Dynamic instability of the Major Urinary Protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB101SA, UK.
Genome biology (Impact Factor: 10.81). 02/2008; 9(5):R91. DOI: 10.1186/gb-2008-9-5-r91
Source: PubMed


The major urinary proteins (MUPs) of Mus musculus domesticus are deposited in urine in large quantities, where they bind and release pheromones and also provide an individual 'recognition signal' via their phenotypic polymorphism. Whilst important information about MUP functionality has been gained in recent years, the gene cluster is poorly studied in terms of structure, genic polymorphism and evolution.
We combine targeted sequencing, manual genome annotation and phylogenetic analysis to compare the Mup clusters of C57BL/6J and 129 strains of mice. We describe organizational heterogeneity within both clusters: a central array of cassettes containing Mup genes highly similar at the protein level, flanked by regions containing Mup genes displaying significantly elevated divergence. Observed genomic rearrangements in all regions have likely been mediated by endogenous retroviral elements. Mup loci with coding sequences that differ between the strains are identified--including a gene/pseudogene pair--suggesting that these inbred lineages exhibit variation that exists in wild populations. We have characterized the distinct MUP profiles in the urine of both strains by mass spectrometry. The total MUP phenotype data is reconciled with our genomic sequence data, matching all proteins identified in urine to annotated genes.
Our observations indicate that the MUP phenotypic polymorphism observed in wild populations results from a combination of Mup gene turnover coupled with currently unidentified mechanisms regulating gene expression patterns. We propose that the structural heterogeneity described within the cluster reflects functional divergence within the Mup gene family.

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Available from: Rob Beynon, Oct 04, 2015
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    • "All are synthesised as preproteins , but the signal peptide is removed precisely to reveal a conserved N-terminus. Mouse MUPs contain a single disulphide bond but only two have consensus sites for N-linked glycosylation (MUP3 and MUP21) of which one has been proven to be glycosylated [3]. Of these 21 genes, the central 15 show very high sequence homology, and the peripheral six are more variable in their sequence. "
    • "Further separation of the high molecular weight fraction by anion exchange chromatography revealed that attraction was elicited by a single subfraction. We showed that the active component in this subfraction was a single atypical urinary MUP (MGI:3651981, Mup20) expressed only by males and encoded by a gene in the peripheral region of the Mup gene cluster where there is considerable divergence between Mup genes (Mudge et al., 2008; who referred to this as Mup gene 17 using a different numbering scheme from MGI). This MUP is responsible for binding most of the male-specific urinary volatile pheromone 2-sec-butyl-4,5-dihy- drothiazole (Armstrong et al., 2005), which is known to stimulate receptors in the vomeronasal organ with high sensitivity (Leinders- Zufall et al., 2000). "
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    ABSTRACT: Many territorial mammals invest heavily in competitive scent marks that advertise their location, identity and current social and physiological status. Here we review the behavioural and molecular components of scent marking in house mice, Mus musculus domesticus, that influence female attraction to males and discuss how pheromone-induced learning among females and differential scent investment among males both influence female attraction to specific scent owners. Although mouse urine scents contain numerous sex-specific and individual-specific components, female attraction to spend more time near urine from males depends on contact with an involatile protein pheromone, darcin. This is an atypical major urinary protein (MUP) expressed only by males. On contact, this pheromone acts as a highly potent stimulus for associative learning, such that females learn similar attraction to the individual male's airborne odour associated with darcin; they also learn attraction to spatial cues where the pheromone was encountered. This targets female attraction to both the odour and location of individual male scent mark owners. However, the concentration and quality of airborne volatiles emitted from scent marks influence approach and contact with male scents. Under competitive pressure, males invest heavily in refreshment of scent marks at a high rate and deposit a high concentration of MUPs that bind urinary volatiles and extend the duration of volatile release. Females also gain information from airborne volatiles, including the social and infection status of the owner, which can alter their attraction to contact his scent. The ability of females to learn about individual males from their scent marks means that most decisions about preferred males are likely to be made before females are ready to mate. We are just starting to understand how different information in male scents is integrated in making these decisions.
    Animal Behaviour 11/2014; 97. DOI:10.1016/j.anbehav.2014.08.010 · 3.14 Impact Factor
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    • "But pheromone signatures differ greatly among mouse family groups, and are thought to constitute a very powerful reproductive isolating mechanism – even within one subspecies , and even within small geographic localities and between demes (Mudge et al. 2008). Differences in pheromone signatures between subspecies are pronounced, for example in vomeronasal genes (Del Punta et al. 2000; Teeter et al. 2008) and MUP (major urinary protein) profiles (Mudge et al. 2008), and these presumably contribute to reproductive isolation. "
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    ABSTRACT: The house mouse, Mus musculus, was first introduced into New Zealand in significant numbers in the early to mid nineteenth century, with genomic components from different sources of the three subspecies M. m. domesticus, M. m. musculus and M. m. castaneus. M. m. domesticus is now widely distributed in New Zealand, with genomic and morphological evidence of M. m. musculus in a few scattered locations. M.m.domesticus/M.m.castaneus hybrids are dominant in the southern third of the South Island. We anticipated that there should be a definable southern contact zone between pure M. m domesticus and M.m.domesticus/M.m.castaneus hybrids. We tested this hypothesis by screening 170 DNA samples from mice collected in the southern South Island, using a PCR technique which rapidly distinguishes the mitochondrial genomes of the three subspecies. All mice sampled from in or north of Lincoln (43.63oS) had only M. m. domesticus mtDNA, whereas all those from or further south than Hook (44.68 oS) had M. m. castaneus mtDNA. Between the two sites, mice carrying mtDNA of both subspecies were found, sometimes in the same building. On present data, this contact zone extends approximately 50 km north to south and some 30 km inland. Classical tests with three nuclear DNA markers confirmed earlier work showing that the nuclear genomes of all mice appeared to be predominantly domesticus-like. We conclude that if purebred M. m. castaneus mice did originally reach New Zealand, extensive backcrossing with M. m. domesticus has made the castaneus nuclear genome virtually undetectable with the tests that we employ.
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