scores.ResultsMIF levels were increased in MCI (p < 0.01), AD (p < 0.05), and DLB (p > 0.05) compared to controls. Levels of sTREM1 were specifically increased in AD compared to controls (p < 0.01), MCI (p < 0.05), and DLB patients (p > 0.05), while sTREM2 levels were increased specifically in MCI compared to all other groups (all p < 0.001). Neuroinflammatory proteins were highly correlated with CSF pTau levels (MIF: all groups; sTREM1: MCI, AD and DLB; sTREM2: controls, MCI and DLB). Correlations with MMSE scores were observed in specific clinical groups (MIF in controls, sTREM1 in AD, and sTREM2 in DLB).ConclusionInflammatory-related proteins show diverse expression profiles along different AD stages, with increased protein levels in the MCI stage (MIF and sTREM2) and AD stage (MIF and sTREM1). The associations of these inflammatory markers primarily with CSF pTau levels indicate an intertwined relationship between tau pathology and inflammation. These neuroinflammatory markers might be useful in clinical trials to capture dynamics in inflammatory responses or monitor drug-target engagement of inflammatory modulators.

Dataset Information

Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

Publications

Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

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